Welcome to the huberman Lab podcast, where we discuss science and science based tools for everyday life.
I'm Andrew huberman and I'm a professor of
neurobiology and Ophthalmology at Stanford school of
medicine. Today, we're discussing alcohol, one of the most commonly consumed substances
on the planet Earth.
She mentioned that both humans and non-human
animals, consume alcohol either for
recreational purposes
because they like the feeling that
it gives them or
Additional purposes or for other purposes that will discuss. We are. Of course, going to discuss the
effects of alcohol on our
biology ranging, from its effects on individual cells, on organs and organ
systems in our brain and body.
We are also going to discuss
the effects of the effects of alcohol.
That is what being inebriated really does to our thinking
in our behavior and how it does it.
And we are going to address what seems to be one of the more common questions out there which is whether or not low to moderate amounts of drinking are better for our
Health than
zero, alcohol consumption at
all. And of course, we will talk about severe
alcohol intake binge drinking. We will also talk
about hangover and what science says about ways to reduce the effects of Hangover, either. By doing things that are in ocula Tory, meaning before you drink, or while you
drink as well as things to do, if you happen to
have a hangover, we will discuss some of the genetic differences for
alcohol and
alcoholism and we will discuss alcohol consumption in
Young people,
and how that can be, especially detrimental for
reasons that I think are going to be quite surprising to most of you. My goal is that, by the end of today's episode, you will have a thorough understanding
of what alcohol does to your brain and body, and that you will be able
to make informed decisions as to whether or
not, you should be consuming zero, absolutely no alcohol small to moderate amounts of alcohol. Again, will Define exactly what that means small to moderate
amounts. And if you or somebody else that, you know, is consuming excessive amounts of alcohol.
All
that are clearly detrimental to your
health. Some of the better routes and
resources that you can use in order to remove that dependence and or consumption, I'd like to preface all of that
by saying that today's discussion is really geared toward giving you information. It is not
about judging alcohol intake, or lack of alcohol intake. I just want you to be able to make the most informed decision about alcohol
possible. I'm pleased to announce that the human Lab podcast is now partnered with Momentis supplements. We partnered with
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And remove things from your protocol in a way. That's really systematic and scientific. If you'd like to see the supplements that we partner with Momentis on. You can go to live momentous.com huberman there. You'll see those supplements and just keep in mind that we are constantly expanding the library of supplements available through momentous on a regular basis. Again that's live momentous.com huberman. Before we get in today's content in detail, I just want to answer a commonly asked, question about alcohol
consumption and the brain and
the question that so often comes up is whether or not
Low to moderate amounts of
alcohol. Maybe one drink a day or one or
two drinks a day kind of thing whether or not that is bad for your brain in particular, whether or not it causes
degeneration of neurons or nerve cells.
Now, the reason that question comes up so
often is
because for many years it's been known
that high levels of alcohol consumption. So 12 to 24 drinks per week. Or more is
certainly causing
neurodegeneration in particular
of the so called Neo cortex.
The outer layers of the brain. That how is associative?
Memories that house our ability to think and plan that house our ability to
regulate our more primitive
drives according to context, Etc.
So to make very clear drinking a lot. So having, you know, three or four drinks per night. Every night of the week, is clearly bad for the brain, a recent study. However, finally address the question of whether or not low
to moderate amounts of alcohol, consumption can cause brain
degeneration, the title of the study,
Is associations between alcohol consumption and gray and white matter
volumes in the UK biobank the United Kingdom Bayou Bank. First of all.
Gray matter are the neurons that is the so-called cell bodies that would house the Genome of the cells Etc. And white
matter is the connections, the fibers, the so called axons of neurons and it's called white matter because that that tissue is surrounded by a fatty tissue called myelin, which allows nerve cells to communicate with each other very quickly. So,
what this study did is it looked at the
Means both the gray matter and the white matter of more than 30,000 any more than 35,000 generally healthy middle-aged and older adults in the United Kingdom who were drinking various amounts of alcohol. What they found was that even for people that were drinking low to moderate amounts of alcohol. So one or two drinks per day.
There was evidence of thinning of the
neocortex. So loss of neurons in the
neocortex and other brain regions. And I don't say this in order to cause alarm, I tell you this, because they are important data because they reveal and indeed answer the question that has been burning for so long, as to whether or not chronic alcohol intake can disrupt the brain even if the chronic intake is
very low. Now, we should talk
about what the word chronic means because many people when they hear the word chronic think
hi.
Levels of whatever intake. Okay, so they think five drinks a night or ten drinks a night or
people drinking every night. Now, in this study, they looked at people who on average were drinking one or two drinks per night, so that could be 14 drinks on the weekend. It could be one drink per night. It could be seven drinks on Friday in other words on average one or two drinks per
night. And I think many people out there are drinking somewhere between one and two drinks per night or
Day of the week on average, so that would be 7 to 14 drinks per week.
So, this is an important study because it says that if you're consuming even just seven glasses of wine across the week, it's likely that there is going to be some
degeneration of your brain, in response to that alcohol intake. Although, as mentioned earlier, we will talk about some of the things that can inoculate against some of that neuronal
loss. For those of you that are interested in reading the study in more
detail, we put a link to it in the show. No captions. Before we begin.
Like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is however, part of my desire and
effort to bring zero cost to Consumer
information about science and science related tools to the general public in keeping with that theme. I'd like to thank the sponsors of today's
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Let's talk about alcohol and let's just acknowledge that human beings have been
consuming alcohol for thousands of years.
If you look at the archaeological,
It's from Mesopotamia. You'll find that
five thousand years ago. People had wine vessels or if you
want to know. When people first started distilling alcohol,
what should people surprised that did not first take place in Ireland? And that's not a joke about the Irish. That you'll see a lot of claims online that the Irish were the first to distill alcohol. But in fact, they were not, it was the
Chinese that were the first to
distill alcohol, and that took place in China in the first century.
Alcohol has been used for nutritional purposes. So there are cultures that
believe in indeed, still believe
that the calories and alcohol are
Useful. Although
later we'll talk about how alcohol calories are indeed, empty calories and what an empty calorie really is why it's called empty
alcohol has been used for medicinal purposes
because indeed it does kill
bacteria and as you'll soon find out the fact that it kills bacteria because that is absolutely true. It also kills the good bacteria in your gut and the destruction of that good bacteria in your gut
can lead to things like leaky
gut syndrome and has all sorts of issues and their ways to deal with those issues and we'll talk about those. So alcohol has been used for medicinal purposes. It's been used.
Clean surfaces, it's used in my laboratory in order to make up so-called reagents to do our experiments. But most humans have been consuming
alcohol in order to change their internal state, in order to feel differently than they would, otherwise
that feeling of being drunk, or inebriated or Tipsy or lightheaded is something that many, not all, but many humans seem to enjoy and pursue even though,
Typically it leads to a feeling of being less, happy
less motivated, more stressed at cetera when the alcohol wears
off, that's pretty incredible, right? I mean we're talking about a substance that people are been highly motivated to pursue that are
still highly motivated to
pursue to create and to consume that they'll spend money on and that's despite the fact that it makes them feel good and then it makes them feel lousy. Now, some of you might be saying, well, I drink, but I don't drink to excess and therefore I don't feel lousy
If you're good, when I drank and then it wears off and it allows me get through my evening and then the next morning, I'm ready to go.
Okay. That very well may be true. I believe those people. And as I mentioned the beginning of the episode, I'm not here to
demonize alcohol in any
way, but I do want to point out what
alcohol is and how it creates the effects that it
does. And then I want to talk about what those effects are. When you engage in consuming alcohol, even as often as one or two nights per week or
Let's say you're just somebody who has a drink or two on Friday, maybe a few more on Saturday or maybe you're somebody. Who consumes all your alcohol. One night per week or one night per month.
We'll talk about how that's affecting your biology.
So let's address what alcohol is and how it affects the cells and tissues and organs of your body. Then we'll take a look at some of the epidemiology that is how many people are consuming alcohol and how much they're drinking and then you will be able. I think to get a good sense of how the alcohol
that you're drinking. If you're drinking any of it at all, is
impacting your
In body and the choices. You might want to make about how and when to drink alcohol or even if you want to eliminate alcohol altogether,
okay? So some basic
chemistry and biology of alcohol. And again, I'll make this very clear even if you don't have a chemistry in biology background because of the
structure of alcohol it is what's called both water soluble and fat soluble translated into what's meaningful for you. What that means is when you drink alcohol it can pass into all the cells
and tissues of your body. It has
has no trouble just passing right into those cells.
So unlike a lot of substances and
drugs that actually attached to the surface of cells to receptors as they're called Low parking spots
and then trigger a bunch of down streams, like Domino Cascades of effects. Alcohol actually has its own Direct
effects on cells because it can really just pass into those cells.
So it's water and fat soluble and the fact that it can pass into so many organs
and cells, so easily is really what explains its
Imaging effects,
as you mentioned that, there are three main types of alcohol.
There's
isopropyl methyl, and ethyl alcohol, and only the last one.
Ethyl alcohol or ethanol is fit for human consumption. However
it is still toxic okay it produces
substantial stress and damage to cells.
I'd love to be able to tell you otherwise but that's just a fact ethanol produces substantial damage to cells and it does that because when you ingest
ethanol,
it
has to be converted into something else because it is toxic to the body and there's a
molecule inside of all of us called NAD. And you may have heard of NAD because it's quite popular. There's a lot of discussion about NAD
in the longevity literature right now and AD is present in all our cells from birth until death.
The levels of NAD tend to go down across the lifespan, their ideas that
increasing levels of NAD. May extend lifespan, a lot of that is still controversial or at least
we should say is
ongoing in terms of the research. But nonetheless, when you ingest ethanol,
D and related biochemical pathways are involved in converting that ethanol into something called acetaldehyde. It's broken down into acetaldehyde. And if you thought ethanol was bad, acetaldehyde is particularly bad as he do aldehyde is poison, it will kill cells, it damages and kill cells and is in discriminant
as to, which sells it damages and kills
now, that's a problem obviously, and the body deals with that problem by using another component
of the NAD
biochemical.
Way to convert a seal aldehyde into something, called acetate acetate is actually something
that your body can use as fuel
and that process of going from ethanol to acetaldehyde to acetic. 8 does involve the production of a
toxic molecule, right again, acetaldehyde is really
toxic and NAD and it we want to get technical at
the NAD to nadh ratio and that
chemical step is the rate limiting step to f.
His metabolism. What does that mean for you? What that means
is that if your body can't do this conversion of ethanol to
acetaldehyde to acetic, eight fast enough, well acetaldehyde will build up in your body and cause more damage. So it's
important that your body be able to do this
conversion very quickly and the place where it does that is within the liver and
cells within the liver are
very good at this conversion process, but they are cells and they are exposed to this Eagle aldehyde in the
Version process and so cells within the liver, really take a beating in the alcohol metabolism events. So
the key thing to understand here is that when you
ingest alcohol, you are, yes ingesting. A poison and that poison is converted into an even
worse. Poison in your body and some percentage of that worse poison is converted into a form of
calories that you can use to generate energy generate ATP. And the reason why alcohol is considered empty calories is because that entire process is very metabolically.
Costly. But there's no real
nutritive value of the calories that it
creates, you can use it for immediate energy, but it can't be stored in any kind of meaningful or beneficial way. It doesn't provide any vitamins. It doesn't
provide any amino acids. It doesn't provide any fatty acids. It's truly, empty calories. I
know some people talk about sugar is empty calories, but sugar actually is a far better fuel source
than alcohol or
acetate. But nonetheless, when you ingest
alcohol, some percentages being shuttled into
to a worse
poison and some is being shuttled into a fuel source. Now, the important thing to understand is that it is the poison,
the acetaldehyde itself that leads to the effect of being inebriated or drunk. I
think most people don't realize that that being drunk is actually a poison induced disruption in the way that your neural circuits work and so we should ask ourselves at which neural circuits. What brain areas, what body are is
involved in feeling drunk or inebriated.
When thinking about this state of being tipsy or happier really drunk or a little bit drunk, I want to mention something I think most people aren't aware of. And that's the fact that for people that are regular drinkers or that have our genetic predisposition to
alcoholism.
When they drink, they tend to feel
very energized and very good for longer periods of time.
Again, people have a genetic predisposition to alcohol or people who are chronic drinkers or even just if you recall chronic
Doesn't have to mean a ton of alcohol, but they're
drinking one or two per night or there every other night type drinkers, or Thursday, through Sunday
drinkers. Those people typically experienced an increase in alertness and mood, when they drink,
whereas occasional drinkers
will have a briefer, meaning less long-lasting period of feeling good when they drank. And then more quickly transition into a state in which they're tired, or they start losing motor skills. They start slurring their speech.
I also want to emphasize this as distinct from tolerance, will talk about tolerance later in exactly what tolerance means but I really want to highlight the fact that when people ingest this poison because indeed it is Poison, the range of effects is very different and you can reliably predict who are the people with a predisposition to alcoholism and who are the people who are more regular drinkers by the Contour, the timing of the different effects. And again people who tend to feel more alert and excited
Every time they drink, they tend to get a real lift. They be coming on the
life of the party and that lasts a long while.
Those people are the ones that really have to be careful
about predisposition for alcoholism. And those people also need to be careful about that.
You're drinking in the amount of
drinking that they're doing, even if they're not full-blown alcoholics now. Of course, people who are ingesting alcohol, who are not accustomed to drink, alcohol have to be concerned about drink alcohol, for other reasons because it can impair motor function and judgment etcetera.
But in thinking about the biochemical effects of alcohol, what it's doing to the body, what it's doing in all cases, is it's consumed into the gut, right? Goes into the stomach, the liver immediately starts. This
conversion that we talked about before of ethanol to acetaldehyde to acetic eight and some amount of acetaldehyde and acetate are making it into the brain. It crosses the blood-brain barrier.
Again, the brain has this fence around it that we call the blood-brain barrier or the BBB many things, most things thankfully can't pass across the blood-brain barrier.
But alcohol because it's water and fat soluble
just cruises right
across this fence. And into the milieu, the environment
of the brain which is made up of a couple different major cell types neurons nerve cells, and Soco glial cells, which are in between the nerve cells will talk about the effects on each of those soon.
So what happens when alcohol gets into the brain? That makes us feel Tipsy. You're drunk and in some people makes
people feel really especially energized and happy. Well,
alcohol is in discriminant in terms of which brain areas.
Areas it goes to again, it doesn't bind a particular receptors,
but it does seem to have a
propensity or an
affinity for a particular, brain areas that are involved in certain
kinds of thinking, and behavior.
So, one of the first things that happens is that there's a slight, at
least, after the first drink, or second drink. There's a slight
suppression in the activity of neurons. In the prefrontal cortex. This is an area of your neocortex, that's involved in thinking and planning, and perhaps above all and suppression.
Of impulsive behavior. So if you go to a
party and they're serving alcohol and people are consuming drinks, what you'll notice is that a few minutes into that party, the volume
of people's voices will increase, and that's because
people are simply not paying attention to their voice modulation
as other people. Start speaking more loudly, other people are speaking more loudly. We've all had this experience, right? Of going to a party and then you step outside for a moment ago. Oh, my goodness. Our shouting, you come up with next day, you got a sore throat, might be that you picked up some sort of bug, some virus or
something. But
oftentimes it's just the fact
I've been shouting all night just to be heard
because as the prefrontal cortex shuts
down people stop modulating their their level of speech. Quite, as much
also, notice that people start gesticulating more, people start standing up and sitting down more, the start walking around more. If there's music on people, might spontaneously start dancing. All of this is because these areas of the, prefrontal cortex normally are providing, what's called top-down inhibition, they are releasing a neurotransmitter called Gaba
on to various parts of the brain are involved in impulsive motor.
And thought patterns and as you shut down the, prefrontal cortex that gabaergic
suppression of impulses
starts to be released. So people will say things that they want to say without so much for
thought about what they're saying, or they might do things that they want to do
without really thinking it through quite as much, or they might not even remember
thinking it through it all or experience, I should say, thinking it through it. All we haven't talked about blacking out yet in the effects of alcohol on memory, but as long as we're there, I'll just tell you that alcohol has a
very strong effect.
Act in suppressing the neural networks that are involved in memory formation and storage. This is why oftentimes we forget the events of a night out if we've been drinking.
One of the more important things to know about the effects of alcohol in the brain is this disruption in top-down inhibition, but also that areas of the brain that are involved in flexible Behavior. So if considering
different options, like, I could do a, or I could do be, I could say this to that markets, say that I could say,
to not way or I could say it in this way.
This might be a little more tactful those brain areas basically
shut down
entirely and people just tend to say what they want to say. So the key thing to understand is that when people drink the prefrontal cortex and top-down inhibition is diminished, that is Habitual
behavior and impulsive behavior starts to increase. Now, what's interesting is, this is true in the short term. So after people have one or two, maybe three or four drinks, but it's
also true that the more often that people
Drink there are changes in the very circuits that underlie
habitual and impulsive behavior.
This is really important to highlight so much so that I want to drill into
it a little bit more deeply
for the person that drinks, say, every Thursday night, or every Friday night, or goes out only on Saturdays, but every Saturday there's evidence that there are changes in the neural circuits of the brain that control habitual
behavior, and impulsive behavior,
and they are modified and strengthened in ways that
Those people more habitual and more impulsive
outside the times in which they are
drinking. And when they drink, impulsive and habitual Behavior, tends to increase even further, this is something that's not often talked about when discussing the effects of alcohol and we all know the effects of being drunk can be bad, right?
Can be bad in terms of judgment motor coordination. Certainly driving drunk is a terrible thing. Get you or other people
killed and so on, but rarely do we hear about the change?
Has in neural circuits from just one or two nights of regular drinking again. Chronic drinking doesn't necessarily mean every day and every
night it could be the person that simply drinks every Thursday, or every
Friday or just once a week, has three or four drinks or maybe even a few more that person is going to experience a decrease in this top-down inhibition. So an increase in impulsivity and habitual
Behavior because the brake on those behaviors has been removed while they're drinking but also
changes in the very neural circuits.
That allow habitual impulsive behavior to occur more readily, even when they're not drinking.
And if you want to know the actual substrate for that, the seller substrate, I can briefly describe it. It's really interesting again, you don't need to know any biology to understand this. What it does is it increases the number of synapses the actual points of connection in the neural circuits that control habitual Behavior. So there's literally a growth of the neural circuits in your brain, that lead
to existing habit execution, right?
The performance of things. You already know how to
To do and a reduction in the neural circuits
or I should say a reduction in the number of synapses of the contacts,
within the neural circuits that are controlling Behavior. So this again is a not often discussed aspect of alcohol intake. Fortunately, it is reversible. So in animals or humans that undertake a period of abstinence of anywhere from two to six months. These neural circuits were returned to normal except in cases where
people have been chronically drinking, large volumes of alcohol for many, many years. And in
Most cases while there is some recovery of brain circuitry.
After people, get sober, meaning completely sober, they stopped drinking
entirely. There is evidence of long
lasting impact of heavy, alcohol usage throughout the lifespan, but of course, this doesn't mean that anyone that's suffering from alcoholism or that used to should not continue to focus on their health. You absolutely should
all is not lost. But for people who have been drinking for a lot of years, maybe you went to
college and you drank a lot
in those years and your neural circuits change if there's a period in which
You don't
drink alcohol again from two to six months and ideally
longer, those neural circuits can then be re modified
back to their original
state. So let's consider some of the other
neurochemical effects of alcohol on the brain and body. And
again, for right now, we're confining the conversation to people that are drinking on average one or two drinks per night. Now, some people might think that two drinks per
night is a lot, and a lot of that will depend on body weight. So for
instance, people who weigh 110 pounds,
For them to ingest, two alcoholic drinks is going to be substantially different in terms of the
biochemical effects. Then somebody who weighs 220 pounds of course, tolerance, will also factored into this genetic
background will also factored into this and indeed whether or not people have eaten will factor into this. So there are a lot of factors
and we'll talk about that for
the time. Being if you're curious about how food
impacts the effects of alcohol and your feelings of being drunk, you may
have heard for instance that if somebody's inebriated and
they want to sober up,
Should eat something turns out that does
not work. Here's how it does work. However,
if you eat something prior
to drinking alcohol, or while ingesting alcohol,
it will slow the
absorption of alcohol into the bloodstream. In other words, you won't feel as drunk as fast for many of you. This probably comes as no surprise
in particular if that meal includes carbohydrates fats and
proteins. Okay. The inclusion of all three, major macronutrients seems to slow the absorption of alcohol and
the bloodstream far more than any, than having any one of those or two of those macronutrients present.
Now, if you are already inebriated or
you've had a glass of wine or a beer and you eat something,
chances are that alcohol has already made it into your bloodstream because it moves into the bloodstream so quickly again, it's fat soluble and water soluble. So, within minutes, if you're on, if you have an empty stomach within 5 to 10 minutes, that
alcohol is going to be within your bloodstream and distributed throughout your body, maybe even faster.
Depending on the type of alcohol and your metabolism.
But if you're already drunk and you eat something, it's not going to sober you up more quickly, but it certainly will
blunt the effects of any additional alcohol that you might
consume. And if you're somebody who is concerned about
getting too drunk to Quick, even from a small amount of alcohol, having some food in your gut can certainly be beneficial
now, that's food and alcohol and the absorption of alcohol. But let's go back to talking about the biochemical and neurochemical
effects of
Hall on the
brain. We talked about top-down inhibition, and we talked about habitual and
impulsive behavior circuitry.
There are also dramatic changes in the activity of neurons that control the release of so called serotonin serotonin is a neuromodulator, it changes the activity of neural circuits and many neural circuits in particular. Those involved in mood and feelings of well-being. Recently, there's been a lot of interest in serotonin because of a study that was released that showed pretty conclusively, that serotonin levels can't really
Blaine, depression and depression like, symptoms. I want to make it very clear that, although that study did show that serotonin levels are not necessarily associated with depression. The study was interpreted by many to mean that SSRI, selective serotonin reuptake Inhibitors
which have the net effect of increasing serotonin. So these are things like Prozac
Etc. That those drugs are somehow
not helpful
because they increase serotonin and serotonin isn't involved in
Depression that logic doesn't really hold together. So I'm gonna use this as an opportunity to just clarify what really occurred there. And then
we'll talk about how serotonin relates to alcohol consumption in things, like feeling good. And in depression, the
key thing is this ssris can help alleviate
depression. That's right.
Ssris, can help alleviate depression. They are
often, not always associated with side effects dosages. Very important etcetera. But
they probably
Support relief from depression, by changing neural circuits, not necessarily by increasing serotonin self. That is increasing serotonin with these drugs. Likely change the neural circuits involved in mood allowing people to feel better through so called
neuroplasticity, which is the brain's ability to change itself in response to experience.
So there's a bit of confusion. And again I'm using this episode on
on alcohol to
highlight some of the confusion because I think it's timely because the study just came out and there's a lot of chatter about this out there that when people are
Depressed, it's not necessarily because serotonin levels are low. However, if serotonin levels are increased
with things like Prozac Zoloft and other ssris
often times there is yes a relief from depression but that's probably not because of restoring serotonin levels per se. It's probably because serotonin facilitates the changes in neural circuits that need to occur in order to for
people to feel elevated mood. Okay. So again that's a bit of a tangent and a sigh but I do think it's a vital one for people to know about again.
If you're thinking about taking ssris, you're currently taking them. And you've heard this news, definitely talk to your doctor. Again, there is great utility for some of these ssris and also in conditions like OCD. They've been shown to be very beneficial so we really don't want to throw ssris out as a potentially valuable treatment,
getting back to the effects of
alcohol on serotonin. It's very clear
Beyond any doubt that many of the circuits in the brain that are
involved in mood and
feelings of well-being and also its, or self image. And
And how we see
ourselves employ, the neuromodulator serotonin and alcohol. When we ingest it, and it's converted into acetyl, Alba hide, it goes. And that acetaldehyde acts as a toxin at the very synapses, the connections between the
serotonergic neurons, and lots of other
neurons. In other words, when we
ingest alcohol, the toxic effects of alcohol disrupt, those mood circuitry's
at first making them
hyperactive. That's right. Making them hyperactive is why people become
Really talkative people. Start to feel really good after a few sips of alcohol, these most people
do, and then as they can, just
more alcohol or as that alcohol, wears off serotonin levels and the activity of those circuits really starts to drop and that's why people feel less good and typically, what they do,
they go and get another drink and they attempt to got to restore that
feeling of well-being and mood. Now typically what happens is that as people ingest the third and fourth maybe even the fifth drink,
there's an absolute zero chance of
Them recovering that
energized mood, right?
Most people, as they drink, more and more will now start to feel more and more suppress. The forebrain is now shutting
down quite a lot. A lot of the
motor cortical areas that control coordinated movement and
deliberate movement start to shut down. So people start to slur their speech. People start to shuffle their feet,
people forget their posture, people start to lean on things, people start passing out on couches. There's a Great Depression, not depression of
the psychiatric depression sort.
But a depression of alertness and
arousal and eventually people will pass out.
Now I said most people because there's a subset of people that have Gene variants or who are chronic drinkers or who are chronic
Drinkers and have Gene variants
that as they
ingest the third and fourth and fifth drink, what happens? They
become more alert, they start talking more, they feel great, they have all sorts
of ideas about the fun. They could have that night and
they're the ones.
Is that if you've ever fallen asleep at a party for whatever reason or you getting tired and you're yawning looking around the room and
like these people are still drinking and partying in there.
Having what seems to be this amazing time often. Not always,
those are the future alcoholics in the room or those are the people that have a genetic predisposition for alcoholism.
Or those are The Chronic drinkers, the people who have built up enough of a tolerance or who have the chemical genetic make up, such that
increasing amounts of alcohol.
Make them feel better and better and better and of course, they too
have a threshold Beyond which their nervous system will start to get diminished and they'll
pass out and fall over Etc. But that threshold is way way higher than it is for most people. This is
important to understand and it's important to understand because I think everyone should know and recognize their own predisposition and kind of risk
in terms of developing alcoholism.
It's also important to understand because it relates
to the phenomenon of blackout.
Do you know many people think that blacking out is passing out? But blackout drunk is when people
drink and they're talking and doing things sometimes,
sadly, they'll or tragically, they'll often drive home or walk home or
they'll hop on a bicycle and ride home and they'll go swimming in the ocean.
All, of course, very dangerous activities to do. When people are really drunk or even a little bit Drunk In some cases, so these people will do these sorts of
things and they do them because they have the energy to do them and they feel good while doing them, but they are doing them. Well,
The activity of neurons in the hippocampus, which is involved in memory formation are completely shut off. And this is why the next day you tell them, hey, maybe
we should talk about what happened last night. What happened last night said, well, do you remember going the party? Yeah, it was great. We did this. We did this. And then what and it's very clear,
all of a sudden that they have no recollection of all the things that we're doing despite being awake.
Now, I wish I could tell you that there's some sort of blood tests or other
biomarker even a fingerprint test that would allow you to determine
ermine, whether or not you have a propensity to be one of these drinkers that has a predisposition for alcoholism. And if you've ever been blackout drunk, and certainly, if you've been blackout drunk more
than a few times, you should be
quite concerned. And as we talk more about the more chronic effects and long-lasting effects of alcohol consumption, little bit later in the episode. I think it will become clear as to why you should be
concerned but in any case there is something that can tell you whether or not you might
Be in that category versus likely not in that category. And I
alluded to this a couple of times already but I want to be really clear that when people drink no matter who you are, initially there's that shutting down of those, prefrontal cortical circuits. There's a gradual shutting down of the circuits that control memory but then people divided into these two bins and these two bins are the people who after more than a couple of drinks, start to feel sedated. And the people who
after more than a few drinks, do not start to feel sedated.
Now of course, there's going to be differences created by how quickly people are drinking, whether or not, they're
combining different types of alcohol, the types of alcohol Etc.
But in general that can predict whether or not you're somebody who has a predisposition
for alcoholism or not
one. Also very interesting finding is that alcohol changes the relationship between What's called the hypothalamus
and the pituitary gland and the adrenals.
Now, the hypothalamus is a small collection of neurons about the size of a large.
Gumball sits above the roof of your mouth and
houses neurons that are responsible for some
incredible aspects of our behavior, and our mindset things, like rage things, like sex drive, things like temperature regulation,
very primitive functions. Including
appetite thirst etcetera, alcohol because it
can go anywhere in the brain. Remember,
it's water and fat soluble has effects on the hypothalamus.
The hypothalamus normally provides
very specific signals to What's called the pituitary.
Gland. This is a gland that actually sticks out of the brain, but it
receives instructions from the
hypothalamus and then the
pituitary releases hormones into the bloodstream that go and talk to your adrenals. Your adrenal glands, sit right above your
kidneys, in your lower back, and the adrenals release as the name, suggests adrenaline, also called epinephrine and also
a molecule called cortisol, which
is involved in the kind of longer-term, stress response as some healthy effects to on the immune system, okay? So
the hypothalamic-pituitary-adrenal
axis
Axis. I know it's a mouthful. You don't need to remember the
names, but the hypothalamic-pituitary-adrenal axis, maintains, your physiological balance of what you perceive as
stressful, and what, you don't perceive as stressful,
people who drink regularly. So this again, could be
just one or two drinks per night, or it could be somebody that drinks just on Fridays or just on Saturdays or maybe just
on the weekend two to four drinks. Well, those people experience changes in their hypothalamic-pituitary-adrenal
axis
that result in
More cortisol, more of this so-called stress hormone being
released at Baseline, when they are not drinking, this is really important people who drink a bit. And when I say a bed, I don't mean one or two steps or even a glass of wine every once in a while. I mean, again people that are maybe
having one drink tonight with dinner and
maybe on the weekend, a few more. Can I offer a bunch of different patterns to explain how it could also be two or three drinks on Friday or six drinks only on Saturday?
All those groups experience increases in cortisol release from their adrenal,
glands, when they are not drinking and as a
consequence, they feel more stressed and more
anxiety when they aren't drinking.
This is a seldom talked about effective alcohol. Because so often we hear about the immediate
effects of alcohol and we've been talking about some of those effects effects, like reducing the amount of stress. I mean,
how many times have we heard? Somebody said, oh, I need a drink and then they have a
drink. Now, the
calm down. Now they've can shake off the thoughts about the day's work. They can start to think about things in a, maybe more grounded, or rational way.
Or at least they believe that or they can somehow just relax themselves. Well, while that very well, may be true
that it can relax them
when they are not drinking that level of cortisol,
that's released at Baseline, has increased substantially
again, this relates to define neural circuit between brain and body and it has to do with the ratio of cortisol to some of the
Other hormones involved in the stress response,
will provide a reference to the study that
describes how all of this works for those of you that really want to delve into it. But
let's go back to this issue of those who
are prone to alcoholism versus those who are
not. Remember there are
people who have genetic variants, that meaning genes that they inherited from their
parents. That make it more likely that they will become alcoholics. But there are also people who drink often, we start to experience this increase in alertness,
The longer, they drink across the night. Part of that effect, we think is because of changes in this hypothalamic-pituitary-adrenal axis. So alcohol is kind of a double
hit in this sense, it's
causing changes in our brain, circuitry in neurochemistry that at the
time in which we are inebriated are
detrimental and it's causing changes in neural circuitry that persist long past
the time in which we're experiencing the feeling of being tipsy or drunk. Now again I don't want to
demonize
I'm not saying, you know, if you have a glass of wine now and again or you drink a beer now and again, or even have,
you know, a
mixed drink now and again or a shot that that's necessarily terrible for you. I certainly do not
want that to be the message.
What I'm saying is that if people are ingesting alcohol chronically, even if it's not every night, there are
well-recognized changes in neural circuits there well-recognized changes in neural chemistry within the brain
and their
I'll recognize changes in the brain to body stress system that generally point in three directions increase stress when people are not drinking diminished mood and feelings of well-being when people are not drinking. And as you'll soon, learn changes in the neural circuitry that causes people to want to drink even more in order to get just back to baseline or the place that they were.
Are in terms of their stress modulation. And in terms of their feelings of mood
before they ever started drinking in the first place.
So again, I don't want to demonize alcohol, but I do want to emphasize that there are long-term plastic changes, meaning changes in neural, circuitry and hormone circuitry, that across a period of several months and certainly
across a period of years of the sorts of drinking patterns. I described which I
think for most people are going to sound like pretty typical, right? I mean, nothing that I described so
far was about drinking a case and I tour
We're about binging on alcohol in the way that we often hear about it in the news. These are pretty common patterns of alcohol consumption. I mean, all you have to do is
board a transatlantic flight
or actually go to an airport on a Sunday afternoon in a sunny area of the US. And, you know,
people are having three, four,
five, six beers,
Etc. Again, personal choice is personal choice. I'm not telling you what to do, but it's very clear that those
sorts of drinking patterns are changing neural, circuitry, and they're changing hormone circuitry. And I'd love to be able to tell you that they're changing them for the better but they
Simply are not they're actually changing them for the worse and worse is defined as making people less resilient to stress higher levels of Baseline stress and lower mood. Overall,
before we continue, with today's discussion,
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Now, I've been talking a little bit about genetic predisposition, but there are a couple of important points. I'd like to make about that. First of all, what sorts of
Genes are involved in setting someone down the path of alcoholism or not. Well, it should come as no
surprise. That the genes that chronic alcohol
usage.
Modifies. They tend to fall primarily in the pathways related to
genetic control over
serotonin receptors. Gaba receptors, remember that
top-down inhibition and the involvement of Gaba and no surprise the HPA the hypothalamic pituitary access. All of those
Of course, combined with environment that combined with patterns of abuse, right? We know that if you're in a social setting where a lot of people are drinking the likelihood that you're going to drink as much higher
Social pressures trauma, right? Some people will use alcohol
to self-medicate to try and turn off their thinking or to deal
with trauma Etc. So they combined with the environment, but the genes that are in the serotonin synthesis and receptor synthesis pathway Gaba and HPA axis combined with environmental
pressures,
Give rise to alcohol, use disorders. So there's a fairly coherent
picture that we have here, right? This is not a case where, for instance,
people that have a lot of the enzyme for metabolizing alcohol which we'll talk about in a minute, alcohol dehydrogenase. It's not like they are necessarily the people that become alcoholics. Whereas
certainly in certain cultures certain Asian cultures in particular, there are Gene differences that lead them to
have low levels of alcohol. Dehydrogenase they're actually people who have so little alcohol.
Ines that when they ingest alcohol, they get very red and they just feel sick. So if you're
somebody has a sip of alcohol and you just
feel horrible, it makes you feel nauseous. Chances, are you have
Gene variants? That create a
situation where you're not making very much alcohol. Dehydrogenase you would just simply can't metabolize alcohol. So, you just get a rapid buildup of the toxic effects of alcohol, the Seattle aldehyde. You're not converting it into those empty calories,
but in cultures where you have a lot of genetic variants and genes expressed in
people where they have.
A lot of
alcohol, dehydrogenase sure they can drink more and they're converting more of that
alcohol from its toxic form to a non-toxic form.
And yes of course you will observe more alcoholism in those Community because they're drinking more. But I do want to emphasize that the
environmental factors are playing a strong role there too, because if you can drink more, you're likely to
drink more. If you're somebody that feel sick
immediately from drinking, it's likely that you're not going to engage in alcohol consumption, especially if these things are genetically related and, of course jeans and culture and local
Acacia in the world tend to run together.
So,
Do you have the gene for alcoholism? Well there isn't one single Gene. Chances are if you have an immediate
relative who's a chronic abuser of alcohol or several relatives who are chronic abusers of alcohol well that's going to predispose you to be an alcoholic but since you don't know which genes you express unless you do genetic testing and those things are available but most people aren't doing that this assay if you will it's not an assay. As we say in a say is a test that you run in the lab to determine
In
something. And it's not one that I recommend that you go drink in order to
do, but if you've noticed that you or somebody else is somebody who can drink a lot throughout the night and have increased energy, you can just drink and drink a drink
and especially if there's blackout episodes. Not remembering things the next day, despite being alert throughout the entire night.
So on
well, then I would be very concerned that you might actually have a genetic variant predisposing, you to
alcoholism. The other thing that predisposes people to abuse of alcohol
is aged
people who start
Drinking at younger ages are greatly
predisposed to developing alcohol, dependence regardless of your family history of alcoholism. Okay, so I'm going to repeat that people
who start drinking younger are at Great risk for developing alcoholism, even if they
don't have alcoholism in their family. Now, of course, you don't have to be an epidemiologist, understand
that if you grow up in a family of Drinkers and alcohol is everywhere, and especially if there's
peer pressure or lack of
oversight, then there's going to be a high
Tendency or a higher probability, I should say that you will start drinking at a younger age, however,
even people that grow up nowhere near their relatives, if they start drinking at a young age. So, for instance at 13 or younger or 14, or 15, there's a much higher probability that they are going to
develop a long-lasting dependence on alcohol.
People who take their first sip of alcohol later,
15, 16 or one would hope even
later. I can say one would hope because I'm now that you know, age and generation where you, you know, you
think about all the things that young people do and you oh gosh if
they only would wait or if they only would abstain, you know. So what happens I don't know there's some neural circuit for that that I can't explain
yet but people who for instance drink only once they reach
legal age of drinking which in the u.s. I believe in every state is 21 years
old. If they take their first drink at 21 the probability that they'll go on to develop full-blown alcohol dependence, or
Call use disorder as it's called. AUD is very low. Now a subset of them will because they have such a strong genetic, predisposition,
or maybe life circumstances, create pattern in which they become a chronic drinker.
But I found this very interesting genes matter, but also the age in which somebody
starts drinking really matters. Now
whether or not that's because there are changes in neural circuitry as a consequence of that drinking
that make people want to seek out more and more alcohol
or whether or not there's some other
effect.
Maybe it's a change in hormones Etc that predisposes those young drinkers to become chronic drinkers or even full-blown alcoholic, certainly developing alcohol, use disorder, there's definition for that, we can talk about it, involves the amount of drinking over a certain period of time etcetera. So it's very
clear that drinking early in life creates a propensity for the development of
alcohol use disorder later in life.
And while there is a genetic component
to developing alcohol use disorder,
I find it very
Interesting that if people who have those Gene variants
delay, their onset of drinking,
well then the probability that they'll develop full-blown
alcohol, use disorder drops as well.
So again, it's genes and
environments, not an either/or and there's no single Gene for alcoholism.
Well, I promise you, I
will also talk about some of the documented, positive effects of alcohol.
Although they are very few and far between they do exist. But before I do that, I would be remiss if I didn't emphasize some more of the Terrible.
Bo things that
alcohol does in the way that it does it. And for those of you that enjoy alcohol. I again, I really like to say, I feel guilty about telling you this because I know how much some people enjoy a good drink every once in a while and I say good drink because some people do like the taste of alcohol. I suppose, I lucked out and then I don't really like the taste of alcohol and that just
puts me to sleep, but I know that people do enjoy it and I do want to point out that there is zero evidence that, you know, provided somebody
Of drinking age,
certainly not in the stage of brain development that having one drink or two drinks. Every now and again meaning every three or four weeks or
once a month that is
not going to cause major health concerns or major health issues for most people, I suppose, if you have zero or very little alcohol, dehydrogenase it might make you feel sick. But then you're not probably not the kind of person that's going to be drinking at all. So again, if you enjoy alcohol drinks, I'm not trying to
To take them away from you by any means.
But you should know what drinking does. If you're consuming
it in this kind of typical chronic pattern as we can now refer to it. Which is
that one or two a night, or
a few stacked up on Friday and maybe three or four on Saturday, this kind of pattern of drinking,
which is quite common. And one of the more serious effects that we should think about is the impact on the so-called
gut-brain Axis, or if it's a cup
of today's discussion at the gut
liver, brain axis
I
think the gut liver brain axis has ever been discussed on this podcast, maybe any podcast, although the moment I say that, I'm gonna, you know, the gut liver, brain, axis people are going to come after me with. I suppose, gut liver brain and
brains in any event,
you have a brain
you have a gut that got runs from your throat down to
The end of your intestine,
your gut and your brain communicate by way
of nerve cells, neurons, and nerve connections. The vagus nerve in particular and by way of chemical signaling
your gut also communicates by way of chemical signaling and believe it or not, by way of neural signaling to to your liver. And as we talked about earlier, the liver is the first site in
which alcohol is broken down and metabolized into its component parts.
The liver is also communicating with the brain through chemical signaling
and neural signaling. So we have the gut liver, brain
axis and what you find is that people who ingest
alcohol at any amount
are inducing A disruption in the
so-called gut microbiome, the trillions of little micro bacteria that take resident in your gut and that live inside you all the time and that helps support your immune system and that literally signal
Wave electrical signals and chemical signals to your brain, to increase the release of things like serotonin and dopamine and regulate your mood generally in positive ways. Well alcohol really disrupts those bacteria. This should come as no surprise. I mean earlier, we talked about this and it's well known. If you want to, you know, it's sterilized. Something you might kill the bacteria, you pour alcohol on it and I can remember scraping my myself or cutting myself. I was always the injuring myself when I was a kid and you know the moment they take out the peroxide. You like oh boy, here it comes. But if there's no
I'd around
and you got a wound there and need to clean it
out. Yeah. They'll use alcohol which I
do not recommend, by the way. And that's one of the
harshest ways to clean a wound. But
for centuries, thousands of years really,
alcohol's has been used in order to clean things and kill
bacteria. So, alcohol, kills bacteria and it is indiscriminate with respect to which bacteria it kills. So when we ingest alcohol and goes into our gut, it kills a lot of the healthy gut microbiota. At the same time, the metabolism of alcohol
and
Liver which You. Now understand that pathway involving NAD, acetyl-coa aldehyde and
acetate. That pathway is pro-inflammatory. So it's increasing the release of inflammatory cytokines things like il-6, Etc, tumor necrosis
Factor Alpha if you'd like to learn more about the immune system, we did an episode all about the immune system you can find it, you Vermin lab.com and teach you all the basics of what our cytokines what our mast cells, Etc.
In any event, all these pro-inflammatory molecules
owls, those are being released. You've now got disruption of the gut microbiota. As a consequence, the lining of the gut is disrupted and you develop at least transiently leaky gut that is bacteria, that exist in the gut
which are bad bacteria. Can now pass out of the gut into the bloodstream so you've got a two-hit kind of model here in biology. We talked about to hit models. That is kind
of a one plus one equals four and it's generally when you hear to hit it's not a good thing.
So you got bad bacteria from partially broken down
food, moving out of the gut, the good bacteria in the gut have been killed. You might say, why isn't the alcohol kill the bad bacteria in the gut? Well,
the bad bacteria that are from partially digested food, oftentimes escape the gut
before the alcohol can disrupt them. And so now you've got leaks in the gut wall. You got the release of this bad bacteria. You've got
inflammatory cytokines and other things being released from the
the liver and they are able to get into the brain through neural. What's called a neuro, immune signaling and what's really bizarre in terms of the way
that this manifests in the brain. I mean, it's not the
way I would have
done it. But then again, as I always say, I wasn't consulted at the design phase and anyone who says they did, you should be very skeptical of
them.
The net effect of this is actually to disrupt the neural circuits that control regulation of
alcohol intake and the net effect of that is increased alcohol consumption. So this is just
terrible, right? I mean to your take in something that disrupts to systems the
gut microbiota and it disrupts in two ways, it's killing the good gut microbiota and
it's allowing the bad bacteria to move from the gut into the bloodstream. You've also got pro-inflammatory cytokines coming.
The
liver and those converge or arrive in the brain and create a system in which the neural circuits cause more drinking, that's a bad situation. And this is why people who drink regularly, even if it's not a ton of alcohol,
again, of this sorts of patterns are drink out, talked about before. And
certainly for those that are
chronic heavy drinkers,
what you end up with is a situation in which, you have inflammation in multiple places in the brain and body and the desire to drink
even more
Or, and to further exacerbate that inflammation in the gut leaky nests. So this is basically a terrible
scenario for the gut liver, brain axis, and it's especially prevalent in
so-called alcohol. Use disorder again. People they're ingesting somewhere between 12 and 24 drinks per
week. For those of you that are interested in learning more about the gut, liver brain axis
and in particular alcohol. Use disorder I'll provide a link in the show notes captions, there's a wonderful review on this the details that
but on the positive side it points to the possibility that at least some
Then, at least some of the negative
effects of alcohol consumption. Whether or not you're somebody who's
currently ingesting alcohol or
who used to ingest alcohol in this, trying to so-called repair these systems of the brain and
body whether or not replenishing. The gut microbiota is going to be beneficial and we know that there are ways to do that and we know that there's at least some promise for the
ability for this system to repair itself. How
does one do that I've talked before about this on the podcast? But studies done by colleagues of mine
at Stanford just in Sonnenberg who's been on this podcast as a guest.
An amazing episode all about the gut
microbiome and his collaborator. Chris Garner also at Stanford School of Medicine, have explored not alcoholism. But what are ways to improve the gut microbiota and particular to reduce the
production of inflammatory, cytokines. And to adjust, What's called the inflammatory, you've heard of The genome and the proteome ETC. Well, the inflammatory is the
total array or at least the near total array
of genes and proteins that
Control
inflammation. How can you reduce inflammation and make that inflammatory? Um, healthier. Well, they've shown that two to four servings of fermented foods
per day. And here, I'm not referring to fermented alcohol and talk about low sugar. Fermented food. So things like kimchi, sauerkraut. Natto for the, for those of you that like Japanese food, there are others. I know things like
kefir, things like yogurts have a lot of active bacteria. Again, low-sugar varieties of all these things, those are terrific.
Vic at reducing inflammatory markers and at improving the gut microbiome one could imagine that either inoculating oneself
from some of the effects of alcohol. Although I'd prefer that people just not drink, alcohol chronically
frankly or if somebody's trying to repair their gut microbiome because they ingested
a lot of alcohol or because they had a lot of these inflammatory cytokines for many years or even a short period of Time. Regular ingestion of two to four servings of these. Fermented foods can be quite beneficial
We'll make it clear that is not been examined specifically in the context of alcohol, use disorder. But because
a huge component of the negative effects of alcohol use
disorder are based in this gut liver, brain axis and disruption in the gut microbiome in the inflammatory. Cytokines it stands to reason that things that are well established to improve.
Inflammation. Status. In other words, reduce inflammation such as ingesting two to four servings of low sugar. Fermented foods per day,
Make sense in terms of trying to repair a replenish, the system, one could also Imagine taking probiotics or prebiotics, certainly that would work as well. Although I've sort of favored the discussion around fermented foods and replenishment of the gut microbiome mostly because there are more
studies that have examined that in humans. And
because of the direct relationship, that's been established between doing that and reducing - markers, within the inflammatory, and I should mention
along the lines of repair and Recovery. I put out a question on Twitter the other day.
I
said, what do you want to know about alcohol? I got more than a thousand questions and we'll take some more of those questions, a little later in the
episode, but one of the things I noticed is that many of the questions hundreds. In fact, related to the question of. Well, if I drank a
lot previously, am I doomed? Can I reverse the negative effects? Or, you know, I'm trying to drink less and I'm trying to improve my health, as I, as I do that, what should I do? Well,
certainly focusing a
bit on the gut microbiome ought to be useful.
The other thing I should mention is
As people wean themselves off alcohol, even if they're not full-blown alcoholics or have alcohol use disorder. They should understand that that increase in cortisol that we talked about earlier that leads to lower stress threshold and
greater feelings of anxiety and
stress.
That's going to be present and it's going to take some time to dissipate. So for some people it might even just be helpful to realize that as you try and wean yourself off
alcohol or maybe even go cold turkey that
increased anxiety and feelings of stress should be expected. And in that case, I would point you to an episode that we did
on Master stress, you can find that again at huberman labs.com. It's got a ton of Behavioral nutritional supplementation. Based exercise based, I suppose exercises
behavioral, but a lot of tools you can navigate to
Those easily because we have time stamps, you can go right to the topic of
Interest. Those tools are going to be very useful
in trying to clamp or control your stress.
And the point here is just that some increase in
stress should be expected and it should be expected because of that increase in cortisol that occurs with even low level consumption yet, chronic alcohol consumption.
Now, I'd like to talk about a fairly common phenomenon, which is
post alcohol. Consumption malays also referred to as hangover
hangover is
Is a constellation of
effects, ranging
from headache, to nausea to.
What's sometimes called anxiety, which is anxiety that follows a day of drinking
anxiety. I think we can understand physiologically. If
we think about that process of alcohol intake, increasing the amount of cortisol and the ratio of cortisol to some other stress
hormones that well explains,
why some people wake up the day after or even the day.
The day after
a night drinking and feel anxious and not
well and stressed for reasons. They don't understand. So
if you're somebody who
experiences hang a xiety then again I refer you to the master stress
episode that we put out some time
ago. And you can find that huberman lab.com tools to deal with anxiety tools to deal with stress. Ranging, again from behavioral to nutritional supplement, based etcetera,
that of course, is not
justification for going out and drinking so much that you get
Get anxiety,
induced hangover. But for those of you that are experiencing post,
alcohol, consumption anxiety, as it were, that could be a useful resource because I certainly don't want anyone experiencing uncomfortable amounts of anxiety, and there are great tools and resources for that. Now, the other aspects of
Hangover such as the stomach ache or headache or feelings of malaise or fogginess, those can be related to a number of different things and probably are
related to a number of different things.
First of all, the sleep that one gets
after even just one. Yes, even just one glass of wine or a beer is not the same sleep that you get when you don't have alcohol circulating in your system and not trying to be a downer here.
But this was discussed in the human Lab podcast episode
where I had dr. Matthew Walker from UC Berkeley on and, of course, dr. Walker is a world expert in sleep runs, one of the preeminent laboratory studying sleep and its effects wrote The Incredible Book. Why
we
Sleep and so on dr. Walker told me and it certainly is supported by
lots and lots of quality peer reviewed studies in animals and in humans that when alcohol is present in the brain and bloodstream that the architecture of sleep is disrupted,
slow-wave sleep, deep sleep
and rapid eye movement, sleep. All of which are essential for getting restorative night sleeper, all
disrupted. So, for those of you that are drinking a glass or two of wine or having a hard liquor drink or a beer in order to fall,
If the sleep you're getting is simply
not high quality sleep or certainly not as high quality as the sleep you be getting. If you did not have alcohol in your system,
of course, when we're talking about hangover, we're talking generally about the consumption
of more than just one or two drinks. Of course, for some people, one or two drinks is probably sufficient to induce
hangover, but for most people, it's going to be having three or four exceeding. That's their
typical limit as it's called again, not the legal limit, that's a whole other business
but when one ingest, too much alcohol for them,
One of the reasons they feel terrible,
the next day is because their sleep isn't really good sleep. In fact, it's not even sleep. It's often considered pseudo. Sleeper least. That's what it's called in the Sleep science field because people are in
kind of a low-level hypnotic kind
of trance. It's not real sleep there, multiple ballots of waking up, they may not even realize they're waking up multiple times.
Okay, so there's the sleep-inducing effects, then there are the disrupted gut microbiome
affect some of which we talked about earlier. So, now, you understand the mechanism,
Of alcohol destroying
good healthy gut microbiota, which then leads to leaky gut and things of that sort. But one could imagine, again, could imagine. And there is some evidence starting to support this. That again, ingesting low-sugar fermented foods or maybe in
Prebiotic or probiotics to support the gut
microbiome, might assist in some of the gut
related malaise associated with hangover other words, get those gut microbiota healthy again, as quickly as possible, or maybe even
Before you drink, have those gut microbiota healthy, I
would hope that you do that. I think everybody should be doing something to
support their gut microbiome whether or not the ingestion of low sugar fermented foods daily, or at least on a regular basis or ingestion of probiotic or Prebiotic. The gut microbiome is so important for so many different things in terms of hangover
and headache. We know that
that's caused by vasoconstriction, the constriction of blood vessels that tends to occur as a rebound after a night of drinking, alcohol can act as a vasodilator, it can do.
Like the blood vessels part of that is associated with the
increase in so-called
parasympathetic tone. We have an autonomic nervous system. It's got a sympathetic component. These are neurons that make
us more alert and if they're very active, they make us very stress. There's also the parasympathetic aspect of the autonomic nervous system. This is all just fancy geek speak for the parts of your brain and body. The nerve cells that make you very relaxed when you're very relaxed, there tends to be vasodilation. It allows for
more movement of blood.
And other things through the bloodstream and alcohol
tends to induce some vasodilation at least in some of the capillary beds and then when the alcohol wears off, there's vasoconstriction and people get brutal headaches.
That's why some people will take aspirin or Tylenol
or Advil or things like that, that sort of non-steroidal anti-inflammatories, I should mention,
there's a lot of literature coming out that some of these
non-steroidal anti-inflammatory, drugs are not good for us for a number of different reasons and way they
Deliver the way they impact the
immune system and no surprise
the way they impact the gut microbiome. So I'm not one to tell
you what medications to take or not take but you certainly would want to do a
quick web search of effects of non-steroidal anti-inflammatories and aspirin before you start taking those or stop taking those for that matter. Generally, they will alleviate headache but they can often have other issues including liver issues, and keep in mind, the night after drinking your liver is
He taken a beating because of the need of the liver to convert alcohol from acetaldehyde into a state, which is now a pathway that you will understand. So I'm not certain and in fact, I believe it's not the greatest idea to burden your liver further through the use of things that are going to cause it to have to work harder and metabolize things. If the goal is simply to alleviate a headache,
there's a lot of kind of lower old school or about how to relieve a hangover. We already talked about how
eating food won't
Do that but eating food will
prevent the rapid absorption of even more alcohol into the bloodstream. There's the lure that one should simply ingest more alcohol. What? Terrible advice that is that's just going to delay an even worse. Hangover? However, I'd
be remiss if I didn't say that. The reason that that
myth came to be or that I should say. That truth came to be because indeed ingesting more alcohol will alleviate a hangover. But then a worse. Hangover will show up
the
That came to be is because ingestion more alcohol will cause
those constricted vessels that are giving the headache to dilate again. But of course, ingesting more alcohol to relieve a hangover, simply a bad idea. Just don't do it. I think this is called the hair of the dog approach. Maybe someone can put in the show, no captions on YouTube. Why it's called the hair of the dog can come up with a few ideas but they're not going to be very good ones and some of them would probably even be outright ridiculous.
So do not ingest, more
alcohol. Simply to try and
Recover from a hangover. I know many people have tried that one before, but that's a terrible idea.
Now, one thing that you'll also hear out there is that deliberate cold exposure, for instance, taking a cold
shower, might relieve
hangover. I find this one particularly interesting because we've done episodes on the benefits of deliberate cold exposure. We have an
entire episode about that. You can find it again Hyrum. Lab.com, their direct links to some of the tools related to deliberate cold exposure and we have an entire newsletter on deliberate cold exposure, protocols. You can find
On huberman lab Commodore, neural network newsletter. These those of you that are interested in ice bath and cold showers and ways to leverage those, you can find that their
what you won't find. There is a description of how to use deliberate called exposure for sake of
treating hangover. But here,
I went into the literature and I found something kind of interesting. There is some evidence that increasing levels of epinephrine in the bloodstream can actually help with alcohol clearance. That was very surprising to me and I want to point out this is not a large and robust literature but there's some evidence pointing to the fact that
And levels of epinephrine adrenaline are raised in the brain and blood stream. That some of the components of alcohol metabolism can be accelerated and some of the inebriating effects of alcohol can be reduced. So maybe this old school lure of taking a cold shower actually has something to it. So in thinking about the use of
deliberate cold exposure, in order to reduce the effects of hangover or two more
rapidly clear,
alcohol from the brain. And bloodstream, I want to be
very clear and I want to emphasize your safety.
The way to do that is to understand that alcohol lowers
core body temperature. Okay. It can make people slightly hypothermia kits going to drop core body temperature.
So if you were inebriated and you went and got into a body of water, right, a pool, or a lake or something, first of all, that's extremely dangerous to do. While you're inebriated
people drown all the time, people drown, they die as a consequence of doing that so please don't do that.
But also if it's very cold water, your core
body temperature is going to drop.
Not even further. Now, if you've heard the episodes that I've done on deliberate cold exposure
previously, I've talked about how
normally when people are not ingesting alcohol, they get into an ice bath or a cold shower and their body temperature, initially dips, but then it
rebounds and increases, that's a process that's going to occur.
When people do not have alcohol in their system,
when you have alcohol in your system, one of the reasons that you become hypothermic is because there's a disruption in those hypothalamic brain areas in particular, the brain area called the medial preoptic area that regulates
core body temperature. So it's not so much that
alcohol makes you cold. It's that alcohol
disrupts, the Central Command centers of the brain that control temperature
regulation, and that leads you to be
slightly hypothermic. So if you then go get into a very cold lake or you get into even a cold shower or an ice bath, there's the possibility of you going. Very, very far down the ladder into
very hypothermic territory and that can be very dangerous.
Now in terms of dealing with hangover when the alcohol has been largely cleared from
Our system. Well, that's where some of this old lure combines with some of the modern science and says, well, if you can Spike, adrenaline, and certainly getting into an ice bath or getting into a cold shower, or any kind of cold body of water provided,
you can do that safely, that will sharply increase your adrenaline. And I should say your dopamine, that's been shown. And we've talked about this on the podcast before you get these
long extended
increases several hours of increases in dopamine from deliberate, cold exposure. It's well documented in humans, by the
way,
So one could imagine using deliberate called exposure as a way to accelerate the recovery from Hangover provided. That's done safely. I think
there's no reason to not explore that and if you wonder
what safely is and what temperature is to use, please check
out the episode on deliberate cold exposure,
cold showers. Therefore might actually be one way to at least, partially relieve hangover. Certainly, the science from various places in the literature converged to say that, but again, be careful please.
Please, please be careful not to get into
cold water when you are, inebriated. It's absolutely dangerous for all the obvious reasons and it's
dangerous. Also, for the non obvious reasons,
not the least of which is the dramatic decreases in core body. Temperature that can make you dangerously hypothermic. Now, how would you go
about using deliberate cold exposure to accelerate recovery from Hangover? Well, there. I would look to the kind of standard Protocols of, you know, one, two, three minutes or maybe even six minutes if you can tolerate, or if you're really cold adapted, if you
do seven or
ten minutes in a cold shower, although, that could be a lot. Most people are going to
experience a sharp increase in epinephrine, adrenaline, and a long-lasting increase in dopamine from 1 to 3 minutes of deliberate
cold exposure. Ideally done immersion up, to the neck again. Do this safely, please, please please, or a cold shower where you're getting under the shower, as much
as possible. How cold? Well, that's going to vary person to person. I suggest making it as cold as uncomfortable. Such that, you really
want to get out. But, you know, you can stay in safely. Without for instance, give yourself a heart attack because if
Or is it really, really cold? Of course, you give yourself a heart attack, most showers won't go that cold, although probably some will, again please use caution spike, your adrenaline spike, your dopamine, with deliberate cold, exposure, safely,
other components of
Hangover that could be good targets for trying to alleviate hangover. And here, I hope you are getting the picture because it is accurate to say that hangover is a multi-faceted phenomenon. It's not like one molecule in one receptor. It's a bunch of things happening in the brain and
body, but is the dehydration associated
with
Alcohol, alcohol is a diuretic for multiple reasons. It causes people to excrete not only water but also sodium sodium, is an electrolyte critical for the function
of neurons, so making sure that you have enough sodium potassium and magnesium
so called electrolytes is going to be important for proper brain function bodily organ function.
Even for people who have just had one or two drinks a night before, it's likely that your electrolyte balance
and your fluid balance is going to be disrupted. That's because alcohol also,
Drops the so called vasopressin pathway. I talked a lot about
vasopressin and the way that
it interacts with and controls different aspects of water, retention and water released from the body in the form of urine in the episode on salt. So you again, I'm referring to huberman live.com as the site where you can find that episode on salt balance and ways to restore electrolyte
balance. Having your electrolytes at the proper levels, before you drink is ideal, some people will say for every glass of
alcohol
That you drink, you should drink one glass of water. I would say better would be two glasses of water, given the dehydrating effects of alcohol, and even better would be water with electrolytes. That certainly would set you up for a better day the next day.
And if you don't manage to do that, because I suppose it's
kind of geeky walking around with electrolyte packets out at the bar or whatnot. Although, you know, Kiki, my book is a good thing.
The next day, you could take
some electrolytes upon waking, maybe even some before you go to sleep.
The night of drinking,
so hangovers made worse by Disturbed, sleep made worse by disrupted. Got my bio made worse by disrupted, electrolytes, made worse by the depletion of epinephrine and dopamine,
that's why replenishing, the microbiome with fermented foods. Low sugar fermented foods that is that's why using safe deliberate cold exposure for spiking adrenaline and for
increasing dopamine
and that's why consuming electrolytes are all going to be beneficial.
The folks over at examined.com a website that I really
like because it just has so much useful
information have assembled a list of things that have been proposed purported to
improve, or I should say to remove
the effects of hangover. And as they point out and I would like to point out over there, there isn't a lot of quality science to support the idea that
anyone compound can eliminate hangover, that's
probably because hangover again, arises from
Organs and tissues and systems in both the brain and
body. Nonetheless, they have a terrific list over there of things. Everything from Japanese pear. Fruit juice has been proposed to do this, to some other really esoteric. Things even things like yohimbine, frankly, when I look at the literature there and Elsewhere, One simply cannot find
the magic substance, the one herb, the one potion that can wipe away
hangover.
In rid of
Hangover is going to be best solved by doing a collection of a small number of very powerful things of which I've already listed off, a few.
However, there are some additional things that one can do for relieving hangover. And one of them is to be very thoughtful about what sorts of alcohol, one consumes. So I find this interesting there have actually been studies of
Which types of alcohol lead to the
greatest hangovers. There's actually a lot of Legend and lore about this as well.
Some people have said, for instance, that drinks that have a high sugar
content lead to Greater hangovers
turns out, that's not the case, at least, that's not what the science points to. If you look at the expected hangover severity, what you find is that at the bottom end of the scale, there's a drink that I'm not going to tell you for the moment, but what you find is that near it is, for instance, be
The consumption of beer provided it is not overconsumption, right? It's
not far, beyond the tolerance of the individual says, one or two beers
is less likely to cause a hangover, than
say, Whiskey and a glass of whiskey. Or I should not as much whiskey as
beer, of course. But glass of whiskey, for instance, is more likely to cause hangover than gin,
is it turns out, again, this is
what's falling out of the data and yet a glass of
Rum, or red wine is more likely to cause a hangover than any of the other things. I've mentioned so far at the top top, top of the list of drinks. That induce hangover is Brandy and one could then say, well, doesn't Brandi have a lot of sugar. Maybe it's the sugar that's causing hangovers and this is something that's been again discussed over. And over that people say, oh it's the high sugar drinks, that cause
hangover, it turns out, however, that
when one looks at drinks, alcoholic drinks and sugar content and hangover at the very bottom of the list.
Is
gosh, this makes me cringe just to think
about is ethanol diluted in orange
juice. I can't believe people actually drink this,
but ethanol diluted in orange juice. So this is not vodka and orange juice. Okay, vodka was third on the list from the bottom
of drinks. That induce hang over
again. This is within amounts that
are comfortable for the person to drink that they have enough experience with, or that they have the body weight to tolerate without getting very, very drunk.
So the point is that, if it were sugar,
It's causing hangover. Well, then the ethanol and dilute in orange juice
would probably be at the top of the list into in terms of inducing hangover, but it's not, it's at the bottom of the list and Brandi is at the top of the list.
So what you find is that what scales from ethanol,
diluted orange juice to beard a vodka to Chan here, I'm a sending the hierarchy of things that cause hangover gin white wine, whiskey rum, Red Wine and then Brandy at the peak, it sort of the world heavyweight champion of Hangover inducing
drinks.
Well, what's increasing our congeners within those drinks, congeners are things like nitrides and other substances that give
alcohol, its
distinctive flavor and that also lead to some of the
inebriating effects of alcohol.
Now then you ask? Okay well what is it that these congeners are doing and what are these nitrates
doing and guess what, while they do have effects on the brain and on other tissues, their main effects are to disrupt
Up the gut microbiome. So what
this points to again, is that having a healthy
gut microbiome, and perhaps, ensuring that you bolster your gut microbiome,
the day after drinking is going to be, especially
important for warding off hangover or at least reducing the effects of hangover or the symptoms of hangover or
both. I would love to see a study on this.
I could imagine designing the study myself, although this isn't really the sorts of things. My laboratory does.
But you can imagine some people getting probiotics and prebiotics um regularly some just after drinking or low sugar
fermented foods and see what the effects are in terms of subjective
effects of Hangover. But also some physiological measures.
I think the way to think about hangover overall is that again, it represents a multi-faceted multi-organ multi tissue phenomenon. And the best way to deal with it
is as a multi-cell multi tissue multi.
Cool phenomenon
and before I list it off, some of the things that one could do in order to adjust hang over again. The one that comes out at the top of that list I
believe least, based on my read of the data is to support the gut microbiome, and
certainly not to ingest
more alcohol. And I suppose, if we were to get really honest with one another and ask, what's the
best way to avoid a
hangover? It would be to not drink in the first place.
So we've covered the major effects of
alcohol that
To this state that we call drunkenness or inebriation. Again, there's a range there, you can be tipsy, people can be blackout, drunk, people can be passed out drunk. We've also talked about hangover and the fact that it's a multi-faceted phenomenon and recovery from Hangover involves a multi-faceted approach.
Next, I want to talk about tolerance tolerance to alcohol is a very interesting
phenomenon, it has roots mainly in the brain and in brain
systems.
There's not time in the world, let alone within this podcast to get into all the
aspects of Tolerance, there are more than 10 different
types of Tolerance. There's functional tolerance, chronic tolerance rapid tolerance. There's
metabolic tolerance, there's psychological tolerance, let's
keep it simple for sake of today's discussion. And for those of you that are interested in learning about all the different types of Tolerance and aspects of Tolerance, there's an excellent review. We will provide a link to this. This was published in 2021 so it's pretty recent in the
journal pharmacology.
And behavior. Incidentally are not twins only. That was the first Journal I ever published in. So I have a
particular affection for that journal. Nonetheless, it is called tolerance to alcohol a critical yet, understudy factor in alcohol addiction. And while this paper does include alcohol addiction in the
title, it's not just about alcohol addiction.
Here's the basic summary of what tolerance is. First of all tolerance, refers to the reduced
effects of alcohol with
Repeated exposure
and it is caused mainly By changes in neurotransmitter systems in the brain that are the direct consequence of the toxicity
of alcohol that aldehyde molecule that we talked about before.
There's an enormous number of chemicals that change with repeated exposure, to Seattle aldehyde, everything from Gaba to dopamine and serotonin second messenger systems adenosine and on and on rather than go into each of those in detail. I just want to talk about the Contour.
Of the reinforcing and the tolerance
inducing effects of alcohol. What do I mean by that? Well,
here we are back to our old friend, meaning the molecule that comes up over and over again,
in these podcast episodes, which is dopamine
whether or not, somebody has a
predisposition alcoholism or not, whether or not they're experienced Drinker or
not. When people initially start drinking, there are
increases in dopamine or what we call dopaminergic, transmission, dopamine is involved in
motivation, craving it creates
a sense of well-being and increases energy again, typically only at the beginning of alcohol exposure that occurs in most people as a sharp Spike as they increase again, if somebody does not have
alcohol dehydrogenase or has very low levels of the enzyme that convert that acetaldehyde into acetate,
And metabolize alcohol. In other words, they will feel sick and lousy
in a way that will override any
recognition of the dopamine release their guns. Be the people that are listening to this and just thing alcohol. Just makes me feel sick. I don't like it. Okay, that's a specific sub category of
people, but most people experience, some sort of mild Euphoria. That's why so many people drink. Right? At the current estimates are
that in most countries and certainly in the US as many as 80% of the adult legal drinking age, population, drinks, alcohol, and that number could be
Be even higher now because in the last couple of years has been a trend towards increased alcohol consumption, especially in the wake of the pandemic and during the pandemic topic for another time.
So there's an increase in dopamine and an increase in serotonin. So it's kind of an increase in well-being, an increase in mood, but it's a very short-lived increase very soon after and actually triggered by that increase is a long and slow reduction in dopamine and
serotonin and related molecules in
circuit.
so basically what you're getting is a blip of feel-good followed by a
long slow Arc of feeling not so great, which is why typically people will drink again and again across the
night
The key thing to understand about tolerance is that with tolerance the duration of that long slow reduction in dopamine and serotonin gets even longer. In other words, the negative
effects of alcohol that happened after the initial feeling good
extend longer. And in fact get more robust. However, there's also a reduction
in the reinforcing properties of alkyl. There's a
shrinking of the
Feel-good blip that happens when one first ingest alcohol and this
has been measured in animals and humans. So the first drink that somebody has provided, they have enough alcohol.
Dehydrogenase that doesn't make them feel nauseous and sick right away,
they feel really good and then as it wears off, they feel kind of lousy.
And they want to drink more. So they might drink more
with each subsequent, drink, and even drinks on different nights or even different weeks, the amount of dopamine that's released is
reduce the amount of Serotonin and that's released is
Deuce. So what you're
getting is less and less of the reinforcing
properties of alcohol, the feel-good stuff and
more, and more of the punishment pain. Signal aspects of alcohol. This is the Contour of chemical release in the brain. That was referred to
by my colleague. The incredible dr. Anna Lemke, who is a medical doctor? She wrote The Incredible Book dopamine Nation. She was a guest on this podcast. I'm Joe Rogan podcast on Rich rolls podcast and several other podcast
World expert in a dictionary.
She talked about this pleasure pain, balance that extends Beyond alcohol to things like sex, and gambling and two. Other behaviors that can potentially become addictive but certainly includes alcohol.
So tolerance, it seems is a process in which people are ingesting more and more
alcohol as an attempt to get that
feeling of well-being back. But what they're really getting is an extended period of punishment of
pain and of malaise from the
alcohol. Now
You might say, well, how does that relate to tolerance? What, turns out what they do behaviorally, and when I say they, I mean animals, do this, in humans, do this is, they start drinking more and more in an attempt to
activate those dopamine and serotonin neurons and receptors.
And as they do that, there is an increase in
alcohol dehydrogenase. So the enzyme that metabolizes alcohol is increased because the body and liver have to contend with all that alcohol.
So now you've got again, the to hit model, you're getting less of the feel-good
chemicals.
More of the - chemical release or pattern of subjective. Feeling I should say and
your metabolizing alcohol, more quickly and more readily. But it's not taking
you to a better place in terms of how you feel. That's one of the major underlying reasons for what we call
tolerance. So if you're somebody who drinks and you notice that, the feeling that you are
seeking with alcohol
is now requiring an additional drink or drinks, plural chances are, you are
disrupting the
Dopamine and serotonin, urging systems of your
brain and you are doing that in a way that is increasing the pain and Punishment signals that
follow alcohol ingestion. And again, that's not just on the night that you're drinking but afterwards as well, is that all
bad news? Well, pretty much, but, the good news is that if you abstain from drinking for some period of
time, then of course, these systems reset,
how long you need to abstain,
will depend on how much you were drinking and how long you were drinking. For
certainly people who have our alcohol use disorder.
Who are alcoholics their main goal should be to
quit alcohol, completely. I know there's some debate about this and I don't want to get into that debate because I'm certainly not going to try and direct anyone's recovery their expert counselors and an MDS and people can work with people. In fact for some very heavy Drinkers
and people with serious alcohol use
disorder going cold turkey that is stopping drinking completely can actually be medically dangerous. So the path to sobriety for certain people looks different than the path to sobriety for
other people. What I'm referring to
Here are people that are ingesting again somewhere between on average one to two
drinks per night, whether or not that's done night tonight, or whether or not that's condensed to weekend. Use,
I know a number of people are going to
ask, perhaps, our
screaming is drinking. Good for me in any way. For instance, many people have probably heard that Resveratrol is good for people. In that red wine is enriched and
Resveratrol hate to break it to you, but the reality is that
if indeed Resveratrol is good for us and there's some debate about
this
People say strongly yes some people say no other people say maybe the amount
of red wine that one would
have to drink in order to get enough. Rest of are troll in order for it to be health-promoting
is so outrageously high. That it would surely
induce other negative effects that would offset the positive effects of Resveratrol. So I
wish I could tell you different. Again, I'm
not here to be the bearer of bad news,
but the statement I just made was
confirmed by dr.
David Sinclair. When he was a guest on this
podcast, it's confirmed by other.
Researchers who work on Resveratrol and related Pathways? I wish I could tell you that red wine is good for your health and indeed it might be
through some other mechanisms. So for instance, there have been studies of low to moderate red wine consumption. This would be anywhere from one to four glasses per week and I don't mean enormous
classes. I mean, six ounce
glasses of red wine. And those cases some of the stress reduction that can be induced by consumption of red.
Mine. Maybe some of the other micronutrients and components
within red wines, in particular, red wines that come from particular grapes and this gets really nuanced and frankly is not well worked out in the peer-reviewed literature. Certainly not clinical trials. At least not that. I'm aware of tell me. If you're aware of a great clinical trial on this, well, there may
be some positive effects of that very low
level of consumption. I'm not trying to take away anybody's red wine. I'm not trying to
take away anybody's anything I
Would be remiss. However,
if I didn't tell you that
Resveratrol, as the
argument for drinking and drinking red wine in particular, is just not a good one, it's just not supported by the peer-reviewed research, a
few other things
about alcohol and health, the beginning of the episode, I referenced a study showing that indeed not just heavy alcohol consumption of 12 to 24 more drinks per week, but also light to moderate alcohol. Consumption of any type wine beer.
Etcetera, does reduce the thickness of the brain. It really does reduce cortical thickness. In fact, it actually scales with the amount of alcohol that people drink and
this has been well documented in a number of different studies, that can provide a link to several of these. One of the more striking ones actually shows that there's almost a dose-dependent increase in shrinkage of the gray matter
volume and in these white matter tracts, these axons these wires as it would that
Different neurons, as a function of how much alcohol people drink. And that's also what's been seen in this recent study that I referenced at the beginning. And that's in the show. No
captions. So, again, probably the best amount of alcohol to drink would be zero glasses per week or ounces per week. For those of you drinking low amounts of
alcohol, make sure you're doing other things to promote your health. And for those of you that are drinking moderate and certainly, for those of you that are heavy drinkers, please do everything you can to move away from that and to quit
entirely. But even for
The moderate
consumers of alcohol, you are going to want to be aware of some of the negative health effects and do things to offset those if indeed, you're not going to stop drinking or reduce your intake, one of the really bad effects of alcohol, but that's
extremely well documented
is the fact that alcohol because of this toxicity of acetaldehyde and related Pathways can alter DNA methylation. It can alter gene
expression that can be many things in different tissues.
But it is associated with a significant increase
in cancer risk in particular breast cancer and in particular because breast tissue is present in both males and females. But in women, it's especially vulnerable to some of the DNA methylation changes.
Well, breast cancer in women
has a relationship to alcohol intake and alcohol intake has a relationship to breast cancer in women. In fact,
there has been proposed to be a anywhere from four.
To 13 percent increase in risk of breast cancer, for every 10
grams of alcohol consumed. How much is 10 grams? Well,
there we need to think a little bit about the
variation in the amount of alcohol and different drinks across the world,
different countries, serve different size, drinks, and have different
concentrations of alcohol in those drinks
without going down, too much of a rabbit hole and just giving you some good rules of thumb to
work. With there have been studies of the percentage of alcohol, including different drinks in the sizes of different drinks that are served in different countries.
And here's a kind of a patchwork of those
findings in Japan, one beer, one glass of wine or one shot of liquor as it served. There tends to include anywhere from seven to eight grams of
alcohol in the u.s. one beer, which generally is 12 ounces. If it's in a bottle.
One glass of wine or a shot of liquor tends to include
about 10 to 12 grams of alcohol.
And in Russia, one drink of the
very source that I just
described typically will have as much as 24
grams of alcohol
because of the differences in the concentration of
alcohols and the size of of drinks that are poured in these different countries. Okay,
of course, there are other countries in the world those countries are also vitally
important but those are the ones.
They extracted from the studies that I could find.
What does this mean? Well, what we're talking about is that for every 10 grams
of alcohol consumed, so that's one beer in the US. Maybe a little bit more than one beer in Japan or basically a third of a drink in Russia.
There's a 4 to 13 percent increase in risk of cancer.
That's pretty outrageous, right? And you might think wait how could it be that you know this stuff is even legal? Well
look, it's as I described before. It's
a toxin. It's also a toxin that people enjoy the effects of, I mean, in the u.s. at least they tried prohibition. Certainly did lead. Yes. Did lead to a reduction in alcohol, induced Health disorders in particular cirrhosis of the liver. It also led to a lot of crime because it became a substance that a lot of people still wanted.
And that people were willing to break the law in order to provide or I should say to sell and
provide. But the point is that the more alcohol people drink the greater their increase of cancer in
particular breast cancer. And
that's because of the fact that alcohol
has these effects on cells, that include changes in gene expression and cancer. That is the growth of
tumors is a dysregulation in cell cycles, right? A tumor is a aggregation or the proliferation.
Asian aggregation is stuff sticking together. By the way, proliferation is stuff, duplicating
proliferation aggregation of cells that could be a gliomas glial cells glioma, brain tumor, right? Could be
lymphoma. So within the lymph tissue, Etc,
the mutations that alcohol and Deuces to cause this are wide-ranging. Some of those are starting to start to be understood for those of you are interested in cell biology, I'll just mention that the pd-1 pathway
again. This is super specialized in for the
Leonardo's only you don't need to know
this. The pd-1 pathway seems to be upregulated and and we knew this from the discussion earlier there's a
down regulation in some of the anti inflammatory molecules that help suppress, this proliferation of cancers
nowadays there's a lot of interest in the fact that the immune system is constantly combating cancers that exists in us all the time. You know little little tumors start growing in our immune system goes and gobbles them up. Little tumors start growing the immune system.
This is inflammation. Sends out these incredible
cells. These killers b-cells and T-cells and beats them up
cancers, proliferate and take hold and cause serious problems. When the proliferation of
cells exceeds the immune, system's ability to gobble up and remove those cells. There are other mechanisms of regulating cancers, but that's one of the primary one
and alcohol hits it again is a two-hit model. It increases tumor growth
and it decreases. The sorts of molecules that suppress and combat tumor growth,
With. So again, even low to moderate amounts of alcohol, can be problematic for sake of cancers in particular breast cancers,
epidemiologists and health specialist love to try and compare different substances in terms of how bad they are.
Rarely do they compare substances in terms of how
good they are, but sometimes they do and what they'll sometimes, tell you and what you can find in the literature is that ingesting 10 to 15 grams of
alcohol day. So that would be one beer in the u.s. one.
Wine is the same as smoking 10 cigarettes, a day. Frankly, it's
hard to make that direct relationship really stick because, you know, it's a question of, you know, how long people inhale, do they have a predisposition to a lung cancer? Etc.
But even if that number
is off by, plus, or minus two
cigarettes, or even, if that number, would the equivalent of one glass of wine? Equals one cigarette per day. I think there's
General consensus now,
That
nicotine consumed by vaping or by cigarette. It's
bad for us in terms of lung cancer and other forms of cancer. And for some reason, I don't know why. Because this knowledge about alcohol and cancer in these established relationships, have been known since the late 1980s. The first, you know, kind of landmark paper on this was published in 1987. I can provide a link to that paper. It's actually quite interesting to read.
Well, the
Is there and yet, we don't often hear about it, right? In fact, in before researching this episode I had heard
before that alcohol can increase cancer risk, but I wasn't aware of just how strong that relationship is
because of the serious nature of what we're talking about. And because I would hate to be confusing or misleading to anybody. I want to just emphasize that this statistic, that there is a 4 to 13 percent, depending on which study you look at a
4 to 13 percent increase in the risk of
cancer in particular, breast cancer. For every
10 grams of alcohol consumed, that's 10 grams per day. So that's one drink per day. But I do want to emphasize that if that equates to seven drinks per week and all those seven drinks are being consumed on
Friday and Saturday. It's still averages 210 grams per
day. And I also want to emphasize that there are things that people can do to, at least partially offset
some of the negative effects of alcohol as it relates to predisposition to the formation of certain.
As of tumors and
Cancers.
I also want to be clear before I say it that doing the things I'm about to tell you is not a guarantee
that you're not going to get cancer. Nor is it a guarantee that alcohol is not going to lead to an increased predisposition for certain kinds of cancers
and the two things are consumption of folate and other B vitamins, especially, B12, you know, the consumption of folate and b12 has been shown to decrease cancer risk in
People that ingest alcohol but not completely offset it,
why? That is isn't exactly clear. It probably has something to do with the relationship between folate and
b12 and other B vitamins in gene, regulation Pathways that can lead to tumor growth.
Some point soon, we will get an expert in cancer biology and in particular in breast cancer, biology
on the program and we can ask them about this.
But I realized this is going to raise a number of questions and maybe even cause
some of you to go out.
There and start taking, folate and other B vitamins and
b12. Not incidentally, a lot of the reported hangover supplements and treatments have include folate and b12. I don't know if they have the
cancer literature in mind when they created those supplements and products I doubt they did alcohol. Really does disrupt b-vitamin Pathways both synthesis Pathways and utilization Pathways. So sometimes you'll hear, oh, you know, if you get your B vitamins, it helps you.
Cover from from Hangover more quickly. Again, the literature doesn't support that, but also again, there are a lot of
studies but more to the point, as it relates to alcohol in the formation of tumors and Cancers, it does appear
that decreased folate and other B vitamins like,
B12 are partially responsible
for the effect of alcohol and increasing cancer risk. And it does appear that consuming.
Adequate amounts of folate, and b12 might again, might partially really want a bold face and underline and highlight partially offset some of that increased risk.
There's an additional category that I want to highlight of course. And this is vitally important to State even
though it's obvious, which is that people who are
pregnant, should
absolutely not consume. Alcohol fetal. Alcohol.
Syndrome is well known and established. It's terrible.
Fetuses experience diminished brain
development, that's often permanent diminished. Limb development diminish organ development. In the
periphery meaning the heart, the lungs, the liver Etc, ingesting alcohol. While pregnant is simply a bad idea. And the reason I say this at all is first of all, it's important to include in an episode like this but
also because we can look at two things. First of all, we can look at mechanism and then we can also look at some of the lore that still sadly exists.
Out there, let's take care of the lower
that sadly exist.
First, if you look online you will sometimes be able to find
sadly that
some people believe that certain kinds of alcohol or not
detrimental to fetuses they'll say
well champagne is safe
for a pregnant mother to drink but beer is not that
is absolutely categorically.
False alcohol is alcohol. There is no evidence whatsoever that consuming certain types of alcohol is safer.
This is than others, alcohol is a toxin and the reason fetal. Alcohol syndrome exist is because the ability of that toxin to disrupt cellular processes,
remember tumor growth.
And the way that alcohol can accelerate tumor growth by proliferation of cells, the wrong cells, the ones you don't want to proliferate.
Well, all of
embryonic development, all of fetal development,
it's not the growth of a tumor. It's obviously the growth of an embryo and it's done in a very orchestrated way. I started off studying
Eating brain
development. That's where I got my Beginnings in neurobiology and I still teach embryology to medical students and graduate students. The
set of coordinated processes that has to take place from conception
to birth in order to give rise to a healthy embryo is
so. So dynamically controlled. And so exquisitely
precise with checkpoints and Recovery mechanisms and redundancy in the genes that are expressed
to make sure that if anything goes wrong, it's repaired etcetera.
Alcohol.
As a mutagen, haven't used that word yet, but a substance that can mutate DNA through alterations in DNA methylation. And these checkpoints in the cell cycle alcoholism mutagen
is one of the worst things that a developing
embryo can be exposed to and again, because its water soluble in fat soluble ingestion of alcohol. When people are pregnant passes right to the fetus.
Now, I realize that a number of people out there might be thinking, oh goodness. You know, I
didn't realize
I was pregnant until a certain stage of pregnancy and before I realized I was ingesting alcohol. Obviously
one can't undo what's been done, but I want to also emphasize that fetal alcohol
syndrome. While yes, there's a full-blown syndrome that manifests as changes in the craniofacial development that are very obvious and you can look these up. You probably seen these before the pictures before rather has to do with, I spacing for head size, a number of other features of the craniofacial development, and of course, stuff's going on in the brain
to it's a long, a
Continuum. So it is possible that some of the changes that occur are more minor. And thankfully, the
young brain in particular, the early postnatal brain is incredibly plastic. There are things that can be done in order to help recover neural circuits, that didn't develop well etcetera. But
even though it's somewhat obvious, or
should be obvious, I
really want to make clear that there's zero evidence whatsoever that
certain forms of alcohol are safer for pregnant women to ingest another's. Absolutely wrong. No one.
Pregnant should be ingesting alcohol whatsoever. And certainly if people feel like they can't avoid alcohol while pregnant, they really need to work with somebody to make sure that it just absolutely doesn't happen because it is so detrimental to the developing
fetus. Lastly, I want to talk about the
effects of alcohol on hormones and I want to distinguish between
low amounts of alcohol intake, higher
amounts of alcohol intake. And again, this chronic alcohol intake versus occasional use versus really chronic use meaning.
Alcoholic or alcoholic use disorder where people are drinking an immense amount on an ongoing basis.
The literature on alcohol and hormones is quite extensive.
And there are of course, many, many different types of hormones. The hormones that most often get mentioned and talked about on this podcast are the hormones testosterone and estrogen, which are present in both men and women in that in both men and women are important for things like libido.
They're also responsible for sexual development, actual development of the genitalia before
birth. And after birth, they're responsible for
instance, estrogen is important for memory and cognition, you never want to drop estrogen too low in men or women because it can disrupt cognition and joint health Etc
to keep this discussion relatively constrained, it's fair to say that
alcohol. And in particular, the toxic metabolites of alcohol,
increase the conversion of
testosterone to estrogen now.
This occurs in a number of different
tissues. This is not just occurring in the testes of males, this is occurring in lots of different tissues and I'll refer you to a excellent review. Will provide a link in the show notes. Captions, this is a
paper that was published in the year
2000, but the data are still quite strong. The journal is called of all
things
alcohol.
There's yes literally a journal called alcohol for the publication of data and reviews on alcohol and its effects. And the title of the paper is can alcohol. Promote aromatization of androgens to estrogens. Aromatization is this process of the
conversion of
testosterone and other androgens to estrogens through things like aromatase enzyme.
And this is a beautiful review that describes every tissue.
We're near every tissue from the ovary and females to the placenta to the liver, to the testes in, which alcohol can increase the aromatization of
testosterone to estrogen. Now,
in females, this may be part of the reason why
there's an increase in estrogen related cancers, breast cancer can be either estrogen related or non estrogen related there, other types of estrogen related cancers, outside of breast
cancer. But it appears that one reason why alcohol
increases the risk of breast cancer is because of this
Romanization from of testosterone, scuse me to estrogen in
males, accelerated, or
abnormal conversion of testosterone to estrogen can actually lead to growth of the breast tissue and males. So called gynecomastia or other effects of high estrogen or I should say of altered testosterone, estrogen ratios. Because that's really what's important.
And these can include
things like diminish, sex drive, increased fat storage and a number of other things.
That I think most people would find to be negative effects.
I once talked about the fact that drinking alcohol
can increase the aromatization of testosterone to estrogen. I posted that online
and I didn't get attacked. But I did get criticized for the fact that it has been shown. Yes, has been shown that
small amounts of alcohol, ingestion. So 5 grams or so of alcohol. Injections to be half a glass of wine or half a glass of beer
at least in some studies showed increases in
testosterone which was kind of surprising. But I
Point out other Studies have shown that
alcohol ingestion causes decreases in testosterone over time. So there's always this issue of whether not, you're looking at study of acute, exposure versus chronic exposure in one dose versus multiple Doses and exposure.
I think it's fair to say, based on my reading of the literature this review and other reviews that focus more, particularly on humans that regular ingestion
of alcohol is going to increase estrogen levels whether or not you're male or female and its
r g doing that through the romanization process by increasing the aromatase enzyme. Yes, there's some dose dependence but I think if you're somebody who's trying to optimize your testosterone to estrogen ratio, regardless of whether or not you're male or female, well, then
most certainly you're going to want to avoid drinking too much alcohol. So,
we've covered a lot of topics and data related to the mechanisms of alcohol. Hangover tolerance, cancer risk, Etc. I acknowledge that I've mainly
talk to you about the negative effects of
Whole,
I want to acknowledge that many people enjoy
alcohol in moderation, or even light, drinking the occasional drink or the occasional two drinks, or
maybe even on, average, one drink per night. So seven drinks per week. I'm certainly not here to tell you what to do and what not to do. I do find it immensely. Interesting. However,
that first of all, alcohol is a known toxin to the cells of the body. Some of you might immediately say well wait what? About
hormesis what about this phenomenon?
On where if we regularly ingest a toxin it makes
us stronger. In other words, what doesn't kill us? Makes us stronger.
Yeah, there's you know, some reason to believe that might be beneficial in terms of some forms of seller
resilience, maybe, maybe no, sorry, it doesn't work that way. There are processes of hormesis in which for instance exposing yourself
safely to increases in Adrenaline, you know, ice baths or
other things that increase adrenaline can raise your so-called stress
threshold. But here we're talking about
Cellular stress and damage to cells
so my read of the literature and again this is my read
and invite others to, you know, provide studies or I would prefer actually collections of studies that point in the direction if they exist that alcohol can be beneficial. But my reading of the literature where I should say, my understanding of what I would call the center of mass of the literature on alcohol,
is that? No consumption? Zero consumption? Consumption of
Zero ounces of alcohol
is going to be better for your health, then low to moderate consumption of alcohol and that low to moderate consumption of alcohol is going to be better for you. Of course, then moderately High to high alcohol, consumption on the order of 12 to 24 or more drinks per week.
I realized that for most people listening to this, it's
probably low to
moderate alcohol consumption.
That is part of their
Standard repertoire and I'm not here to give you justification for doing that. Nor am I going to tell you not to do that? I
would like you to consider perhaps. However, the negative effects that we understand and that are documented,
for instance, the negative effects of
alcohol, and the gut
microbiome, and the things that you can do to
better support your gut microbiome,
the negative effects on the stress
system that HPA axis that we talked about earlier, in the fact that even low to moderate levels of alcohol. Consumption can increase our
our levels of stress when we're not
drinking, and to think about,
Acquiring some tools, and, you know, getting some proficiency with tools
Behavioral or otherwise that can help you with stress, modulation that don't involve alcohol consumption.
Again, the point here is to illustrate where the problems lie with
alcohol consumption. But also what I've
tried to do is to point you to some
resources that can help offset some of those negative effects. Well, they offset all the effects. I
can't say that for sure, but certainly taking measures
to offset some of the negative effects of
Alcohol consumption that you might be having. You're doing is going to be beneficial to you and those tools and Protocols are going to be health-promoting in any case. If
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