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

- Welcome to the Huberman Lab Podcast, where we discuss science and science-based tools for everyday life. I'm Andrew Huberman and I'm a professor of neurobiology and ophthalmology at Stanford Medical School. Today we talk about

alcohol

, one of the most consumed substances on planet Earth. I should mention that both humans and non-human animals consume

alcohol

either for recreational purposes because they like the feeling it gives them or for medicinal purposes or other purposes that we will discuss. Of course, we are going to discuss the effects of alcohol on our biology, from its effects on individual cells to the organs and organ systems of our

brain

and

body

.

We will also discuss the effects of alcohol, that is,

what

being drunk actually

does

to our thinking and behavior and how it

does

it. And we're going to address

what

seems to be one of the most common questions out there: whether drinking low or moderate amounts is better for our

health

than not consuming any alcohol at all. And of course we will talk about excessive alcohol consumption, excessive alcohol consumption. We'll also talk about hangovers and what science says about ways to reduce the effects of a hangover, either by doing things that are inoculating, meaning before drinking or while drinking, as well as things to do if you have a hangover.

We'll discuss some of the genetic differences between alcohol and alcoholism, and we'll discuss youth drinking and how it can be especially harmful for reasons that I think will be quite surprising to most of you. My goal is that by the end of today's episode, you will have a deep understanding of what alcohol does to

your

brain

and

your

body

and that you will be able to make informed decisions about whether or not you should consume zero, absolutely no alcohol. , small to moderate amounts of alcohol, and again, we'll define exactly what that means, small to moderate amounts, and if you or someone you know is consuming excessive amounts of alcohol that are clearly harmful to your

health

, some of the best routes and resources that you can use to eliminate that dependency and/or consumption.

I'd like to preface all of this by saying that today's discussion is really geared toward providing you with information. It is not about judging the intake or lack of intake of alcohol. I just want you to be able to make the most informed decision possible about alcohol. I'm excited to announce that the Huberman Lab Podcast is now partnered with Momentous Supplements. We've partnered with Momentous for several important reasons. First, they ship internationally, because we know many of you are located outside of the United States. Secondly, and perhaps most importantly, the quality of their supplements is second to none in terms of both purity and precision of ingredient quantities.

Third, we have really emphasized supplements that are single ingredient supplements and that are supplied in doses that allow you to build a supplementation protocol that is optimized for cost, that is optimized for effectiveness and in which you can add and eliminate things from your protocol. in a truly systematic and scientific way. If you want to see the supplements we collaborate on with Momentous, you can visit livemomentous.com/

huberman

. There you will see those supplements and please note that we are constantly expanding the library of supplements available through Momentous on a regular basis. Again, that's livemomentous.com/

huberman

.

Before we get into today's content, I just want to answer a common question about alcohol consumption and the brain, and the question that comes up so often is whether to consume low or moderate amounts of alcohol, so maybe one drink a day. or one or two drinks a day, whether or not it is bad for the brain, in particular, whether or not it causes degeneration of neurons or nerve cells. Now, the reason this question comes up so frequently is because, for many years, it has been known that high levels of alcohol consumption, i.e. 12 to 24 drinks per week or more, certainly cause neurodegeneration, in particular of the so-called neocortex. , the outer layers of the brain that house associative memories, that house our ability to think and plan, that house our ability to regulate our most primitive impulses based on context, and so on.

So, to make it very clear, heavy drinking, that is, having three or four drinks a night every night of the week, is clearly bad for the brain. However, a recent study finally addressed the question of whether consuming low or moderate amounts of alcohol can cause brain degeneration. The title of the study is Associations between alcohol consumption and gray and white matter volumes in the UK Biobank, UK Biobank. First of all, the gray matter is the neurons, they are the so-called cell bodies that house the genome of the cells, etc., and the white matter is the connections, the fibers, the so-called axons of the neurons, and it is called white.

It matters because that tissue is surrounded by a fatty tissue called myelin, which allows nerve cells to communicate with each other very quickly. So what this study did was look at the brains, both gray matter and white matter, of more than 30,000, and even more than 35,000 generally healthy middle-aged and older adults in the United Kingdom who drank various amounts of alcohol. . . What they found was that even for people who drank low to moderate amounts of alcohol, that is, one or two drinks per day, there was evidence of thinning of the neocortex, that is, loss of neurons in the neocortex and other regions of the brain. .

And I don't say this to cause alarm. I tell you this because it is important data because it reveals and, in fact, answers the question that has been burning for so long: whether or not chronic alcohol intake can alter 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, they think of high levels of any intake, okay? So they think 5 drinks a night or 10 drinks a night or people drinking every night. Now, in this study, they looked at people who, on average, drank one or two drinks a night.

So it could be 14 drinks on the weekend, it could be one drink a night. It could be seven drinks on Friday, so on average one or two drinks a night. And I think a lot of people drink 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 consume even just seven glasses of wine during the week, there is likely to be some degeneration of your brain in response to that alcohol intake. Although, as mentioned above, we will talk about some of the things that can inoculate against some of that neuronal loss.

For those of you who are interested in reading the study in more detail, we have included a link in the titles of the show notes. Before we begin, I would like to emphasize that this

podcast

is independent of my teaching and research duties at Stanford. However, it is part of my desire and effort to bring zero-cost 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

podcast

. Our first sponsor is Levels. Levels is a program that allows you to see how different foods affect your health by giving you real-time information about your diet through a continuous glucose monitor.

One of the most important characteristics of our immediate sense of well-being and our ability to concentrate, think, move and have energy, as well as our long-term health, is our blood glucose levels. That is, our blood sugar levels. And that is because all the cells and tissues in our body and especially the neurons, the nerve cells, depend on glucose for fuel. I realize that some of you are ketogenic and, yes, you can use ketones for fuel, but the vast majority of people use glucose for fuel in their cells. If you want to maintain energy and focus throughout the day, you want to keep your blood glucose level stable and you don't want it to get too high or too low, so you need to understand how different foods and indeed how different activities they impact. your blood glucose.

I started using Levels about a year ago as a way to understand how different foods, exercise, supplements and food and exercise combinations and even sequencing, when I do what and how that affects my blood glucose levels. It has been tremendously informative. It completely changes when I exercise, how I exercise, when I eat in relation to exercise, etc. So if you're interested in learning more about Levels and trying a continuous glucose monitor yourself, visit levels.link/huberman. Again, that's levels.link/huberman. Today's episode is also brought to us by Eight Sleep. Eight Sleep makes smart mattress covers with cooling, heating, and sleep tracking capabilities.

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Again, that's ROKA, roka.com, and enter the code huberman at checkout. Let's talk about alcohol and simply recognize that humans have been consuming alcohol for thousands of years. If you look at the archaeological evidence from Mesopotamia, you will find that 5,000 years ago, people had wine vessels. Or if you want to know when people started distilling alcohol, to people's surprise, that didn't first take place in Ireland, and that's no joke on the Irish. You'll see many claims online that the Irish were the first to distill alcohol, but in reality, they weren't. The Chinese were the first to distill alcohol, and that happened in China in the 1st century.

Alcohol has been used for nutritional purposes, so there are cultures that believe, and in fact still believe, that the calories in alcohol are useful, although later we will talk about how alcohol calories are actually empty calories and what an empty calorie actually is. why it is called void. Alcohol has been used medicinally because it effectively kills bacteria and as you will soon discover, the fact that it kills bacteria, because that is absolutely true, it also kills the good bacteria in the gut and destruction. of those good bacteria in the gut can cause things like leaky gut syndrome and have all kinds of problems, and there are ways to deal with those problems and we'll talk about them.

So, alcohol has been used for medicinal purposes, it has been used to clean surfaces, it is used in my laboratory to prepare so-called reagents to make ourexperiments, but most humans have been consuming alcohol to change their internal state. to feel different than they would otherwise feel. That feeling of being drunk, inebriated, tipsy, or dazed is something that many, not all, but many humans seem to enjoy and pursue even though it usually leads to a feeling of being less happy, less motivated, more stressed, etc. , when the effect of alcohol wears off. That's pretty amazing, right? I mean, we're talking about a substance that people have been very motivated to consume, that they are still very motivated to pursue, create and consume, that they will spend money on, and that even though it makes them feel good and then they It makes you feel bad.

Now, some of you might be saying, "Well, I drink, but I don't drink excessively and therefore I don't feel bad. I feel good when I drink and then it wears off and allows me to drink." . spend the night and the next morning I'm ready to go." Well, that may be true, I believe in those people and, as I mentioned at the beginning of the episode, I'm not here to demonize alcohol in any way. But I do want to point out that It's alcohol and how it creates the effects that it produces, and then I want to talk about what those effects are when you consume alcohol even as often as one or two nights a week, or let's say...

Let's say you're just someone who has a drink or two every day. Friday, maybe a few more on Saturday, or maybe you're someone who consumes all your alcohol one night a week or one night a month. We'll talk about how that's affecting your biology. So let's address what alcohol is and how it affects the cells, tissues and organs of your body. Then we'll look at some of the epidemiology, meaning how many people consume alcohol and how much they drink. And I think then you'll be able to have a good idea of ​​how much alcohol you're drinking, if any.

If you drink anything, it's impacting your brain and your body and the decisions you may want to make about how and when to drink alcohol, or even whether you want to cut out alcohol altogether. Okay, some basic chemistry and biology of alcohol, and again, I'm going to make this very clear even if you don't have a background in chemistry and biology. Due to the structure of alcohol, it is what is called water-soluble and fat-soluble. Translated into what is meaningful to you, what that means is that when you drink alcohol, it can pass into all the cells and tissues in your body.

It has no problems going directly to those cells. So unlike many substances and drugs that actually attach to the surface of cells, to receptors, as they're called, little parking spots, and then trigger a series of downstream effects, like cascades of domino effects, Alcohol actually has its own effects. direct effects on cells because it can actually pass into those cells. Therefore, it is water and fat soluble, and the fact that it can pass into so many organs and cells so easily is what really explains its damaging effects. I should mention that there are three main types of alcohol.

There are isopropyl, methyl and ethyl alcohol, and only the last one, ethyl alcohol or ethanol, is suitable for human consumption. Still toxic though, okay? It produces stress and substantial damage to cells. I wish I could tell you otherwise, but that's just a fact. Ethanol causes substantial damage to cells, and it does so because when ethanol is ingested, it has to be converted into something else because it is toxic to the body. And there's a molecule inside all of us called NAD, and you may have heard of NAD because it's quite popular, there's a lot of discussion about NAD in the longevity literature right now.

NAD is present in all of our cells from birth to death. NAD levels tend to decrease throughout life. There are ideas that increasing NAD levels can prolong lifespan. Much of this remains controversial or, at least we should say, ongoing in terms of research. However, when ethanol is ingested, NAD and related biochemical pathways are involved in converting that ethanol to something called acetaldehyde, which breaks down into acetaldehyde. And if you thought ethanol was bad, acetaldehyde is particularly bad. Acetaldehyde is poison. It will kill the cells. It damages and kills cells and does not discriminate which cells it damages and kills.

Now, that's a problem, obviously, and the body solves it by using another component of the NAD biochemical pathway to convert acetaldehyde into something called acetate. Acetate is actually something that the body can use as fuel. And that process of going from ethanol to acetaldehyde and acetate involves the production of a toxic molecule, right? Again, acetaldehyde is really toxic. And NAD, and if we want to be technical, it is the ratio of NAD to NADH, and that chemical step is the rate-limiting step of ethanol metabolism. What does that mean for you? What that means is that if your body can't make this conversion from ethanol to acetaldehyde to acetate fast enough, well, the acetaldehyde will build up in your body and cause more damage, so it's important that your body can make this conversion. very quickly. quickly.

And the place where it does that is inside the liver, and the cells inside the liver are very good at this conversion process, but they are cells and they are exposed to acetaldehyde in the conversion process, so the cells inside the liver actually take a beating in the events of alcohol metabolism. So the key thing to understand here is that when you ingest alcohol, you are, yes, ingesting a poison, and that poison becomes an even worse poison in your body, and a percentage of that worse poison becomes a form of Calories that you can use to generate energy, generate ATP.

And the reason alcohol is considered empty calories is because the whole process is very metabolically expensive, but there is no real nutritional value to the calories it generates. You can use it for immediate energy, but it cannot be stored in any meaningful or beneficial way. It does not provide any vitamins, it does not provide any amino acids, it does not provide any fatty acids, they are truly empty calories. I know some people say sugar is empty calories, but sugar is actually a much better fuel source than alcohol or acetate. But still, when alcohol is ingested, a percentage becomes a worse poison and another percentage becomes a fuel source.

Now, the important thing is to understand that it is the poison, acetaldehyde itself, that produces the effect of being drunk or drunk. I think most people don't realize that being drunk is actually a poison-induced alteration in the way neural circuits work. So we should ask ourselves what neural circuits, what areas of the brain, what areas of the body are involved in feeling drunk or inebriated. Now, as I think about this state of being drunk or happy or very drunk or a little drunk, I want to mention something that I think most people don't know, and that is the fact that for people who drink regularly or who have a genetic predisposition to alcoholism, when they drink, they tend to feel very energetic and good for longer periods of time.

Again, people who have a genetic predisposition to alcohol or people who are chronic or even, if you remember, chronic drinkers, it doesn't have to mean a ton of alcohol, but they drink one or two a night or every other nightly drinker. or Thursday through Sunday, such people generally experience an increase in alertness and mood when they drink, while occasional drinkers will have a shorter, that is, less long-lasting period of feeling good when they drink and then a faster transition. In a state where they are tired or begin to lose motor skills, they begin to slur their words.

I also want to emphasize that this is different from tolerance. We will talk about tolerance later and what exactly tolerance means. But I really want to highlight the fact that when people ingest this poison, because it is indeed 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 predisposed to alcoholism. most frequent drinkers by the outline or timing of the different effects. And, again, the people who tend to feel more alert and excited every time they drink, they tend to feel really lively, they become kind of the life of the party and that lasts a long time, those people are the ones who really have to be careful. with a predisposition to alcoholism.

And those people also need to be careful about their drinking and how much they drink, even if they are not full-blown alcoholics. Now, of course, people who drink alcohol and who are not used to drinking alcohol have to worry about drinking alcohol for other reasons, because it can affect motor function and judgment and so on. But when you think about the biochemical effects of alcohol and what it does to the body, what it does in all cases is it's consumed in the gut, right? It goes to the stomach, the liver immediately starts this conversion that we talked about before from ethanol to acetaldehyde and acetate, and a certain amount of acetaldehyde and acetate reaches the brain, crosses the blood-brain barrier.

Again, the brain has this fence around it that we call the blood-brain barrier or BBB. Many things, most things, fortunately, cannot cross the blood-brain barrier, but alcohol, because it is soluble in water and fat, simply crosses this barrier and enters the middle, the environment of the brain, which is composed by a couple of different main cell types, neurons, nerve cells, and the so-called glial cells, which are in between the nerve cells, and we'll talk about the effects on each of those soon. So what happens when alcohol enters the brain and makes us feel dizzy or drunk and, in some people, makes people feel especially energized and happy?

Well, alcohol doesn't discriminate as to which areas of the brain it reaches. Again, it does not bind to particular receptors, but appears to have a propensity or affinity for particular brain areas that are involved in certain types of thinking and behavior. So one of the first things that happens is that there is a slight suppression, at least after the first or second drink, in the activity of the neurons in the prefrontal cortex. This is an area of ​​your neocortex that is involved in thinking and planning and, perhaps most of all, suppressing impulsive behavior. So if you go to a party and they serve alcohol and people consume drinks, what you'll notice is that within a few minutes of that party, the volume of people's voices will increase, and that's because people are just not there. paying attention. to the modulation of your voice, and as other people start to speak louder, other people speak louder.

We've all had this experience, right, of going to a party and then you walk out for a moment and you're like, "Oh my God, I was screaming." You come home and the next day your throat hurts. It could be that you've contracted some kind of virus, some virus or something, but a lot of times it's just the fact that you've been screaming all night just to be heard because when the prefrontal cortex shuts down, people stop modulating their level. of speech. almost as. You also notice that people start to gesture more, people start to stand up and sit down more, they start to walk more, if there is music, people may start to dance spontaneously.

This is all because these areas of the prefrontal cortex normally provide what is called top-down inhibition. They're releasing a neurotransmitter called GABA in various parts of the brain that are involved in impulsive motor behavior and thought patterns, and as the prefrontal cortex closes, that GABAergic suppression of impulses starts to be released, so people will say things they want to say without thinking too much about what they're saying, or they may do things they want to do without thinking about it as much or they may not even remember thinking about it at all, or experience, I should say, thinking about it.

We haven't talked about fainting yet or the effects of alcohol on memory, but while we're at it, I'll just tell you that alcohol has a very strong effect on suppressing the neural networks that are involved in memory formation. . and storage. That's why we often forget the events of a night out if we've been drinking. One of the most important things to know about the effects of alcohol on the brain is this alteration in top-down inhibition, but also, that the areas of the brain that are involved in flexible behavior, in some ways consider different options, as I could. do A or I could do B, I could tell them this or I could say that, I could say it that way or I could say it this way, this could be a little more discreet, those areas of the brain basically shut down completely and people just tend to say what you want to say.

So the key thing to understand is that when people drink, the prefrontal cortex and top-down inhibition decrease, that isThat is, habitual behavior and impulsive behavior begin to increase. Now, the interesting thing is that 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 people drink, there are changes in those drinks. circuits underlying habitual and impulsive behavior. It's really important to highlight this, so much so that I want to delve a little deeper into it. For the person who drinks, say, every Thursday night or every Friday night or goes out only on Saturday but every Saturday, there is evidence that there are changes in the neural circuits in the brain that control habitual behavior and impulsive behavior, and are modified. and strengthened in a way that makes those people more habitual and more impulsive outside of the times when they drink, and when they drink, impulsive and habitual behavior tends to increase even more.

This is something that is not often talked about when discussing the effects of alcohol. I mean, we all know the effects of being drunk can be bad, right? It can be bad in terms of judgment, motor coordination, certainly drunk driving is a terrible thing, it can cause you or other people to die, etc. But we rarely hear about changes in neural circuits after just one or two nights of regular drinking. Again, chronic drinking doesn't necessarily mean you do it every day and night. You could be the person who just 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, that is, an increase in impulsivity and habitual behavior, because the brake on those behaviors has been removed while drinking, but also changes in the neural circuits themselves that allow the usual habit. and that impulsive behavior occurs more easily even when they are not drinking. And if you want to know the actual substrate for that, the cellular substrate, I can briefly describe it. It's really interesting. Again, you don't need to know anything about biology to understand this. What it does is increase the number of synapses, the actual connection points in neural circuits that control habitual behavior.

So there is literally a growth of neural circuits in your brain that lead to the execution of existing habits, all right, the performance of things that you already know how to do, and a reduction in neural circuits, or should I say a reduction in the number . of the synapses, of the contacts, within the neuronal circuits that control behavior. So this, again, is an aspect of alcohol consumption that is not often discussed. Fortunately, it is reversible. So, in animals or humans who undertake a period of abstinence of two to six months, these neural circuits return to normal, except in cases where people have been chronically drinking large volumes of alcohol for many, many years.

And in those cases, while there is some recovery of brain circuits after people become sober—that is, completely sober, they stop drinking altogether—there is evidence of a lasting impact of heavy drinking over the course of a lifetime. life. But of course, this doesn't mean that anyone who suffers from alcoholism or who previously suffered from it shouldn't continue to focus on their health. You absolutely should. Not everything is lost. But for people who have been drinking for many years, maybe they went to college and drank a lot in those years and their neural circuits changed, if there is a period where they don't drink alcohol, again, from two to after six months. or, ideally, more, those neural circuits can be 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 now, we're limiting the conversation to people who drink, on average, one or two drinks a night. Now, some people might think that two drinks a night is a lot, and a lot of that will depend on body weight. So, for example, for people who weigh 110 pounds, ingesting two alcoholic drinks will be substantially different in terms of biochemical effects than for someone who weighs 220 pounds. Of course, tolerance also influences this, genetic background also influences this, and in fact whether people have eaten or not influences this, so there are many factors and we will talk about that.

At the moment, if you're curious about how food affects the effects of alcohol and your feeling of being drunk, you may have heard, for example, that if someone is drunk and wants to sober up, they should eat something. Turns out that doesn't work. However, that's how it works. If you eat something before drinking alcohol or while drinking alcohol, it will decrease the absorption of alcohol into your bloodstream. In other words, you won't feel as drunk as quickly. For many of you, this probably won't come as a surprise, especially if that meal includes carbohydrates, fats, and proteins, okay?

The inclusion of all three major macronutrients appears to slow the absorption of alcohol into the bloodstream much more than the presence of one or two of those macronutrients. Now, if you are already drunk or you have had a glass of wine or a beer and you eat something, the alcohol has probably already reached your bloodstream because it passes into your bloodstream very quickly. Again, it's fat-soluble and water-soluble, so in a matter of minutes, right? If you have an empty stomach, within five to 10 minutes, the alcohol will be in your bloodstream and distributed throughout your body, perhaps even faster depending on the type of alcohol and your metabolism.

But if you're already drunk and you eat something, it won't sober you up any faster, but it will certainly blunt the effects of any additional alcohol you may consume. And if you're someone who worries about getting drunk too quickly, even from a small amount of alcohol, having some food in your gut can certainly be beneficial. Now, that's food, alcohol, and alcohol absorption, but let's get back to talking about the biochemical and neurochemical effects of alcohol on the brain. We talk about top-down inhibition and we talk about circuits of habitual and impulsive behavior. Dramatic changes also occur 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, particularly those involved in mood and feelings of well-being. Recently, there has been a lot of interest in serotonin due to a published study that demonstrated quite conclusively that serotonin levels cannot really explain depression and depression-like symptoms. I want to be very clear that although that study showed that serotonin levels are not necessarily associated with depression, many interpreted the study to mean that SSRIs, selective serotonin reuptake inhibitors, which have the net effect of increasing serotonin , Yes they are. things like Prozac, etc., that those medications are somehow not helpful because they increase serotonin and serotonin is not involved in depression.

That logic doesn't really hold up so I'm going to use this as an opportunity to clarify what really happened there, and then we'll talk about how serotonin relates to alcohol consumption in things like feeling good and in depression. The key is this: SSRIs can help relieve depression. That's how it is. SSRIs can help relieve depression. They are often, but not always, associated with side effects, the dosage is very important, etc. But they probably contribute to the relief of depression by changing neural circuits, not necessarily by increasing serotonin itself. That is, increasing serotonin with these drugs likely changed the neural circuits involved in mood, allowing people to feel better through so-called neuroplasticity, which is the brain's ability to change itself in response to experience. .

So there's a little bit of confusion and, again, I'm using this episode about 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 talk about this out there that when people are depressed , it is not necessarily because serotonin levels are low. However, if serotonin levels are increased with products like Prozac, Zoloft, and other SSRIs, there is often, yes, relief from depression, but it is probably not due to restoration of serotonin levels per se. That's probably because serotonin facilitates the changes in neural circuits that need to occur for people to feel an elevated mood, okay?

So, again, this is a bit of a tangent and aside, but I think it's vital for people to know. Again, if you are thinking about taking SSRIs or are currently taking them and heard this news, definitely talk to your doctor. Again, some of these SSRIs are very useful, and also in conditions like OCD, they have been shown to be very beneficial, so we really don't want to rule out SSRIs as a potentially valuable treatment. Going back to the effects of alcohol on serotonin, it is very clear, without a doubt, that many of the circuits in the brain that are involved in mood and feelings of well-being and also in the type of self-image and how we We see ourselves using the neuromodulator serotonin and alcohol, when we ingest it and it turns into acetaldehyde, that acetaldehyde acts as a toxin in the synapses, the connections between these serotonergic neurons and many other neurons.

In other words, when we drink alcohol, the toxic effects of alcohol alter those mood circuits, initially making them hyperactive. That's right, making them hyperactive. That's why people become very talkative, people start to feel very good after a few sips of alcohol, at least most people. And then as they drink more alcohol or the alcohol wears off, serotonin levels and the activity of those circuits really start to decline, and that's why people feel less good. And usually what they do is go have another drink and try to restore that sense of well-being and mood. Now, typically what happens is that by the time people have that third and fourth, maybe even the fifth drink, there's absolutely zero chance that they're going to get that energized mood back, right?

Most people, as they drink more and more, will begin to feel more and more repressed. The forebrain is now closing quite a bit, a lot of the motor cortical areas that control coordinated movement and deliberate movement are starting to close, so people start slurring their words, people start shuffling their feet, people forget their posture. , people start leaning on things, people start passing out on couches. There is a great depression, not a depression of the psychiatric depression type, but a depression of alertness and excitement, and eventually people faint. Now, I said most people because there is a subset of people who have genetic variants or who are chronic drinkers or who are chronic drinkers and have genetic variants that, when they have the third, fourth, and fifth drink, what happens?

They become more alert, they start to talk more, they feel great, they have all kinds of ideas about how to have fun that night. And they're the ones that, if you've ever fallen asleep at a party for whatever reason, or you're getting tired and you're yawning, you look around the room and these people are still drinking. and partying and are having what appears to be an incredible time, often, not always, those are the future alcoholics in the room, or those are the people who have a genetic predisposition to alcoholism, or those are the chronic drinkers, the people who have developed enough tolerance or who have the chemical genetic makeup such that increasing amounts of alcohol make them feel better and better.

And, of course, they also have a threshold beyond which their nervous system will begin to slow down and they will faint, fall, etc., but that threshold is much, much higher than for most people. Now, this is important to understand, and it's important to understand because I think everyone should know and recognize their own predisposition and type of risk in terms of developing alcoholism. It is also important to understand it because it is related to the blackout phenomenon. Many people think that passing out is passing out, but a drunken pass out is when people drink and talk and do things; sometimes, sadly or tragically, they often drive home or walk home or get on a bike and ride home or go swimming in the ocean, all, of course, very dangerous activities when people are very drunk, or even a little drunk in some cases.

So these people do these kinds of things and they do them because they have the energy to do them and they feel good while they do them, but they do them while the activity of the neurons in the hippocampus, which is involved in memory formation,They are completely off. And that's why the next day you tell them, "Hey, maybe we should talk about what happened last night." Like, "What happened last night?" You said, "Well, do you remember going to the party?" "Yeah, I know, it was great. We did this, we did this." "Then what?" And suddenly it becomes very clear that they don't remember all the things they were doing even though they were awake.

Now, I wish I could tell you that there is some type of blood test or other biomarker or even a fingerprint test that would allow you to determine whether or not you have a propensity to be one of those drinkers with a predisposition to alcoholism. And if you've ever been completely drunk, and certainly if he's been completely drunk more than a few times, you should be pretty worried. And as we talk more about the more chronic, long-lasting effects of alcohol consumption a little later in the episode, I think it'll become clear why you should care. But in any case, there is something that can tell you whether or not you might be in that category or not, and I've already mentioned this a couple of times, but I want to make it very clear that when people drink, no matter who you are, initially there is a closure of those prefrontal cortical circuits, there is a gradual closure of the circuits that control memory, but then people split 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 couple of drinks, don't start to feel sedated. Now, of course, there will be differences created by how quickly people drink, whether or not they combine different types of alcohol, the types of alcohol, etc., but in general, that can predict whether or not you are someone who has a predisposition to alcoholism or not. An also very interesting finding is that alcohol changes the relationship between the so-called hypothalamus, the pituitary gland and the adrenal glands.

Now, the hypothalamus is a small collection of neurons about the size of a big wad of gum that sits on the roof of the mouth, and it houses neurons that are responsible for some incredible aspects of our behavior and our thinking, things like anger, things like sexual desire, things like temperature regulation, very primitive functions, including appetite, thirst, etc. Alcohol, since it can reach any part of the brain, remember that it is soluble in water and fat, has effects on the hypothalamus. The hypothalamus normally provides very specific signals to the so-called pituitary gland. This is a small gland that actually protrudes from the brain, but receives instructions from the hypothalamus.

And then the pituitary releases hormones into the bloodstream that go and talk to the adrenal glands, and the adrenal glands are located right above the kidneys in the lower back. And the adrenal glands release, as the name suggests, adrenaline, also called epinephrine, and also a molecule called cortisol, which is involved in the long-term type of stress response and also has some healthy effects on the immune system. Okay, so the hypothalamic-pituitary-adrenal 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.

I don't perceive it as stressful. People who drink regularly, so this, again, could be just one or two drinks a night or it could be someone who drinks only on Fridays or only on Saturdays or maybe only 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 the so-called stress hormone, being released at the start of the study, when they are not drinking. This is really important. People who drink a little, and when I say a little I don't mean a sip or two or even a glass of wine now and then.

I mean, again, people who maybe have one drink a night with dinner and maybe a few more on the weekend. Again, I offer a bunch of different patterns to explain how it could also be two or three drinks on Friday or six drinks on Saturday alone. Well, all of those groups experience increases in the release of cortisol from their adrenal glands when they don't drink, and as a consequence, they feel more stressed and more anxious when they don't drink. This is an effect of alcohol that is rarely talked about because so often we hear about the immediate effects of alcohol, right?

And we've been talking about some of those effects, effects like reducing the amount of stress. I mean, how many times have we heard someone say, "Ugh, I need a drink." And then they have a drink and calm down, now they can get rid of thoughts about the day's work and they can start to think about things in a perhaps more grounded or rational way, or at least believe that, or they can just relax somehow. manner. Well, while that may be true, that it can relax them, when they're not drinking, that level of cortisol that's released at the start has increased substantially.

Again, this relates to a distinct neural circuit between the brain and the body, and has to do with the ratio of cortisol to some of the other hormones involved in the stress response. We'll provide a reference to the study that describes how this all works for those of you who really want to dig into it, but let's get back to this question of those who are prone to alcoholism versus those who aren't. Remember, there are people who have genetic variants, that is, genes they inherited from their parents, that make them more likely to become alcoholics. But there are also people who drink frequently and begin to experience this increase in alertness the longer they drink during the night.

We believe that part of this effect is due to changes in this hypothalamic-pituitary-adrenal axis. So alcohol is kind of a double whammy in this sense. It is causing changes in our brain circuits and neurochemistry that, at the time we are drunk, are harmful, and it is causing changes in our neural circuits that persist long past the time we experience the sensation of being drunk or tipsy. . Now, I don't want to demonize alcohol. I'm not saying, oh, you know, if you have a glass of wine from time to time or you drink a beer from time to time or even have, you know, a drink from time to time or a drink, that's necessarily terrible for you. .

I certainly don't want that to be the message. What I'm saying is that if people chronically ingest alcohol, even if it's not every night, there are well-recognized changes in the neural circuits, there are well-recognized changes in the neurochemistry within the brain, and there are well-recognized changes. in the brain-body stress system that generally point in three directions: increased stress when people don't drink, decreased mood and feelings of well-being when people don't drink, and, as you will soon learn, changes in the brain-body stress system. neural pathways that make people want to drink even more to get back to baseline or where they were in terms of stress modulation and in terms of feelings of mood before they started drinking.

Again, I don't want to demonize alcohol, but I do want to emphasize that there are long-term plastic changes, that is, changes in neural and hormonal circuits, that, over a period of several months and certainly over a period of years of the types of drinking patterns that I described, which I think, for most people, are going to sound pretty typical, right? I mean, nothing I've described so far refers to drinking a case a night or binge drinking like we often hear about in the news. These are fairly common patterns of alcohol consumption. I mean, all you have to do is board a transatlantic flight or go to an airport on a Sunday afternoon in a sunny part of the US and, you know, people take three, four, five, six beers, etc.

Again, personal choice is a personal choice. I'm not telling you what to do. But it's very clear that those kinds of drinking patterns are changing neural and hormonal circuits, and I would love to be able to tell you that they're changing them for the better, but that's just not the case. In reality, they are changing them for the worse, and worse is defined as making people less resistant to stress, higher levels of initial stress, and lower mood overall. Before continuing with today's discussion, I would like to briefly thank our sponsor, Athletic Greens, now called AG1. Athletic Greens, also known as AG1, is an all-in-one probiotic, mineral, and vitamin drink that also has adaptogens and digestive enzymes.

I've been taking Athletic Greens since 2012, so I'm delighted that they're sponsoring the podcast. The reason I started taking Athletic Greens and the reason I continue to drink Athletic Greens twice a day is that it provides full foundational coverage of my vitamin and mineral needs, and provides important nutrients I need to support my gut microbiome. . The gut microbiome, as many of you know, supports the immune system. It also supports the so-called gut-brain axis, which is vital for mood, energy levels, regulating concentration and many other characteristics of our mental and physical health that impact our daily functioning and our high performance in any endeavor we undertake. we can perform. participate.

If you want to try Athletic Greens, you can visit Athleticgreens.com/huberman and claim a special offer. They're giving away five free travel packs, plus a year's supply of Vitamin D3 K2 with every order. And of course, vitamin D3 K2 is vital for all kinds of things, like hormonal health and metabolic health, and K2 for cardiovascular health and calcium regulation. Again, you can visit Athleticgreens.com/huberman to claim that special offer. 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 it. First of all, what kind of genes are involved in making someone fall down the path of alcoholism or not?

Well, it should come as no surprise that the genes that chronic alcohol consumption modifies tend to fall primarily into pathways related to genetic control over the serotonin receptors, the GABA receptors, remember that top-down inhibition and GABA involvement , and, Not surprisingly, the HPA, the hypothalamic-pituitary-adrenal axis. All of that, of course, combined with the environment, combines with patterns of abuse, right, we know that if you're in a social environment where a lot of people drink, the likelihood that you'll drink is much higher. , social pressures, traumas, right? Some people use alcohol to self-medicate, try to shut off their thoughts, or deal with trauma, etc.

So, they combine with the environment, but the genes that are in the serotonin synthesis and receptor synthesis pathway, GABA and HPA axes, combine with environmental pressures to give rise to alcohol use disorders. So we have a pretty coherent picture here, right? This is not a case where, for example, people who have a lot of the enzyme for metabolizing alcohol, which we'll talk about in a minute, alcohol dehydrogenase, are not necessarily the people who become alcoholics. , while certainly in certain cultures, particularly in certain Asian cultures, there are genetic differences that lead them to have low levels of alcohol dehydrogenase.

In fact, there are people who have so little alcohol dehydrogenase that when they drink alcohol they turn very red and simply feel sick. So if you're someone who takes a sip of alcohol and feels terrible, makes you nauseous, you probably have genetic variants that create a situation where you're not producing much alcohol dehydrogenase. You simply cannot metabolize alcohol, so there is a rapid buildup of the toxic effects of alcohol, acetaldehyde, and they are not converted into those empty calories. But in cultures where there are a lot of genetic variants and genes expressed in people who have a lot of alcohol dehydrogenase, of course, they can drink more and they are converting more of that alcohol from its toxic form to a non-toxic one. way, and yes, of course, more alcoholism will be seen in those communities because they drink more, but I want to emphasize that environmental factors also play a big role there, because if you can drink more, chances are you will drink more.

If you are someone who feels bad immediately after drinking, chances are you won't consume alcohol, especially if these things are genetically related, and of course genes, culture, and location in the world tend to be determining factors. together. So do you have the alcoholism gene? Well, there isn't just one gene. Chances are, if you have an immediate relative who chronically abuses alcohol or several family members who chronically abuse alcohol, well, that will predispose you to being an alcoholic. But since you don't know what genes you express unless you do genetic testing, and those things are available but most people don't do them, thisrehearsal, so to speak, and it is not a rehearsal, as we say, a rehearsal.

It is a test that is done in the laboratory to determine something, and it is not one that I recommend that you go and drink to do it, but if you have noticed that you or someone else is someone who can drink a lot during the night and has greater energy and may just drink and drink and drink, and especially if there are episodes of fainting, not remembering things from the next day despite being alert all night and so on, well, then I would be very concerned that you might actually have a genetic variant that predisposes you to alcoholism.

The other factor that predisposes to alcohol abuse is age. People who start drinking at younger ages are highly predisposed to developing alcohol dependence, regardless of their family history of alcoholism. Okay, so I'm going to repeat that. People who start drinking at a younger age are at high risk of developing alcoholism even if they do not have alcoholism in their family. Now, of course, you don't have to be an epidemiologist to understand that if you grow up in a family of drinkers and alcohol is everywhere, and especially if there is social pressure or lack of supervision, then there will be a greater tendency, or a greater probability, I should say, that you will start drinking at a younger age.

However, even people who do not grow up close to their relatives, if they start drinking at an early age, for example, at age 13 or younger, or at age 14 or 15, there is a much higher chance that they will develop a relationship. durable. alcohol dependence. People who have their first sip of alcohol later, 15, 16, or one would hope even later, I can say that one would hope because now I'm of that, you know, age and generation where, you know, you think of all the things that young people do, and you say, "Oh, God, if they would wait or refrain." Know?

It's just what happens. I don't know, there's some neural circuit for that that I can't explain yet. But people who, for example, drink only once they reach the legal drinking age, which in the US, I think in every state, is 21, if they have their first drink at 21, the The likelihood that they will develop full-blown alcohol dependence, or alcohol use disorder, as it is called, AUD, is very low. Now, a subset of them will do it because they have a very strong genetic predisposition or perhaps life circumstances create a pattern where they become chronic drinkers. But I found this very interesting.

Genes matter, but so does the age at which someone starts drinking. Now, whether or not there are changes in neural circuits as a result of alcohol consumption that make people want to seek out more and more alcohol, or whether or not there is some other effect, maybe it's a change in hormones, etc., that It predisposes those young drinkers to become chronic drinkers or even full-blown alcoholics, and they will certainly develop an alcohol use disorder. There is a definition for that. We can talk about that. It involves the amount of drinking during a certain period of time, etc.

Therefore, it is very clear that drinking at a young age creates a propensity for the development of an alcohol use disorder later in life. And while there is a genetic component in the development of alcohol use disorder, I find it very interesting that if people who have those genetic variants delay their onset of alcohol consumption, then the likelihood that they will develop alcohol use disorder Full-blown alcohol decreases as they progress. Well. Again, it's all about genes and environments. It is not one or the other and there is no single gene for alcoholism. Well, I promise I'll also talk about some of the documented positive effects of alcohol.

Although they are very few, they exist. But before I do that, I would be remiss if I didn't emphasize some of the terrible things that alcohol does and the way it does it. And for those of you who enjoy alcohol, again, I would like to say that I feel guilty telling you this because I know how much some people enjoy a good drink from time to time, and I say a good drink because some people like the taste of alcohol. alcohol. I guess I was lucky because I don't really like the taste of alcohol and it just makes me sleepy, but I know people enjoy it.

And I want to point out that there is no evidence that, you know, as long as someone is of drinking age, certainly not at the stage of brain development, that having one or two drinks every once in a while, meaning every three or four weeks or once a month, that won't cause major health problems or major health problems for most people. I guess if you have zero or very little alcohol dehydrogenase, you might feel bad, but you're probably not the type of person who will drink at all. So again, if you enjoy alcoholic beverages, I'm not trying to take them away from you in any way, but you should know what effect the beverage has if you consume it in this kind of typical chronic pattern, as we can know now.

Refer to it, which is one or two a night or a few accumulated on Friday and maybe three or four on Saturday, this type of drinking pattern, which is quite common. And one of the most serious effects that we should think about is the impact on the so-called gut-brain axis or, for the reason of today's discussion, the gut-liver-brain axis. I don't think the gut-liver-brain axis has ever been discussed on this podcast, maybe on any podcast. Although right now I say that, you know, the gut-liver-brain axis, people are going to come after me, I guess, with gut, liver and brain.

In any case, you have a brain. You have guts. That intestine goes from the throat to the end of the intestine. Your gut and your brain communicate through nerve cells, neurons and nerve connections, the vagus nerve in particular, and through chemical signals. Your gut also communicates through chemical signals and, believe it or not, also through neural signals with your liver. And, as we mentioned above, the liver is the first place where alcohol is broken down or metabolized into its components. The liver also communicates with the brain through chemical signals and neural signals, so we have the gut-liver-brain axis.

And what you discover is that people who ingest alcohol in any quantity are inducing an alteration in the so-called intestinal microbiome, the trillions of small microbacteria that reside in your intestine and that live inside you all the time and that help strengthen your system. immunological. system and they literally send signals through electrical and chemical signals to your brain to increase the release of things like serotonin and dopamine and regulate your overall mood in a positive way. Well, alcohol really disrupts those bacteria, and this shouldn't surprise us. I mean, we talked about this before and it's well known, if you want to sterilize something, you want to kill the bacteria, you put alcohol on it.

And I remember getting scraped or cut or always hurt when I was a kid, and, you know, the moment they bring out the peroxide, you're like, "Oh, boy, here it comes." But if there's no peroxide nearby and you have a wound there and you need to clean it, yes, they will use alcohol, which, by the way, I don't recommend. That's one of the hardest ways to clean a wound. But for centuries, thousands of years actually, alcohol has been used to clean things and kill bacteria. So alcohol kills bacteria and it doesn't discriminate as to which bacteria it kills, so when we ingest alcohol and it enters our gut, it kills a lot of the healthy gut microbiota.

At the same time, alcohol metabolism in the liver, which you now understand, that pathway involves NAD, acetaldehyde, and acetate, that pathway is pro-inflammatory, so it increases the release of inflammatory cytokines, things like IL-6, etc. , tumor necrosis factor alpha. If you want to learn more about the immune system, we did an episode on the immune system. You can find it at hubermanlab.com. It will teach you all the basics of what cytokines are, what mast cells are, etc. In any case, all of these pro-inflammatory molecules are being released. Now you have an alteration of the intestinal microbiota.

As a consequence, the lining of the intestine is altered and leaky gut develops, at least temporarily. That is, the bacteria that exist in the gut that are bad bacteria can now move from the gut into the bloodstream, so we have a two-way model here. In biology, we talk about two-hit models, meaning it's kind of one plus one equals four, and generally when you hear two hits, it's not a good thing. So, there are bad bacteria from partially broken down food coming out of the intestine, and the good bacteria in the intestine have been eliminated. You could say, why doesn't alcohol kill the bad bacteria in the intestine?

Well, the bad bacteria that come from partially digested foods often escape from the intestine before the alcohol can disrupt them, and now we have leaks in the intestinal wall, we have the release of these bad bacteria, we have inflammatory cytokines and other things that are released. They are released from the liver and can enter the brain through what is called neuroimmune signaling. And what's really strange, in terms of the way this manifests in the brain, I mean, it's not the way I would have done it, but, as I always say, I wasn't consulted in the design phase. and anyone who says yes should be very skeptical of him.

The net effect of this is actually to alter the neural circuits that control the regulation of alcohol consumption, and the net effect of this is increased alcohol consumption. So this is just terrible, right? I mean, if you take something that disrupts two systems, the gut microbiota, and it disrupts it in two ways: it kills the good gut microbiota and it allows the bad bacteria to move from the gut into the bloodstream, you also have proinflammatory cytokines that come from the liver and They converge or reach the brain and create a system in which 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, the types of drinking patterns that I talked about earlier, and certainly for those who are chronic heavy drinkers, what ends up It's a situation where you have inflammation in multiple places in the brain and body and the desire to drink even more and further exacerbate that inflammation and intestinal permeability. 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 who have 12 to 24 drinks a week.

For those of you who are interested in learning more about the gut-liver-brain axis and, in particular, alcohol use disorder, I will provide a link in the titles of the show notes. There is a wonderful review on this that details it. But on the positive side, it points to the possibility that at least some, again, at least some, of the negative effects of alcohol consumption, whether or not you are someone who currently consumes alcohol or who used to consume alcohol and is trying for the so-called repair of these brain and body systems, whether or not it is beneficial to replenish the intestinal microbiota.

And we know there are ways to do it, and we know there's at least some promise about this system's ability to repair itself. How do you do that? Well, I've talked about this before on the podcast, but studies done by my colleagues at Stanford, Justin Sonnenburg, who's been on this podcast as a guest, an amazing episode on the gut microbiome, and his collaborator, Chris Gardner The researchers , also from Stanford School of Medicine, have not explored alcoholism, but rather ways to improve the gut microbiota, in particular, reducing the production of inflammatory cytokines and adjusting what is called the inflammatoma.

You've heard about the genome and the proteome, etc. Well, inflammatoma is the total set or at least the almost total set of genes and proteins that control inflammation. How can you reduce inflammation and make the inflammatory healthier? Well, they have shown that you can consume two to four servings of fermented foods a day, and I'm not talking about fermented alcohol here. I'm talking about low sugar fermented foods, things like kimchi, sauerkraut, natto, for those who like Japanese food. There are other, I know, things like kefir or yogurts that have a lot of active bacteria, again, low sugar varieties of all these things.

They are fantastic for reducing inflammatory markers and improving the gut microbiome. One would imagine that whether it's getting vaccinated against some of the effects of alcohol, although frankly I'd prefer people not to drink alcohol chronically, or whether someone is trying to repair their gut microbiome because they drank a lot of alcohol or because they had a lot of these inflammatory cytokines for many years or even a short period of time, regularly ingesting two to four servings of these fermented foods can be quite beneficial. I want to be clear that this has not been specifically examined in the context of substance use disorder.alcohol, but because a large component of the negative effects of alcohol use disorder are based on this gut-liver-brain axis and the alteration of the gut microbiome. and inflammatory cytokines, it stands to reason that things that are well established to improve the state of inflammation, in other words, reduce inflammation, such as eating two to four servings of low-sugar fermented foods per day, make sense in terms of testing to repair or replace the system.

You could also imagine taking probiotics or prebiotics. That would certainly work too, although I have somewhat favored the discussion of fermented foods and replenishing the gut microbiome, mainly because there are more studies that have examined that in humans and because of the direct relationship that has been established between doing so and reducing negative markers within the inflammatoma. And I should mention that, on the topic of repair and recovery, I posted a question on Twitter the other day. I said, "What do you want to know about alcohol?" I got over 1,000 questions and I'll answer a few more a little later in the episode.

But one of the things I noticed is that a lot of the questions, hundreds, in fact, were related to the question of, well, if I drank a lot before, 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 while doing it. That I have to do? Well, it certainly should be helpful to focus a little on the gut microbiome. The other thing I should mention is that as people quit drinking alcohol, even if they're not full-blown alcoholics or have an alcohol use disorder, they need to understand that that increase in cortisol that we talked about earlier leads to a lower stress threshold and increased feelings of anxiety and stress, that will be present and will take some time to dissipate.

So for some people, it might even be helpful to realize that as they try to quit alcohol or even quit cold turkey, an increase in anxiety and feelings of stress should be expected. And in that case, I would point you to an episode we did on teacher stress. You can find it, again, at hubermanlab.com. It has a lot of behavioral tools, nutritional tools, supplement-based tools, exercise-based tools, I guess, exercise is behavioral, but a lot of tools. You can navigate to them easily because we have timestamps so you can go directly to the topic of interest.

These tools will be very useful to try to stop or control your stress. And the point here is simply that some increase in stress should be expected, and it should be expected because of that increase in cortisol that occurs even with low-level consumption but with chronic alcohol consumption. Now I would like to talk about a fairly common phenomenon, which is post-alcohol discomfort, also known as a hangover. A hangover is a constellation of effects ranging from headache to nausea to what is sometimes called anxiety, which is the anxiety that follows a day of drinking. Hangxiety, I think we can understand this physiologically if we think about the process of alcohol intake increasing the amount of cortisol and the ratio of cortisol to other stress hormones.

That explains well why some people wake up the next day or even the day after a night of drinking and feel anxious, bad and stressed for reasons they don't understand. So if you're someone who experiences anxiety, then again, I refer you to the stress master episode that we posted a while ago, and you can find it at hubermanlab.com, tools for dealing with anxiety, tools for dealing with stress, which go , again, from behavioral to nutritional to supplement-based, etcetera. That, of course, is not a justification for going out and drinking so much that you have an anxiety-induced hangover, but for those of you who are experiencing post-alcohol anxiety, so to speak, that might be a helpful resource because you certainly don't want to.

No one should experience uncomfortable amounts of anxiety, and there are great tools and resources out there. For that. Now, the other aspects of a hangover, like a stomachache or a headache or feeling sick or confused, could be related to a number of different things and are probably related to a number of different things. First of all, the sleep one gets after even one, yes, even a single glass of wine or beer, is not the same sleep one gets when there is no alcohol circulating in the system. And I'm not trying to be a downer here, but this was discussed on the episode of the Huberman Lab Podcast that I had Dr.

Matthew Walker from UC Berkeley on. And of course, Dr. Walker is a world expert on sleep, he runs one of the most prominent laboratories studying sleep and its effects, he wrote the incredible book "Why We Sleep", etc. Dr. Walker told me, and it is certainly supported by many, many quality peer-reviewed studies in animals and humans, that when alcohol is present in the brain and bloodstream, sleep architecture is altered. Slow-wave sleep, deep sleep, and rapid eye movement sleep, all of which are essential for a restful night's sleep, are disrupted. So, for those of you who drink a glass or two of wine or drink a hard liquor or beer to fall asleep, the sleep you are getting is simply not high quality sleep, or certainly not all that high quality. like the sleep you would have if you didn't have alcohol in your system.

Of course, when we talk about a hangover, we usually mean consuming more than one or two drinks. Of course, for some people, one or two drinks is probably enough to trigger a hangover, but for most people it will be having three or four, exceeding your typical limit, as it's called. Again, it's not the legal limit, that's another matter entirely. But when you drink too much alcohol, one of the reasons you feel terrible the next day is because you don't sleep well. In fact, it's not even sleeping. It is often considered pseudosleep, or at least that is what it is called in the field of sleep science, because people are in a kind of low-level hypnotic trance, it is not a real dream, there are multiple episodes of awakening, it is possible that You don't even notice that they are waking up several times.

Okay, so there are the sleep-induced effects. Then there are the altered effects of the gut microbiome, some of which we talked about earlier, so now you understand the mechanism by which alcohol destroys good, healthy gut microbiota, which then leads to a leaky gut and things like that. But one could imagine, again, you could imagine, and there is some evidence that is starting to support this, that, again, ingesting low-sugar fermented foods or perhaps even prebiotics or probiotics to support the gut microbiome could help in some of the bowel related problems. discomfort associated with a hangover. In other words, getting your gut microbiota back to a healthy state as quickly as possible, or maybe even before you drink, getting your gut microbiota back to a healthy state.

I hope you do that. I think everyone should do something to support their gut microbiome, whether or not that's eating low-sugar fermented foods daily or at least regularly, or taking probiotics or prebiotics. The gut microbiome is very important for many different things. In terms of hangovers and headaches, we know that they are caused by vasoconstriction, the constriction of blood vessels that tends to occur as a rebound after a night of drinking. Alcohol can act as a vasodilator, it can dilate blood vessels. Part of this is associated with increased so-called parasympathetic tone. We have an autonomic nervous system and it has a sympathetic component.

They are neurons that make us more alert and, if they are very active, they stress us a lot. There is also the parasympathetic aspect of the autonomic nervous system. This is all just fancy geek-speak for the parts of your brain and your body, the nerve cells that relax you a lot. When you are very relaxed, there tends to be vasodilation. It allows for greater 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 is vasoconstriction and people get brutal headaches.

That's why some people take aspirin or Tylenol or Advil or things like that, the kind of non-steroidal anti-inflammatories. I should mention that there is a lot of literature that says that some of these non-steroidal anti-inflammatory drugs are not good for us for a number of different reasons, the way they affect the liver, the way they affect the immune system, and, not surprisingly, the way how they affect the intestinal microbiome. So I'm not one to tell you what medications to take or not to take, but you'll certainly want to do a quick web search on the effects of nonsteroidal anti-inflammatories and aspirin before you start taking them or stop taking them. for that matter.

They will usually relieve the headache, but can often cause other problems, including liver problems. And keep in mind that the night after drinking, your liver has already taken a beating due to the liver's need to convert alcohol from acetaldehyde to acetate, which is now a pathway you understand well. So I'm not sure and in fact I think it's not the best idea to further overload the liver by using things that will make it have to work harder and metabolize things if the goal is to simply relieve a headache. There are many types of traditions, old school traditions, about how to get rid of a hangover.

We've already talked about how eating food won't do that, but eating food will prevent the rapid absorption of even more alcohol into your bloodstream. There is the idea that one should simply drink more alcohol. What terrible advice that is. That will only delay an even worse hangover. However, I would be remiss if I didn't say that the reason that myth arose, or that, I should say, that truth arose, because indeed drinking more alcohol will relieve a hangover but then a worse hangover. will appear, the reason that emerged is because ingesting more alcohol will cause the constricted vessels that cause the headache to dilate again.

But of course, drinking more alcohol to relieve a hangover is simply a bad idea. Just don't do it. I think this is called the hair of the dog approach. Maybe someone can put in the subtitles of the show notes on YouTube why it's called the hair of the dog. I can think of a few ideas, but they won't be very good and some of them would probably even be completely ridiculous. So don't drink more alcohol just to try to recover from a hangover. I know a lot of people have tried this before, but it's a terrible idea.

Now, one thing you'll also hear is that deliberate exposure to the cold, for example taking a cold shower, can relieve a hangover. I find this one particularly interesting because we've done episodes about the benefits of deliberate cold exposure. We have a whole episode about that. You can find it, again, at hubermanlab.com. There are direct links to some of the tools related to deliberate cold exposure and we have a complete newsletter on deliberate cold exposure protocols that you can find at hubermanlab.com, go to our Neural Network newsletter. So, those of you who are interested in ice baths and cold showers and ways to take advantage of them, you can find them there.

What you won't find there is a description of how to use deliberate cold exposure to treat a hangover. But here, I entered the literature and found something interesting. There is some evidence that increasing epinephrine levels in the bloodstream can help clear alcohol. That was very surprising to me, and I want to point out that this is not a large, robust literature, but there is some evidence that points to the fact that when levels of epinephrine, adrenaline, increase in the brain and bloodstream, some of The components of alcohol metabolism can be accelerated and some of the intoxicating effects of alcohol can be reduced, so perhaps this old habit of taking a cold shower really has something to do with it.

So when thinking about using deliberate cold exposure to reduce the effects of a hangover or to more quickly remove alcohol from the brain and bloodstream, I want to be very clear and I want to emphasize its safety. The way to do that is to understand that alcohol lowers your core body temperature, okay? It can cause slight hypothermia in people. It will lower your core body temperature. So if you were drunk and you went into a body of water, right, a pool or a lake or something, first of all, it's extremely dangerous to do it while you're drunk, right?

People drown all the time. People drown, they die as a result of doing that, so please don't do it. But also, if the water is very cold, the core body temperature will drop even more. Now, if you've heard the episodes I've done before on deliberate exposure to the cold, I'vetalked about how normally, when people don't drink alcohol, they get into an ice bath or a cold shower and their body temperature initially drops but then rebounds and rises. That is a process that will occur when people do not have alcohol in their system. When you have alcohol in your system, one of the reasons you get hypothermia is because there is a disturbance in those hypothalamic areas of the brain, in particular, the area of ​​the brain called the medial preoptic area that regulates core body temperature.

So, it's not so much that alcohol makes you cold, but that alcohol disrupts the central command centers of the brain that control temperature regulation, and that leads to mild hypothermia. So if you then get into a very cold lake or even take a cold shower or an ice bath, there is a chance that you will go very, very far down the ladder into very hypothermic territory and that can be very dangerous. Now, in terms of dealing with a hangover when the alcohol has largely been removed from your system, well, that's where some of this old tradition meets some modern science and says, well, if you can increase the adrenaline , and certainly getting into an ice bath or a cold shower or any type of cold water, as long as you can do it safely, will dramatically increase your adrenaline and, I should say, your dopamine.

That's been proven and we've talked about this on the podcast before. You get these long, drawn out increases, several hours of increases in dopamine due to deliberate exposure to the cold. By the way, it is well documented in humans. So one could imagine using deliberate exposure to the cold as a way to speed up hangover recovery. As long as it's done safely, I think there's no reason not to explore it, and if you're wondering what's safe and what temperatures to use, check out the episode on deliberate cold exposure. Therefore, cold showers could be a way to at least partially relieve a hangover.

Certainly, science from various places in literature converged to say that. But again, be careful, please, please be careful not to get into cold water when you are drunk. It is absolutely dangerous for all the obvious reasons, and it is dangerous for non-obvious reasons as well, one of which is the drastic decrease in core body temperature that can lead to dangerous hypothermia. Now, how would you go about using deliberate cold exposure to speed up hangover recovery? Well, I would look for the kind of standard protocols of, you know, one to three minutes or maybe even six minutes if you can tolerate it, or if you're really adapted to the cold, maybe do seven or ten minutes. in a cold shower, although that might be a lot.

Most people will experience a sharp surge in epinephrine, adrenaline, and a long-lasting increase in dopamine after one to three minutes of deliberate exposure to cold, ideally submerging up to the neck. Again, do this safely, please, please. , please, or a cold shower where you get as much under the shower as possible. How cold? Well, that will vary from person to person. I suggest making it as cold as it is uncomfortable so that you really want to go out but know that you can safely stay inside without, for example, having a heart attack, because if the water is very, very cold, of course it can give you a heart attack.

Most showers won't be this cold, although some probably will be. Again, be careful. Increase your adrenaline, increase your dopamine with deliberate exposure to the cold safely. Other components of a hangover that could be good targets for trying to get relief from a hangover, and here, I hope you understand why it is accurate to say that a hangover is a multifaceted phenomenon. It's not like a molecule and a receptor. There are a lot of things that happen in the brain and body. But is 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 essential electrolyte for the functioning of neurons, so making sure you have enough sodium, potassium and magnesium, the so-called electrolytes, will be important for the proper functioning of the brain and body organs. Even for people who have just had a drink or two the night before, their electrolyte and fluid balance is likely to be disturbed, and that is because alcohol also alters the so-called vasopressin pathway. I talked a lot about vasopressin and how it interacts with and controls different aspects of water retention and the release of water from the body as urine in the episode on salt.

So again, I refer to hubermanlab.com as the site where you can find that episode on salt balance and ways to restore electrolyte balance. The ideal is to have electrolytes at appropriate levels before drinking. Some people will say that for every glass of alcohol you drink, you should drink a glass of water. I would say two glasses of water would be best given the dehydrating effects of alcohol, and even better would be water with electrolytes. That would definitely set you up for a better day the next day. And if you don't manage to do that, because I guess it's a little geeky to walk around with electrolyte packets at the bar or something, although, you know, geeky, in my opinion, it's a good thing, the next day, you could take some electrolytes when you wake up, maybe even some before you go to sleep the night you drink.

So hangover is worse with disturbed sleep, worse with altered gut microbiome, worse with altered electrolytes, and worse with depletion of epinephrine and dopamine. That's why replenishing the microbiome with fermented foods, low-sugar fermented foods, that is, that's why using deliberate, safe cold exposure to increase adrenaline and dopamine, and that's why consuming electrolytes will be beneficial. The folks at examine.com, a website I really like because it has a lot of useful information, have put together a list of things that have been proposed that supposedly improve or, should I say, eliminate the effects of a hangover. And, as they point out and I would like to point out there, there isn't a lot of good science to support the idea that a compound can eliminate a hangover.

And that's probably because hangovers, again, arise from multiple organs, tissues and systems in both the brain and the body. However, they have a great list of things, from Japanese pear juice that 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 take away a hangover. The best way to solve a hangover is to make a collection of a small number of very powerful things, of which I have already listed some.

However, there are some additional things that can be done to relieve a hangover, and one of them is to be very careful about the type of alcohol you consume. So this seems interesting to me. In fact, there have been studies on what types of alcohol cause the biggest hangovers. Actually, there are also many legends and traditions about this. Some people have said, for example, that drinks high in sugar cause greater hangovers. Turns out that's not the case, or at least that's not what science points out. If you look at the expected severity of the hangover, what you find is that at the lower end of the scale there is a drink that I'm not going to tell you about, for the moment, but what you find is that it's close, for example, beer.

Beer consumption, as long as it's not excessive consumption, right, it's not far beyond the individual's tolerance, so it's one or two beers, is less likely to cause a hangover than, say, whiskey. And a glass of whiskey, or, you know, not so much whiskey as beer, of course, but it turns out that a glass of whiskey, for example, is more likely to cause a hangover than gin. Again, this is what is not showing up in 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 of the list of hangover-inducing drinks is brandy. And then one might say, "Well, doesn't brandy have a lot of sugar? Maybe it's the sugar that causes the hangover." And this is something that, again, has been discussed over and over again, that people say, "Oh, it's the high-sugar drinks that cause hangovers." It turns out, however, that when you look at alcoholic beverages, sugar content, and hangovers, at the bottom of the list is, gosh, this makes me cringe just thinking about it, is ethanol diluted in orange juice. Ugh, I can't believe people actually drink this, but ethanol diluted in orange juice.

So this isn't vodka and orange juice, okay? Vodka took third place on the list of drinks that cause hangovers. Again, this is within amounts that are comfortable for the person to drink, that they have enough experience with, or that they have the body weight to tolerate without getting very, very drunk. So the point is that if it were sugar that caused the hangover, well, then ethanol diluted in orange juice would probably be at the top of the list in terms of inducing a hangover. But it's not, it's at the bottom of the list and brandy is at the top of the list.

So what you find is that everything from ethanol diluted in orange juice to beer, vodka and gin, here I am moving up the hierarchy of things that cause hangovers, gin, white wine, whiskey, rum, wine red and then brandy. At its peak, it's kind of the world's heavyweight champion of hangover-inducing drinks; Well, what is increasing are the congeners within those drinks. Congeners are things like nitrites and other substances that give alcohol its distinctive flavor and also cause some of alcohol's intoxicating effects. Now, then you ask, "Okay, what are these congeners doing? And what are these nitrites doing?" And guess what?

While they have effects on the brain and other tissues, their primary effects are to alter the gut microbiome. So what this indicates again is that having a healthy gut microbiome and perhaps making sure to boost your gut microbiome the day after drinking is going to be especially important in preventing a hangover or at least reducing the effects of a hangover or hangover symptoms. or both. I would love to see a study on this. I can imagine designing the study myself, although this isn't really the kind of thing my lab does, but I can imagine some people taking probiotics and prebiotics, others regularly, others right after drinking, or low-sugar fermented foods, and see what The effects are expressed in terms of subjective hangover effects but also some physiological measures.

I think the way to think about hangovers in general is that, again, it represents a multifaceted, multiorgan, multitissue phenomenon, and the best way to approach it is as a multicellular, multitissue, multichemical phenomenon. freak. And before I list some of the things one could do to adjust a hangover, I think the one that appears at the top of that list, at least based on my reading of the data, is supporting the gut microbiome and certainly not drinking more alcohol. . And I guess if we were really honest with each other and asked ourselves what the best way to avoid a hangover is, it would be to not drink in the first place.

So we have covered the main effects of alcohol that lead to this state we call drunkenness or drunkenness. Again, there's a range there. You can be drunk, people can be blackout drunk, people can pass out drunk. We have also talked about hangovers and the fact that it is a multifaceted phenomenon and hangover recovery involves a multifaceted approach. Next I want to talk about tolerance. Alcohol tolerance is a very interesting phenomenon. It has roots primarily in the brain and brain systems. There is no time in the world, much less in this podcast, to address every aspect of tolerance.

There are more than 10 different types of tolerance. There is functional tolerance, chronic tolerance, rapid tolerance, there is metabolic tolerance, there is psychological tolerance. Let's keep it simple for the sake of today's discussion. And for those of you who are interested in learning about the different types of tolerance and aspects of tolerance, there is an excellent review, we will provide a link to it. This was published in 2021, so it's fairly recent, in the journal "Pharmacology Biochemistry and Behavior." By the way, or not so incidentally, that was the first magazine I published in, so I have a particular affection for it.

However, it is called Alcohol Tolerance: A Critical but Understudied Factor in Alcohol Addiction. And although this article includes alcohol addiction in the title, it's not just about alcohol addiction. Here is the basic summary of what tolerance is. First, tolerance refers to the reduction in the effects of alcohol with repeated exposure, and is caused primarily by changes in the brain's neurotransmitter systems that are a direct consequence of the toxicity of alcohol, that aldehyde molecule in the brain.that we talked about before. There are a huge number of chemicals that change with repeated exposure to acetaldehyde, from GABA to dopamine, serotonin, second messenger systems, adenosine, etc.

Rather than go into each of them in detail, I just want to talk about the outline of the tolerance-enhancing and tolerance-inducing effects of alcohol. what do I want to say with that? Well, here we go back to our old friend, that is, the molecule that appears again and again in these podcast episodes, which is dopamine. Whether someone is predisposed to alcoholism or not, whether or not they are an experienced drinker or not, when people initially start drinking, there are increases in dopamine, or what we call dopaminergic transmission. Dopamine is involved in motivation, desire, creates a feeling of well-being, increases energy, and again, usually only at the beginning of alcohol exposure.

That happens in most people as a sharp peak, like an increase. Again, if someone doesn't have alcohol dehydrogenase or they have very low levels of the enzyme that converts that acetaldehyde to acetate and that metabolizes alcohol, in other words, they're going to feel sick and unwell in a way that will negate any recognition of dopamine release. . They'll be the people who hear this and think, "Alcohol just makes me feel bad. I don't like it." Well, that's a specific subcategory of people, but most experience some kind of mild euphoria. That's why so many people drink, right? Current estimates are that in most countries, and certainly in the US, up to 80% of the adult population of legal drinking age drinks alcohol, and that number could be even higher now because in recent years There has been a trend toward increased alcohol consumption, especially after 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, there is a slow and prolonged reduction of dopamine, serotonin and related molecules in the circuits. Basically, what you get is a moment of feel-good followed by a long, slow arc of feeling not so good, which is why people usually drink over and over again throughout the night. The key thing to understand about tolerance is that with tolerance, the duration of that long, slow reduction in dopamine and serotonin becomes even longer.

In other words, the negative effects of alcohol that occur after the initial feeling of well-being last longer and actually become more intense. However, there is also a reduction in the reinforcing properties of alcohol. There is a reduction in the feeling of well-being that occurs when one ingests alcohol for the first time, and this has been measured in animals and humans. So with the first drink that someone takes, as long as it has enough alcohol dehydrogenase that they don't feel nauseous and sick right away, they feel really good. And then when the effect wears off, they feel a little bad and want to drink more so they can drink more.

With each subsequent drink, and even drinks on different nights or even different weeks, the amount of dopamine that is released is reduced and the amount of serotonin that is released is reduced. So what you're getting is less and less of the reinforcing properties of alcohol, the things that make you feel good, and more and more of the aspects of alcohol that signal pain and punishment. This is the outline of the chemical release in the brain that my colleague, the amazing Dr. Anna Lembke, who is a physician, referred to. She wrote the incredible book "Dopamine Nation." She has been a guest on this podcast, the Joe Rogan podcast, the Rich Roll podcast, and several other podcasts.

A world expert on addictions, she talked about this balance between pleasure and pain that extends beyond alcohol to things like sex and gambling and other behaviors that can potentially become addictive but certainly include alcohol. So, tolerance, it seems, is a process in which people drink more and more alcohol as an attempt to regain that feeling of well-being, but what they really get is a prolonged period of punishment, pain and discomfort from the alcohol. alcohol. Now, you might say, "Well, how does that relate to tolerance?" Well, it turns out that what they do behaviorally, and when I say they, I mean animals do this and humans do this, is they start drinking more and more in an attempt to activate those dopamine and serotonin neurons and receptors, and as they do that, there is an increase in alcohol dehydrogenase, so the enzyme that metabolizes alcohol increases because the body and the liver have to deal with all that alcohol, so now we have, again, the two-hit model .

You get fewer feel-good chemicals, more release of negative chemicals or subjective feeling patterns, I should say, and you're metabolizing alcohol faster and more easily, but that doesn't get you to a better place in your life. terms of how you feel. That is one of the main underlying reasons for what we call tolerance. So if you're someone who drinks and you notice that the high you're looking for with alcohol now requires an extra drink, or you drink plural, chances are you're disrupting the dopamine and serotonergic systems of your brain, and you are doing so. in a way that increases the pain and punishment signals that follow alcohol ingestion.

And again, that's not just the night you drink but also afterwards. Is it all bad news? Well more or less. But the good news is that if you abstain from drinking for a period of time, then of course these systems reset. How long you need to abstain will depend on how much you drank and how long you were drinking. Certainly, for people who have an alcohol use disorder or who are alcoholics, their main goal should be to give up 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 to direct anyone's recovery.

There are expert counselors, doctors and people who can work with people. In fact, for some heavy drinkers and people with severe alcohol use disorder, quitting cold turkey—that is, stopping drinking altogether—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 talking about here is people who ingest, again, between, on average, one or two drinks a night, whether they do it night after night or whether or not it's condensed for weekend use. I know many people will ask, maybe shout, "Is drinking good for me in any way?" For example, many people have probably heard that resveratrol is good for people and that red wine is rich in resveratrol.

I hate to break it to you, but the reality is that if resveratrol is indeed good for us, and there is some debate about it, some people flatly say yes, others say no, others say maybe, how much red wine would we have? that drinking to obtain enough resveratrol to promote health 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 something 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. This is confirmed by other researchers working with resveratrol and related pathways. I wish I could tell you that red wine is good for you, and in fact it might be good for you through other mechanisms. Thus, for example, studies have been carried out on low to moderate red wine consumption. This would be between one and four glasses per week. And I don't mean huge glasses, I mean six-ounce glasses of red wine. And in those cases, part of the stress reduction that can be induced by consuming red wine, perhaps some of the other micronutrients and components of red wines, particularly red wines that come from particular grapes, and this takes on a lot of nuances and, frankly, it's not well-crafted in peer-reviewed literature or certainly not in clinical trials, at least not that I know of.

Let me know if you know of a large clinical trial on this. Well, there may be some positive effects from such a low level of consumption. I'm not trying to take red wine away from anyone. I'm not trying to take anything away from anyone. However, I would be remiss if I didn't tell you that resveratrol as an argument for drinking, and drinking red wine in particular, is simply not good. It is simply not supported by peer-reviewed research. Some other things about alcohol and health. At the beginning of the episode, I referenced a study that shows that, in fact, not only excessive alcohol consumption of 12 to 24 or more drinks per week, but also light to moderate consumption of any type of alcohol, wine, beer , liquors, etc.

Reduce the thickness of the brain. It really reduces cortical thickness. In fact, it actually increases with the amount of alcohol people drink, and this has been well documented in several different studies. I can provide a link to several of these. One of the most striking shows that there is an almost dose-dependent increase in gray matter volume contraction and in these white matter tracts, these axons, these cables, if you will, that connect different neurons depending on the amount of alcohol. people drink And that is also what has been seen in this recent study that I referred to at the beginning and that is in the titles of the program notes.

So again, probably the best amount of alcohol to drink would be zero glasses per week or ounces per week. For those of you who drink small amounts of alcohol, be sure to do other things to promote your health. And for those of you who drink in moderation, and certainly for those of you who drink heavily, do your best to stay away from that and quit completely. But even moderate alcohol consumers will want to be aware of some of the negative health effects and do things to offset them if they are not going to stop drinking or reduce their consumption.

One of the really bad effects of alcohol, but one that is very well documented, is the fact that alcohol, due to the toxicity of acetaldehyde and related pathways, can alter DNA methylation and can alter gene expression. That can mean many things in different tissues, but it is associated with a significant increase in the risk of cancer, in particular breast cancer, and in particular, because breast tissue is present in both men and women, but in Women are especially vulnerable to some of the changes in DNA methylation, well, breast cancer in women has a relationship with alcohol intake, and alcohol intake has a relationship with breast cancer in women .

In fact, it has been proposed that there is a 4-13% increase in the risk of breast cancer for every 10 grams of alcohol consumed. How much is 10 grams? Well, there we have to think a little about the variation in the amount of alcohol and different drinks around the world. Different countries serve different size drinks and have different concentrations of alcohol in those drinks. So without going too far down a rabbit hole and just giving you some good rules of thumb to work with, there have been studies done on the percentage of alcohol included in different drinks and the sizes of different drinks served in different countries, and I have Here is a kind of mosaic of those findings.

In Japan, a beer, glass of wine or shot of liquor, as served there, tends to include between seven and eight grams of alcohol. In the US, a beer, which typically weighs 12 ounces if in a bottle, a glass of wine or a shot of liquor tends to include between 10 and 12 grams of alcohol. And in Russia, a drink of the different types that I just described usually has up to 24 grams of alcohol because of the differences in the concentration of alcohols and the sizes of the drinks that are served 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 I pulled from the studies I could find.

What does this mean? Well, what we're talking about is that for every 10 grams of alcohol consumed, meaning one beer in the United States, maybe a little more than one beer in Japan, or basically a third of a drink in Russia, there are 4 up to 13% increase in cancer risk. That's pretty outrageous, right? And you might think, "Wait, how is this, you know, even legal?" Well, look, as I described before, it's a toxin. It is also a toxin whose effects people enjoy. I mean, at least in the United States, they tried prohibition. It certainly led, yes, it led to a reduction in alcohol-induced health disorders, particularly liver cirrhosis.

It also led to a lot of crime because it became a substance that many people still wanted and that people were willing to break the law to provide, or rather, sell and provide. But theThe issue is that the more alcohol people drink, the greater the increase in cancer, particularly breast cancer. And that's due to the fact that alcohol has these effects on cells that include changes in gene expression, and cancer, meaning tumor growth, is a dysregulation in cell cycles, right? A tumor is an aggregation or proliferation, aggregation is things that come together, by the way, proliferation is something that duplicates, a proliferation or aggregation of cells that could be a glioma, glial cells, a glioma, a brain tumor, what?

TRUE? It could be lymphoma, that is, within the lymphatic tissue, etc. The mutations that alcohol induces to cause this are very diverse and some of them are beginning to be understood. For those of you who are interested in cell biology, I'll just mention that the PD-1 pathway, again, is super specialized and just for the amateurs, you don't need to know this, the PD-1 pathway seems to be upregulated and, As we knew from the previous discussion, there is a downregulation in some of the anti-inflammatory molecules that help suppress this proliferation of cancers. Today, there is a lot of interest in the fact that the immune system constantly fights cancers that exist in us all the time.

You know, little tumors start to grow and our immune system eats them up. Little tumors start to grow, the immune system detects the inflammation, sends out these incredible cells, these killer B and T cells, and defeats them. Cancers proliferate, take hold, and cause serious problems when cell proliferation exceeds the immune system's ability to devour and eliminate those cells. There are other mechanisms to regulate cancers, but that is one of the main ones. And the alcohol hits him. Again, it's a two-hit model. It increases tumor growth and decreases the types of molecules that suppress and fight tumor growth.

So, again, even low to moderate amounts of alcohol can be problematic for cancer, particularly breast cancer. Epidemiologists and health specialists love to test and compare different substances based on their severity. They rarely compare substances in terms of their quality, but sometimes they do. And what they will sometimes tell you and what you can find in the literature is that drinking 10 to 15 grams of alcohol a day, which would be equivalent to a beer in the US or a glass of wine, is the same as smoke 10 cigarettes a day. Frankly, it's hard to make that direct relationship really hold because, you know, it's a question of how long people inhale, whether they're predisposed to lung cancer, etc.

But even if that number is plus or minus two cigarettes apart, or even if that number were the equivalent of one glass of wine equals one cigarette per day... I think there is now a general consensus that nicotine consumed through vaping or smoking, is bad for us in terms of lung cancer and other forms of cancer. And for some reason, I don't know why, because this knowledge about alcohol and cancer and these established relationships has been known since the late 1980s. The first landmark article about this was published in 1987. I can provide a link to that article .

It's actually quite interesting to read. Well, the relationship exists and yet we don't often hear about it, right? In fact, before researching this episode, I had heard that alcohol can increase the risk of cancer, but I wasn't aware of 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 anyone, I just want to emphasize that this statistic, which is between 4% and 13%, depending on which study you look at, an increase from 4 to 13 % in the risk of cancer, in particular breast cancer, for every 10 grams of alcohol consumed, that is, 10 grams per day, that is, one drink per day.

But I do want to emphasize that if that equates to seven drinks per week and all of those seven drinks are consumed on Fridays and Saturdays, the average is still 10 grams per day. And I also want to emphasize that there are things that people can do to offset, at least partially, some of the negative effects of alcohol in terms of predisposition to the formation of certain types of tumors and cancers. I also want to make it clear before I say it that doing the things I am going to tell you is not a guarantee that you will not get cancer, nor that alcohol will not cause an increased predisposition to certain types of cancers, and both things are the consumption of folate and other B vitamins, especially B12.

You know, consuming folate and B12 has been shown to decrease the risk of cancer in people who drink alcohol, but it doesn't completely offset it. Why is not exactly clear. It probably has something to do with the relationship between folate and B12 and other B vitamins in gene regulatory pathways that can lead to tumor growth. At some point soon, we'll get an expert in cancer biology and, in particular, breast cancer biology on the show, and we'll be able to ask him about this. But I realize this will raise a number of questions and maybe even cause some of you to go out and start taking folate and other B vitamins and B12.

It's no coincidence that many of the supplements and hangover treatments included include folate and B12. I don't know if they had cancer literature in mind when they created those supplements and products. I doubt they did. Alcohol really disrupts the B vitamin pathways, both synthesis and utilization, so sometimes you'll hear, "Oh, you know, if you take B vitamins, it'll help you recover from a hangover faster." Again, the literature doesn't support that, but there aren't many studies either. But more specifically when it comes to alcohol and the formation of tumors and cancers, it seems that the decrease in folate and other B vitamins such as B12 are partially responsible for the effect of alcohol on increasing the risk of cancer.

And it appears that consuming adequate amounts of folate in vitamin B12 might, again, in part, want to highlight, underline, and partially highlight, offset some of that increased risk. There is one additional category that I want to highlight, of course, and it is vitally important to point out even though it is obvious, and that is that people who are pregnant should not consume alcohol at all. Fetal alcohol syndrome is well known and established, it is terrible. Fetuses experience a decrease in brain development that is often permanent, a decrease in limb development, a decrease in the development of organs in the periphery, i.e., the heart, lungs, liver, etc.

Drinking alcohol during pregnancy is simply a bad idea. And the reason I say this is, first of all, it's important to include it in an episode like this, but also because we can observe two things. First of all, we can look at the mechanism and then we can also look at some of the tradition that unfortunately still exists. Let's first deal with the lore that unfortunately exists. If you search the Internet, you can sometimes find, unfortunately, that some people believe that certain types of alcohol are not harmful to fetuses. They'll say, "Well, champagne is safe for a pregnant mother, but beer isn't." This is absolutely categorically false.

Alcohol is alcohol. There is no evidence that consuming certain types of alcohol is safer for fetuses than others. Alcohol is a toxin and the reason fetal alcohol syndrome exists is the ability of that toxin to alter cellular processes. Remember the growth of tumors and how alcohol can accelerate the growth of tumors by proliferating cells, the wrong cells, the ones you don't want proliferating? Well, all embryonic development, all fetal development, is not the growth of a tumor, it is obviously the growth of an embryo, and it is done in a very orchestrated way. I started studying brain development.

That's where I started in neurobiology and I still teach embryology to medical and graduate students. The set of coordinated processes that have to take place from conception to birth to give rise to a healthy embryo is so, so dynamically controlled and so exquisitely precise, with checkpoints, recovery mechanisms and redundancy in the genes that are expressed. to ensure that if something goes wrong it is fixed, etc. Alcohol as a mutagen, I haven't used that word yet, but it is a substance that can mutate DNA through alterations in DNA methylation at these cell cycle checkpoints. Alcohol as a mutagen is one of the worst things a developing embryo can be. exposed to.

And, again, because it is water- and fat-soluble, alcohol ingestion during pregnancy passes directly to the fetus. Now, I realize that a lot of people might be thinking, "Oh my gosh, you know, I didn't realize I was pregnant until a certain stage of pregnancy, and before I knew it, I was ingesting alcohol." Obviously, you can't undo what's been done, but I want to also emphasize that fetal alcohol syndrome, whereas yes, there is a full-blown syndrome that manifests itself as changes in craniofacial development that are very obvious, and you can see . These above, you've probably seen them before, or the pictures before, rather, it has to do with the space between the eyes, the size of the forehead, a number of other features of cranial facial development and of course things happen too in the brain. , is along a continuum.

So some of the changes that occur may be minor, and fortunately, the young brain, particularly the early postnatal brain, is incredibly plastic. There are things that can be done to help recover neural circuits that did not develop well, etc. But while it's obvious, or should be, I really want to make it clear that there is no evidence that certain forms of alcohol are safer for pregnant women than others. Absolutely wrong, no pregnant person should drink alcohol at all. And certainly, if people feel like they can't avoid alcohol during pregnancy, they really need to work with someone to make sure that this doesn't happen at all because it is very harmful 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 consumption, higher amounts of alcohol consumption, and again, this chronic alcohol consumption versus occasional consumption versus really chronic consumption, that is, alcohol consumption. or alcohol use disorder, in which people drink an immense amount on a continuous basis. The literature on alcohol and hormones is quite extensive, and of course there are many, many different types of hormones. The hormones that are mentioned the most and talked about most often in this podcast are the hormones testosterone and estrogen, which are present in both men and women and, in both men and women, are important for things like libido, are also responsible for Sexual development, the actual development of the genitals before and after birth, are responsible, for example, estrogen is important for memory and cognition.

It is never advisable to reduce estrogen too much in men or women because it can affect cognition and joint health, etc. To keep this discussion relatively limited, it is fair to say that alcohol, and in particular the toxic metabolites of alcohol, increase the conversion of testosterone to estrogen. Now, this occurs in several different tissues. This does not only occur in the testicles of men, but occurs in many different tissues. And I refer you to an excellent review. We will provide a link in the titles of the show notes. This is an article that was published in 2000, but the data is still pretty solid.

The magazine is called, precisely, "Alcohol", yes, literally a magazine called "Alcohol" for the publication of data and reviews about alcohol and its effects, and the title of the article is Can alcohol promote the aromatization of androgens to estrogen? ? Aromatization is this process of converting testosterone and other androgens into estrogens through things like the enzyme aromatase. And this is a beautiful review that describes every tissue, or almost every tissue, from the ovary in women to the placenta, the liver and the testes, in which alcohol can increase the aromatization of testosterone to estrogen. Now, in women, this may be part of the reason why there is an increase in estrogen-related cancers.

Breast cancer may or may not be related to estrogen, there are other types of estrogen related cancers besides breast cancer, but it seems that one of the reasons alcohol increases the risk of breast cancer is because of this aromatization of, from testosterone, sorry, to estrogen. In men, the accelerated or abnormal conversion of testosterone to estrogen can actually lead to the growth of breast tissue in men, so-called gynecomastia, or other effects of high estrogen, or should I say altered testosterone-estrogen ratios, because that's really what's important. And these may includethings like decreased sex drive, increased fat storage, and a host of other things that I think most people would consider negative effects.

I once talked about the fact that drinking alcohol can increase the aromatization of testosterone to estrogen. I posted that online and they didn't attack me, but they did criticize me for the fact that it has been shown, yes, it has been shown, that the ingestion of small amounts of alcohol, that is, five grams or so of alcohol ingestion, this Ya whether it's half a glass of wine or half a glass of beer, at least some studies saw increases in testosterone, which was kind of surprising. But I should note that other studies have shown that alcohol intake causes a decrease in testosterone over time.

So there's always the question of whether or not you're looking at an acute exposure versus chronic exposure study, you know, 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 alcohol intake will increase estrogen levels, whether you're male or female or not, and it's doing so in largely through the aromatization process, increasing the aromatase enzyme. Yes, there is some dose dependency, but I think if you are someone who is trying to optimize your testosterone to estrogen ratio, regardless of whether you are a man or a woman, then you will most likely want to do it.

Avoid drinking too much alcohol. We have covered many topics and data related to the mechanisms of alcohol, hangovers, tolerance, cancer risk, etc. I admit that I have mainly talked to you about the negative effects of alcohol. I want to recognize that many people enjoy alcohol in moderation or even a little, an occasional drink or two occasional drinks or maybe even, on average, one drink a night, that's seven drinks a week. I'm certainly not here to tell you what to do and what not to do. However, I find it immensely interesting that alcohol is a known toxin to the body's cells in the first place.

Some of you might immediately say, "Well, wait, what's up with hormesis? What's up with this phenomenon where if we regularly ingest a toxin, it makes us stronger?" In other words, what doesn't kill us makes us stronger. Yeah, there are, you know, some reasons to believe that it might be beneficial in terms of some forms of cellular resilience, maybe, maybe. I don't feel it. It doesn't work that way. There are processes of hormesis where, for example, safely exposing yourself through increases in adrenaline through, you know, ice baths or other things that increase adrenaline, can raise the so-called stress threshold, but here we are talking about cellular stress. and damage to cells.

So my reading of the literature and again this is my reading and I invite others to provide studies or I would prefer collections of studies that point in the direction, if they exist, that alcohol can be beneficial. but my reading of the literature, or should I say my understanding of what I would call the center of mass of the alcohol literature, is that no consumption, zero consumption, consumption of zero ounces of alcohol will be better for your health than consumption of low to moderate alcohol, and that low to moderate alcohol consumption will be better for you, of course, than moderately high to high alcohol consumption, on the order of 12 to 24 or more drinks per week.

I realize that for most people listening to this, light to moderate alcohol consumption is probably part of their standard repertoire, and I'm not here to give you a justification for doing it nor am I going to tell you not to do it. . However, I would like you to consider perhaps the negative effects that we understand and that are documented. For example, the negative effects of alcohol on the gut microbiome and things you can do to better support your gut microbiome, the negative effects on the stress system, the HPA axis we talked about earlier, and the fact that even low to low Moderate levels of alcohol consumption can increase our stress levels when we're not drinking, and think about getting some tools and, you know, getting some proficiency with tools, behavioral or otherwise, that can help you modulate stress. t involve alcohol consumption.

Again, the point here is to illustrate where the problems with alcohol consumption lie, but also what I've tried to do is point you to some resources that can help offset some of those negative effects. Will they compensate for all the effects? I can't say for sure, but it will certainly be beneficial for you to take steps to offset some of the negative effects of any alcohol consumption you may have or do. And those tools and protocols will promote health in any case. If you are learning and/or enjoying this podcast, please subscribe to our YouTube channel.

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