What Alcohol Does to Your Body, Brain & Health

0:00 Welcome to the Huberman Lab Podcast,

0:02 where we discuss science and science-based tools for everyday life.

0:06 [upbeat music] I'm Andrew Huberman, and I'm a professor of neurobiology

0:12 and ophthalmology at Stanford School of Medicine.

0:15 Today, we're discussing alcohol,

0:17 one of the most commonly consumed substances on the planet Earth.

0:20 I should mention that both humans and non-human

0:22 animals consume alcohol either for recreational purposes because they

0:27 like the feeling that it gives them or for medicinal

0:31 purposes or for other purposes that we'll discuss.

0:33 We are, of course, going to discuss the effects of alcohol on our biology,

0:37 ranging from its effects on individual cells,

0:40 on organs and organ systems in our brain and body.

0:43 We are also going to discuss the effects of the effects of alcohol, that is,

0:48 what being inebriated really does to our thinking

0:50 and our behavior and how it does it.

0:52 And we are going to address what seems

0:53 to be one of the more common questions out there,

0:55 which is whether or not low to moderate amounts of drinking

0:59 are better for our health than zero alcohol consumption at all.

1:03 And of course we will talk about severe alcohol intake, binge drinking.

1:08 We will also talk about hangover and what science

1:11 says about ways to reduce the effects of hangover,

1:14 either by doing things that are inoculatory,

1:16 meaning before you drink or while you drink,

1:19 as well as things to do if you happen to have a hangover.

1:22 We will discuss some of the genetic differences for alcohol and alcoholism,

1:26 and we will discuss alcohol consumption in young

1:30 people and how that can be especially

1:33 detrimental for reasons that I think are going

1:34 to be quite surprising to most of you.

1:36 My goal is that by the end of today's episode,

1:38 you will have a thorough understanding of what alcohol

1:40 does to your brain and body and that you will be able to make informed decisions

1:44 as to whether or not you should be consuming zero,

1:46 absolutely no alcohol, small to moderate amounts of alcohol,

1:50 and, again, we'll define exactly what that means, small to moderate amounts,

1:55 and if you or somebody else that you know is consuming

1:58 excessive amounts of alcohol that are clearly detrimental to your health,

2:02 some of the better routes and resources that you

2:05 can use in order to remove that dependence and/or consumption.

2:09 I'd like to preface all of that by saying

2:11 that today's discussion is really geared toward giving you information.

2:16 It is not about judging alcohol intake or lack of alcohol intake.

2:19 I just want you to be able

2:21 to make the most informed decision about alcohol possible.

2:25 I'm pleased to announce that the Huberman

2:26 Lab Podcast is now partnered with Momentous Supplements.

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3:19 Before we get into today's content in detail, I just want to answer a commonly

3:23 asked question about alcohol consumption and the brain,

3:26 and the question that so often comes up is

3:29 whether or not low to moderate amounts of alcohol,

3:31 so maybe one drink a day or one or two drinks a day kind of thing,

3:35 whether or not that is bad for your brain, in particular,

3:39 whether or not it causes degeneration of neurons or nerve cells.

3:42 Now, the reason that question comes up so often is because, for many years,

3:45 it's been known that high levels of alcohol consumption,

3:48 so 12 to 24 drinks per week or more, is certainly causing neurodegeneration,

3:55 in particular of the so-called neocortex,

3:57 the outer layers of the brain that house associative memories,

4:00 that house our ability to think and plan,

4:03 that house our ability to regulate our more

4:06 primitive drives according to context, et cetera.

4:10 So to make very clear, drinking a lot, so having, you know,

4:14 three or four drinks per night every night of the week,

4:18 is clearly bad for the brain.

4:19 A recent study, however, finally addressed the question of whether or not low

4:24 to moderate amounts of alcohol consumption can cause brain degeneration.

4:28 The title of the study is Associations between alcohol consumption

4:33 and gray and white matter volumes in the UK Biobank, the United Kingdom Biobank.

4:38 First of all, gray matter are the neurons,

4:40 it's the so-called cell bodies that house the genome of the cells,

4:43 et cetera, and white matter is the connections, the fibers,

4:46 the so-called axons of neurons, and it's called white matter because that tissue

4:52 is surrounded by a fatty tissue called myelin,

4:54 which allows nerve cells to communicate with each other very quickly.

4:57 So what this study did is it looked at the brains,

5:00 both the gray matter and the white matter, of more than 30,000,

5:04 and even more than 35,000 generally healthy middle-aged and older adults

5:09 in the United Kingdom who were drinking various amounts of alcohol.

5:13 What they found was that even for people

5:16 that were drinking low to moderate amounts of alcohol,

5:20 so one or two drinks per day, there was evidence of thinning of the neocortex,

5:27 so loss of neurons in the neocortex, and other brain regions.

5:30 And I don't say this in order to cause alarm.

5:33 I tell you this because they are important data because

5:36 they reveal and indeed answer the question that has been burning

5:40 for so long as to whether or not chronic alcohol intake

5:44 can disrupt the brain even if the chronic intake is very low.

5:47 Now, we should talk about what the word chronic means because many people,

5:50 when they hear the word chronic, think high levels of whatever intake, okay?

5:56 So they think 5 drinks a night or 10

5:58 drinks a night or people drinking every night.

6:00 Now, in this study, they looked at people who,

6:02 on average, were drinking one or two drinks per night.

6:06 So that could be 14 drinks on the weekend, it could be one drink per night.

6:11 it could be seven drinks on Friday, in other words,

6:14 on average, one or two drinks per night.

6:17 And I think many people out there are drinking somewhere between one

6:20 and two drinks per night or day of the week on average,

6:24 so that would be 7 to 14 drinks per week.

6:28 So this is an important study because it says that if

6:30 you're consuming even just seven glasses of wine across the week,

6:34 it's likely that there is going to be some

6:36 degeneration of your brain in response to that alcohol intake.

6:40 Although, as mentioned earlier, we will talk about some of the things

6:43 that can inoculate against some of that neuronal loss.

6:46 For those of you that are interested in reading the study in more detail,

6:50 we've put a link to it in the show note captions.

6:52 Before we begin, I'd like to emphasize that this podcast

6:54 is separate from my teaching and research roles at Stanford.

6:57 It is, however, part of my desire and effort to bring

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10:47 Let's talk about alcohol, and let's just acknowledge that human beings

10:49 have been consuming alcohol for thousands of years.

10:52 If you look at the archeological evidence from Mesopotamia,

10:54 you'll find that 5,000 years ago, people had wine vessels.

10:57 Or if you want to know when people first started distilling alcohol,

11:00 much to people's surprise,

11:01 that did not first take place in Ireland, and that's not a joke about the Irish.

11:05 You'll see a lot of claims online

11:06 that the Irish were the first to distill alcohol, but, in fact, they were not.

11:10 It was the Chinese that were the first to distill alcohol,

11:12 and that took place in China in the first century.

11:15 Alcohol has been used for nutritional purposes,

11:17 so there are cultures that believe,

11:20 and indeed still believe, that the calories in alcohol are useful,

11:23 although later we'll talk about how alcohol calories are

11:25 indeed empty calories and what an empty calorie really is,

11:29 why it's called empty.

11:31 Alcohol has been used for medicinal

11:33 purposes because indeed it does kill bacteria, and, as you'll soon find out,

11:36 the fact that it kills bacteria, because that is absolutely true,

11:40 it also kills the good bacteria in your gut,

11:42 and the destruction of that good bacteria in your gut can lead

11:45 to things like leaky gut syndrome and has all sorts of issues,

11:48 and there are ways to deal with those issues and we'll talk about those.

11:50 So alcohol has been used for medicinal purposes,

11:52 it's been used to clean surfaces, it's used in my laboratory in order

11:56 to make up so-called reagents to do our experiments,

11:59 but most humans have been consuming alcohol

12:02 in order to change their internal state,

12:04 in order to feel differently than they would otherwise.

12:07 That feeling of being drunk or inebriated

12:09 or tipsy or lightheaded is something that many,

12:12 not all, but many humans seem to enjoy and pursue even though,

12:17 typically, it leads to a feeling of being less happy,

12:23 less motivated, more stressed, et cetera, when the alcohol wears off.

12:28 That's pretty incredible, right?

12:29 I mean, we're talking about a substance

12:30 that people have been highly motivated to pursue,

12:32 that are still highly motivated to pursue, to create and to consume,

12:36 that they'll spend money on, and that's despite the fact that it

12:40 makes them feel good and then it makes them feel lousy.

12:43 Now, some of you might be saying, "Well, I drink,

12:45 but I don't drink to excess and, therefore, I don't feel lousy.

12:48 I feel good when I drink and then it wears

12:49 off and it allows me to get through my evening,

12:51 and then the next morning I'm ready to go." Okay,

12:54 that very well may be true, I believe those people,

12:58 and, as I mentioned in the beginning of the episode,

13:00 I'm not here to demonize alcohol in any way.

13:02 But I do want to point out what alcohol

13:05 is and how it creates the effects that it does,

13:08 and then I want to talk about what those effects are when you

13:12 engage in consuming alcohol even as often as one or two nights per week,

13:17 or let's say you're just somebody who has a drink or two on Friday,

13:20 maybe a few more on Saturday,

13:21 or maybe you're somebody who consumes all your alcohol

13:24 one night per week or one night per month.

13:25 We'll talk about how that's affecting your biology.

13:28 So let's address what alcohol is and how it

13:31 affects the cells and tissues and organs of your body.

13:33 Then we'll take a look at some of the epidemiology, that is,

13:36 how many people are consuming alcohol and how much they're drinking.

13:39 And then you will be able, I think,

13:41 to get a good sense of how the alcohol that you're drinking,

13:44 if you're drinking any at all,

13:46 is impacting your brain and body and the choices you

13:49 might want to make about how and when to drink alcohol,

13:52 or even if you want to eliminate alcohol altogether.

13:55 Okay, so some basic chemistry and biology of alcohol, and, again,

13:58 I'll make this very clear even if

14:00 you don't have a chemistry and biology background.

14:02 Because of the structure of alcohol,

14:04 it is what's called both water-soluble and fat-soluble.

14:08 Translated into what's meaningful for you,

14:11 what that means is when you drink alcohol,

14:13 it can pass into all the cells and tissues of your body.

14:17 It has no trouble just passing right into those cells.

14:20 So unlike a lot of substances and drugs

14:23 that actually attach to the surface of cells,

14:26 to receptors, as they're called, little parking spots,

14:28 and then trigger a bunch of downstreams, like, domino cascades of effects,

14:33 alcohol actually has its own direct effects on cells

14:36 because it can really just pass into those cells.

14:39 So it's water- and fat-soluble,

14:42 and the fact that it can pass into so many organs

14:44 and cells so easily is really what explains its damaging effects.

14:49 I should mention that there are three main types of alcohol.

14:52 There's isopropyl, methyl, and ethyl alcohol, and only the last one,

14:57 ethyl alcohol or ethanol, is fit for human consumption.

15:00 However, it is still toxic, okay?

15:03 It produces substantial stress and damage to cells.

15:07 I'd love to be able to tell you otherwise, but that's just a fact.

15:10 Ethanol produces substantial damage to cells,

15:14 and it does that because when you ingest ethanol,

15:17 it has to be converted into something else because it is toxic to the body.

15:21 And there's a molecule inside of all of us called NAD,

15:25 and you may have heard of NAD because it's quite popular,

15:27 there's a lot of discussion about NAD in the longevity literature right now.

15:32 NAD is present in all our cells from birth until death.

15:34 The levels of NAD tend to go down across the lifespan.

15:37 There are ideas that increasing levels of NAD may extend lifespan.

15:40 A lot of that is still controversial,

15:42 or, at least we should say, is ongoing in terms of the research.

15:45 But nonetheless, when you ingest ethanol,

15:47 NAD and related biochemical pathways are involved

15:50 in converting that ethanol into something called acetaldehyde,

15:54 it's broken down into acetaldehyde.

15:56 And if you thought ethanol was bad, acetaldehyde is particularly bad.

15:59 Acetaldehyde is poison.

16:01 It will kill cells.

16:03 It damages and kills cells and it is

16:05 indiscriminate as to which cells it damages and kills.

16:09 Now, that's a problem, obviously,

16:11 and the body deals with that problem by using another component

16:16 of the NAD biochemical pathway

16:18 to convert acetaldehyde into something called acetate.

16:22 Acetate is actually something that your body can use as fuel.

16:26 And that process of going from ethanol to acetaldehyde

16:30 to acetate does involve the production of a toxic molecule, right?

16:35 Again, acetaldehyde is really toxic.

16:37 And NAD, and if we want to get technical, it's the NAD-to-NADH ratio,

16:43 and that chemical step is the rate-limiting step to ethanol's metabolism.

16:48 What does that mean for you?

16:50 What that means is that if your body can't do

16:53 this conversion of ethanol to acetaldehyde to acetate fast enough, well,

16:57 acetaldehyde will build up in your body and cause more damage,

17:01 so it's important that your body be able to do this conversion very quickly.

17:05 And the place where it does that is within the liver,

17:09 and cells within the liver are very good at this conversion process,

17:13 but they are cells and they are

17:15 exposed to the acetaldehyde in the conversion process,

17:18 and so cells within the liver really

17:20 take a beating in the alcohol metabolism events.

17:25 So the key thing to understand here is

17:28 that when you ingest alcohol, you are, yes,

17:30 ingesting a poison, and that poison is converted

17:32 into an even worse poison in your body,

17:34 and some percentage of that worse poison is converted into a form

17:37 of calories that you can use to generate energy, generate ATP.

17:42 And the reason why alcohol is considered empty calories

17:45 is because that entire process is very metabolically costly,

17:48 but there's no real nutritive value of the calories that it creates.

17:53 You can use it for immediate energy,

17:55 but it can't be stored in any kind of meaningful or beneficial way.

17:58 It doesn't provide any vitamins, it doesn't provide any amino acids,

18:02 it doesn't provide any fatty acids, it's truly empty calories.

18:05 I know some people talk about sugar is empty calories,

18:07 but sugar actually is a far better fuel source than alcohol or acetate.

18:13 But nonetheless, when you ingest alcohol,

18:16 some percentage is being shuttled into a worse poison

18:19 and some is being shuttled into a fuel source.

18:22 Now, the important thing to understand is that it is the poison,

18:27 the acetaldehyde itself, that leads to the effect of being inebriated or drunk.

18:32 I think most people don't realize that, that being drunk is

18:36 actually a poison-induced disruption in the way that your neural circuits work.

18:40 And so we should ask ourselves, like, which neural circuits,

18:43 what brain areas, what body areas are involved in feeling drunk or inebriated?

18:47 Now, in thinking about this state of being tipsy

18:50 or happy or really drunk or a little bit drunk,

18:53 I want to mention something that I think most people aren't aware of, and that's

18:57 the fact that for people that are regular

19:00 drinkers or that have a genetic predisposition to alcoholism,

19:04 when they drink, they tend to feel very

19:07 energized and very good for longer periods of time.

19:11 Again, people who have a genetic predisposition to alcohol or people

19:14 who are chronic drinkers or even just, if you recall,

19:17 chronic doesn't have to mean a ton of alcohol but they're drinking one or two

19:20 per night or they're every other night

19:22 type drinkers or Thursday through Sunday drinkers,

19:25 those people typically experience an increase

19:28 in alertness and mood when they drink,

19:31 whereas occasional drinkers will have a briefer, meaning less long-lasting,

19:36 period of feeling good when they drink and then more quickly transition

19:40 into a state in which they're tired or they start losing motor skills,

19:44 they start slurring their speech.

19:47 I also want to emphasize this is distinct from tolerance.

19:49 We'll talk about tolerance later and exactly what tolerance means.

19:52 But I really want to highlight the fact that when people ingest this poison,

19:56 'cause indeed it is poison, the range of effects is very different,

20:01 and you can reliably predict who are the people

20:04 with a predisposition to alcoholism and who are

20:07 the people who are more regular drinkers

20:09 by the contour or the timing of the different effects.

20:12 And, again, people who tend to feel

20:15 more alert and excited every time they drink, they tend to get a real lift,

20:19 they become kind of the life of the party and that lasts a long while,

20:23 those people are the ones that really

20:25 have to be careful about predisposition for alcoholism.

20:29 And those people also need to be careful about

20:32 their drinking and the amount of drinking that they're doing,

20:34 even if they're not full-blown alcoholics.

20:37 Now, of course, people who are ingesting alcohol who are not accustomed

20:40 to drink alcohol have to be concerned about drinking alcohol for other reasons,

20:43 because it can impair motor function and judgment, et cetera.

20:46 But in thinking about the biochemical effects

20:48 of alcohol and what it's doing to the body,

20:51 what it's doing in all cases is it's consumed into the gut, right?

20:57 Goes into the stomach, the liver immediately starts this conversion that we

21:00 talked about before of ethanol to acetaldehyde to acetate,

21:02 and some amount of acetaldehyde and acetate are making it into the brain,

21:06 it crosses the blood-brain barrier.

21:07 Again, the brain has this fence around it

21:09 that we call the blood-brain barrier or the BBB.

21:12 Many things, most things, thankfully, can't pass across the blood-brain barrier,

21:16 but alcohol, because it's water- and fat-soluble,

21:19 just cruises right across this fence and into the milieu,

21:22 the environment of the brain,

21:24 which is made up of a couple different major cell types,

21:26 neurons, nerve cells, and so-called glial cells,

21:28 which are in between the nerve cells,

21:30 and we'll talk about the effects on each of those soon.

21:33 So what happens when alcohol gets into the brain

21:35 that makes us feel tipsy or drunk and, in some people,

21:38 makes people feel really especially energized and happy?

21:42 Well, alcohol is indiscriminate in terms of which brain areas it goes to.

21:47 Again, it doesn't bind to particular receptors,

21:50 but it does seem to have a propensity or an affinity for particular

21:54 brain areas that are involved in certain kinds of thinking and behavior.

21:57 So one of the first things that happens is that there's a slight,

22:01 at least after the first drink or second drink,

22:04 there's a slight suppression in the activity

22:06 of neurons in the prefrontal cortex.

22:09 This is an area of your neocortex that's

22:11 involved in thinking and planning and, perhaps above all,

22:15 in suppression of impulsive behavior.

22:18 So if you go to a party

22:20 and they're serving alcohol and people are consuming drinks,

22:23 what you'll notice is that a few minutes into that party,

22:26 the volume of people's voices will increase,

22:28 and that's because people are simply

22:29 not paying attention to their voice modulation,

22:31 and as other people start speaking more loudly,

22:33 other people are speaking more loudly.

22:34 We've all had this experience, right,

22:35 of going to a party and then you step outside for a moment and you go,

22:38 "Oh, my goodness, I was shouting." You come home,

22:40 the next day, you've got a sore throat.

22:41 It might be that you picked up some sort of bug, some virus or something,

22:44 but oftentimes it's just the fact that you've been shouting all

22:47 night just to be heard because as the prefrontal cortex shuts down,

22:50 people stop modulating their level of speech quite as much.

22:55 You also notice that people start gesticulating more,

22:57 people will start standing up and sitting down more,

22:59 they'll start walking around more,

23:00 if there's music on, people might spontaneously start dancing.

23:04 All of this is because these areas of the prefrontal

23:06 cortex normally are providing what's called top-down inhibition.

23:10 They are releasing a neurotransmitter called GABA onto various parts

23:13 of the brain that are involved in impulsive motor behavior and thought patterns,

23:17 and as you shut down the prefrontal cortex,

23:20 that GABAergic suppression of impulses starts to be released,

23:24 so people will say things that they want

23:26 to say without so much forethought about what they're saying,

23:30 or they might do things that they want to do without really thinking it

23:33 through quite as much or they might

23:35 not even remember thinking it through at all,

23:37 or experience, I should say, thinking it through at all.

23:39 We haven't talked about blacking out yet and the effects of alcohol on memory,

23:42 but as long as we're there,

23:43 I'll just tell you that alcohol has a very strong effect

23:46 in suppressing the neural networks that are

23:49 involved in memory formation and storage.

23:51 This is why oftentimes we forget the events

23:53 of a night out if we've been drinking.

23:56 One of the more important things to know about the effects

23:59 of alcohol in the brain is this disruption in top-down inhibition, but, also,

24:04 that areas of the brain that are involved in flexible behavior,

24:09 sort of considering different options, like I could do A or I could do B,

24:12 I could say this to them or I could say that, I could

24:14 say it in that way or I could say it in this way,

24:16 this might be a little more tactful,

24:18 those brain areas basically shut down entirely and people

24:22 just tend to say what they want to say.

24:23 So the key thing to understand is that when people drink,

24:26 the prefrontal cortex and top-down inhibition is diminished,

24:31 that is, habitual behavior and impulsive behavior starts to increase.

24:36 Now, what's interesting is this is true in the short term,

24:39 so after people have one or two, maybe three or four drinks,

24:42 but it's also true that the more often that people drink,

24:48 there are changes in the very

24:50 circuits that underlie habitual and impulsive behavior.

24:53 This is really important to highlight,

24:55 so much so that I want to drill into it a bit more deeply.

24:58 For the person that drinks, say, every Thursday night or every Friday night

25:02 or goes out only on Saturdays but every Saturday,

25:06 there's evidence that there are changes in the neural circuits

25:09 of the brain that control habitual behavior and impulsive behavior,

25:12 and they are modified and strengthened in ways that make those people

25:17 more habitual and more impulsive outside the times in which they are drinking,

25:22 and when they drink,

25:24 impulsive and habitual behavior tends to increase even further.

25:27 This is something that's not often talked

25:29 about when discussing the effects of alcohol.

25:31 I mean, we all know the effects of being drunk can be bad, right?

25:36 Can be bad in terms of judgment, motor coordination,

25:39 certainly driving drunk is a terrible thing,

25:41 get you or other people killed and so on.

25:44 But rarely do we hear about the changes in neural

25:47 circuits from just one or two nights of regular drinking.

25:52 Again, chronic drinking doesn't necessarily mean every day and every night.

25:56 It could be the person that simply drinks every Thursday or every Friday or just

25:59 once a week has three or four drinks or maybe even a few more.

26:03 That person is going to experience a decrease in this top-down inhibition,

26:07 so an increase in impulsivity and habitual behavior,

26:09 because the brake on those behaviors has been removed while they're drinking,

26:13 but also changes in the very neural circuits that allow habitual

26:17 and impulsive behavior to occur more readily even when they're not drinking.

26:21 And if you want to know the actual substrate for that, the cellular substrate,

26:24 I can briefly describe it.

26:25 It's really interesting.

26:27 Again, you don't need to know any biology to understand this.

26:29 What it does is it increases the number of synapses,

26:33 the actual points of connection

26:34 in the neural circuits that control habitual behavior.

26:37 So there's literally a growth of the neural circuits

26:40 in your brain that lead to existing habit execution,

26:43 all right, the performance of things you already know how to do,

26:47 and a reduction in the neural circuits,

26:49 or I should say a reduction in the number of synapses,

26:52 of the contacts, within the neural circuits that are controlling behavior.

26:56 So this, again, is a not often discussed aspect of alcohol intake.

27:00 Fortunately, it is reversible.

27:02 So in animals or humans that undertake a period

27:05 of abstinence of anywhere from two to six months,

27:08 these neural circuits return to normal except in cases where people

27:12 have been chronically drinking large volumes of alcohol for many, many years.

27:16 And in those cases, while there is some

27:19 recovery of brain circuitry after people get sober, meaning completely sober,

27:24 they stop drinking entirely, there is evidence of long-lasting impact

27:28 of heavy alcohol usage throughout the lifespan.

27:31 But, of course, this doesn't mean that anyone that's suffering from alcoholism

27:33 or that used to should not continue to focus on their health.

27:36 You absolutely should.

27:37 All is not lost.

27:39 But for people that have been drinking for a lot of years,

27:41 maybe you went to college and you drank

27:42 a lot in those years and your neural circuits changed,

27:45 if there's a period in which you don't drink alcohol,

27:47 again, from two to six months and ideally longer,

27:51 those neural circuits can then be remodified back to their original state.

27:55 So let's consider some of the other neurochemical

27:57 effects of alcohol in the brain and body.

27:59 And, again, for right now,

28:00 we're confining the conversation to people that are drinking,

28:03 on average, one or two drinks per night.

28:06 Now, some people might think that two drinks per night is a lot,

28:08 and a lot of that will depend on body weight.

28:10 So for instance, people who weigh 110 pounds,

28:15 for them to ingest two alcoholic drinks is going to be substantially

28:19 different in terms of the biochemical

28:21 effects than somebody who weighs 220 pounds.

28:24 Of course tolerance will also factor into this, genetic background

28:27 will also factor into this, and indeed whether or not

28:31 people have eaten will factor into this, so there

28:33 are a lot of factors and we'll talk about that.

28:35 For the time being, if you're curious about how food

28:37 impacts the effects of alcohol and your feelings of being drunk,

28:41 you may have heard, for instance,

28:42 that if somebody's inebriated and they want to sober up,

28:45 they should eat something.

28:46 Turns out that does not work.

28:48 Here's how it does work, however.

28:50 If you eat something prior to drinking alcohol or while ingesting alcohol,

28:55 it will slow the absorption of alcohol into the bloodstream.

28:59 In other words, you won't feel as drunk as fast, for many of you,

29:02 this probably comes as no surprise, in particular,

29:05 if that meal includes carbohydrates, fats, and proteins, okay?.

29:09 The inclusion of all three major macronutrients

29:12 seems to slow the absorption of alcohol

29:14 into the bloodstream far more than having any

29:17 one of those or two of those macronutrients present.

29:21 Now, if you are already inebriated or you've had

29:24 a glass of wine or a beer and you eat something,

29:28 chances are that alcohol has already made it

29:31 into your bloodstream because it moves into the bloodstream so quickly.

29:34 Again, it's fat-soluble and water-soluble, so within minutes, right?

29:39 If you have an empty stomach, within five to 10 minutes,

29:41 that alcohol is going to be within

29:42 your bloodstream and distributed throughout your body,

29:44 maybe even faster depending on the type of alcohol and your metabolism.

29:48 But if you're already drunk and you eat something,

29:52 it's not going to sober you up more quickly,

29:53 but it certainly will blunt the effects

29:55 of any additional alcohol that you might consume.

29:57 And if you're somebody who is concerned about getting too drunk too quick,

30:02 even from a small amount of alcohol,

30:03 having some food in your gut can certainly be beneficial.

30:06 Now, that's food and alcohol and the absorption of alcohol,

30:10 but let's go back to talking about the biochemical

30:13 and neurochemical effects of alcohol on the brain.

30:15 We talked about top-down inhibition,

30:18 and we talked about habitual and impulsive behavior circuitry.

30:21 There are also dramatic changes in the activity

30:25 of neurons that control the release of so-called serotonin.

30:28 Serotonin is a neuromodulator.

30:30 It changes the activity of neural circuits and many neural circuits,

30:34 in particular, those involved in mood and feelings of well-being.

30:37 Recently, there's been a lot of interest

30:39 in serotonin because of a study that was

30:41 released that showed pretty conclusively that serotonin

30:43 levels can't really explain depression and depression-like symptoms.

30:48 I want to make it very clear that although that study

30:51 did show that serotonin levels are not necessarily associated with depression,

30:56 the study was interpreted by many to mean that SSRIs,

30:59 selective serotonin reuptake inhibitors,

31:01 which have the net effect of increasing serotonins,

31:04 these are things like Prozac,

31:06 et cetera, that those drugs are somehow not helpful

31:10 because they increase serotonin and serotonin isn't involved in depression.

31:15 That logic doesn't really hold together so I'm going to use

31:19 this as an opportunity to just clarify what really occurred there,

31:22 and then we'll talk about how serotonin relates to alcohol

31:25 consumption in things like feeling good and in depression.

31:29 The key thing is this, SSRIs can help alleviate depression.

31:34 That's right.

31:35 SSRIs can help alleviate depression.

31:37 They are often, not always, associated with side effects,

31:40 dosage is very important, et cetera.

31:42 But they probably support relief from depression by changing neural circuits,

31:48 not necessarily by increasing serotonin itself.

31:52 That is, increasing serotonin with these drugs

31:54 likely changed the neural circuits involved in mood,

31:57 allowing people to feel better through so-called neuroplasticity,

32:00 which is the brain's ability to change itself in response to experience.

32:03 So there's a bit of confusion, and, again,

32:05 I'm using this episode on alcohol to highlight

32:08 some of the confusion because I think it's timely,

32:10 because the study just came out and there's a lot

32:12 of chatter about this out there that when people are depressed,

32:15 it's not necessarily because serotonin levels are low.

32:18 However, if serotonin levels are increased with things like Prozac,

32:22 Zoloft, and other SSRIs, oftentimes there is, yes, a relief from depression,

32:27 but that's probably not because of restoring serotonin levels, per se.

32:31 It's probably because serotonin facilitates

32:34 the changes in neural circuits that need

32:37 to occur in order for people to feel elevated mood, okay?

32:40 So, again, that's a bit of a tangent and aside,

32:42 but I do think it's a vital one for people to know about.

32:44 Again, if you're thinking about taking SSRIs or you're

32:47 currently taking them and you've heard this news,

32:48 definitely talk to your doctor.

32:50 Again, there is great utility for some of these SSRIs,

32:52 and, also, in conditions like OCD, they've been shown to be very beneficial,

32:56 so we really don't want to throw SSRIs out as a potentially valuable treatment.

33:01 Getting back to the effects of alcohol on serotonin,

33:05 it's very clear, beyond any doubt,

33:08 that many of the circuits in the brain that are involved in mood and feelings

33:12 of well-being and also sort of self-image

33:15 and how we see ourselves employ the neuromodulator serotonin,

33:19 and alcohol, when we ingest it and it's converted into acetaldehyde,

33:25 it goes and that acetaldehyde acts as a toxin at the very synapses,

33:31 the connections between these serotonergic neurons and lots of other neurons.

33:34 In other words, when we ingest alcohol,

33:36 the toxic effects of alcohol disrupt those mood circuitries,

33:40 at first making them hyperactive.

33:42 That's right, making them hyperactive.

33:43 This is why people become really talkative,

33:46 people start to feel really good after a few sips of alcohol,

33:48 at least most people do.

33:50 And then as they ingest more alcohol or as that alcohol wears off,

33:54 serotonin levels and the activity of those circuits really starts to drop,

33:58 and that's why people feel less good.

34:00 And typically what they do, they go and get another drink and they attempt

34:04 to kind of restore that feeling of well-being and mood.

34:06 Now, typically what happens is that as people ingest the third and fourth,

34:10 maybe even the fifth drink,

34:12 there's an absolute zero chance of them recovering that energized mood, right?

34:17 Most people, as they drink more and more,

34:19 will now start to feel more and more suppressed.

34:23 The forebrain is now shutting down quite a lot,

34:25 a lot of the motor cortical areas that control

34:28 coordinated movement and deliberate movement start to shut down,

34:31 so people start to slur their speech, people start to shuffle their feet,

34:34 people forget their posture, people start to lean on things,

34:38 people start passing out on couches.

34:40 There's a great depression, not depression of the psychiatric depression sort,

34:45 but a depression of alertness and arousal, and eventually people will pass out.

34:53 Now, I said most people because there's a subset

34:55 of people that have gene variants or who are chronic drinkers

35:00 or who are chronic drinkers and have gene variants that, as they

35:04 ingest the third and fourth and fifth drink, what happens?

35:08 They become more alert, they start talking more, they feel great,

35:11 they have all sorts of ideas about the fun they could have that night.

35:14 And they're the ones that, if you've ever

35:16 fallen asleep at a party for whatever reason,

35:18 or you're getting tired and you're yawning,

35:19 you're looking around the room and, like,

35:21 these people are still drinking and partying and they're having

35:23 what seems to be this amazing time, often, not always,

35:27 those are the future alcoholics in the room,

35:31 or those are the people that have a genetic predisposition for alcoholism,

35:35 or those are the chronic drinkers,

35:36 the people who have built up enough of a tolerance or who have the chemical

35:41 genetic makeup such that increasing amounts of alcohol

35:45 make them feel better and better and better.

35:46 And of course, they, too, have a threshold beyond which their nervous system

35:50 will start to get diminished and they'll pass out,

35:53 fall over, et cetera, but that threshold is way,

35:57 way higher than it is for most people.

35:59 Now, this is important to understand, and it's important to understand because

36:03 I think everyone should know and recognize

36:06 their own predisposition and kind of risk in terms of developing alcoholism.

36:11 It's also important to understand because

36:13 it relates to the phenomenon of blackout.

36:15 Many people think that blacking out is passing out,

36:18 but blackout drunk is when people drink and they're talking and doing things,

36:22 sometimes, sadly or tragically,

36:25 they'll often drive home or walk home or they'll hop

36:28 on a bicycle and ride home or they'll go swimming in the ocean,

36:30 all, of course, very dangerous activities to do when people are really drunk,

36:34 or even a little bit drunk in some cases.

36:36 So these people will do these sorts of things and they do them because

36:40 they have the energy to do them and they feel good while doing them,

36:43 but they are doing them while the activity of neurons in the hippocampus,

36:47 which is involved in memory formation, are completely shut off.

36:50 And this is why the next day, you tell them,

36:54 "Hey, maybe we should talk about what happened last night." Like,

36:56 "What happened last night?" You said, "Well,

36:57 do you remember going to the party?" "Yeah, I know, it was great.

36:59 We did this, we did this." "And then what?" And it's very clear all of a sudden

37:04 that they have no recollection of all

37:06 the things they were doing despite being awake.

37:09 Now, I wish I could tell you that there's some sort

37:10 of blood test or other biomarker or even a fingerprint test that would

37:14 allow you to determine whether or not you have a propensity

37:17 to be one of these drinkers that has a predisposition for alcoholism.

37:22 And if you've ever been blackout drunk,

37:24 and certainly if you've been blackout drunk more than a few times,

37:27 you should be quite concerned.

37:29 And as we talk more about the more chronic effects and long-lasting

37:33 effects of alcohol consumption a little bit later in the episode,

37:36 I think it'll become clear as to why you should be concerned.

37:39 But in any case, there is something that can tell you whether

37:43 or not you might be in that category versus likely not in that category,

37:48 and I alluded to this a couple of times already,

37:49 but I want to be really clear that when people drink,

37:54 no matter who you are, initially,

37:56 there's that shutting down of those prefrontal cortical circuits,

37:59 there's a gradual shutting down of the circuits that control memory,

38:02 but then people divide into these two bins.

38:04 And these two bins are the people who,

38:07 after more than a couple of drinks, start to feel sedated,

38:11 and the people who, after more than a few drinks, do not start to feel sedated.

38:15 Now, of course there's going to be

38:17 differences created by how quickly people are drinking,

38:20 whether or not they're combining different types of alcohol,

38:23 the types of alcohol, et cetera, but in general,

38:25 that can predict whether or not you're somebody

38:27 who has a predisposition for alcoholism or not.

38:31 One also very interesting finding is that alcohol changes the relationship

38:36 between what's called the hypothalamus and the pituitary gland and the adrenals.

38:41 Now, the hypothalamus is a small collection of neurons about the size

38:44 of a large gumball that sits above the roof of your mouth,

38:47 and it houses neurons that are responsible for some

38:49 incredible aspects of our behavior and our mindset,

38:53 things like rage, things like sex drive, things like temperature regulation,

38:58 very primitive functions, including appetite, thirst, et cetera.

39:02 Alcohol, because it can go anywhere in the brain,

39:04 remember it's water- and fat-soluble, has effects on the hypothalamus.

39:09 The hypothalamus normally provides very specific

39:13 signals to what's called the pituitary gland.

39:15 This is a little gland that actually sticks out of the brain,

39:18 but it receives instructions from the hypothalamus.

39:22 And then the pituitary releases hormones into the bloodstream

39:25 that go and talk to your adrenals,

39:26 and your adrenal gland sit right above your kidneys in your lower back.

39:30 And the adrenals release, as the name suggests, adrenaline,

39:34 also called epinephrine, and also a molecule called cortisol,

39:37 which is involved in the kind of longer-term

39:40 stress response and it has some healthy effects, too, on the immune system.

39:42 Okay, so the hypothalamic-pituitary-adrenal axis, I know that's a mouthful,

39:47 you don't need to remember the names,

39:49 but the hypothalamic-pituitary-adrenal axis maintains

39:52 your physiological balance of what

39:54 you perceive as stressful and what you don't perceive as stressful.

39:58 People who drink regularly, so this, again,

40:00 could be just one or two drinks per night or it could be somebody

40:04 that drinks just on Fridays or just on Saturdays or maybe just on the weekend,

40:07 two to four drinks, well,

40:09 those people experience changes in their hypothalamic-pituitary-adrenal

40:13 axis that result in more cortisol, more of this so-called stress hormone,

40:17 being released at baseline, when they are not drinking.

40:21 This is really important.

40:23 People who drink a bit, and when I say a bit,

40:26 I don't mean one or two sips or even a glass of wine every once in a while.

40:29 I mean, again, people that are maybe having one drink

40:32 a night with dinner and maybe on the weekend a few more.

40:36 Again, I offer a bunch of different patterns to explain how it could

40:40 also be two or three drinks on Friday or six drinks only on Saturday.

40:44 Well, all of those groups experience increases in cortisol

40:48 release from their adrenal glands when they are not drinking,

40:52 and as a consequence,

40:54 they feel more stressed and more anxiety when they aren't drinking.

40:59 This is a seldom talked about effect of alcohol because

41:03 so often we hear about the immediate effects of alcohol, right?

41:06 And we've been talking about some of those effects,

41:08 effects like reducing the amount of stress.

41:10 I mean, how many times have we heard somebody say, "Ugh,

41:12 I need a drink." And then they have a drink and they're, like, calmed down,

41:15 now they can shake off the thoughts about the day's work they can

41:19 start to think about things in a maybe more grounded or rational way,

41:22 or at least they believe that, or they can somehow just relax themselves.

41:26 Well, while that very well may be true, that it can relax them,

41:30 when they are not drinking,

41:32 that level of cortisol that's released at baseline has increased substantially.

41:37 Again, this relates to a defined neural circuit between brain and body,

41:41 and it has to do with the ratio of cortisol

41:44 to some of the other hormones involved in the stress response.

41:48 We'll provide a reference to the study that describes how all

41:50 of this works for those of you that really want to delve into it,

41:53 but let's go back to this issue of those who

41:56 are prone to alcoholism versus those who are not.

41:59 Remember, there are people who have genetic variants,

42:02 meaning genes that they inherited from their parents,

42:05 that make it more likely that they will become alcoholics.

42:08 But there are also people who drink often who start to experience

42:13 this increase in alertness the longer they drink across the night.

42:17 Part of that effect, we think,

42:19 is because of changes in this hypothalamic-pituitary-adrenal axis.

42:23 So alcohol is kind of a double hit in this sense.

42:27 It's causing changes in our brain circuitry and neurochemistry

42:30 that, at the time in which we're inebriated, are detrimental,

42:34 and it's causing changes in neural circuitry that persist long past

42:38 the time in which we're experiencing the feeling of being tipsy or drunk.

42:42 Now, again, I don't want to demonize alcohol.

42:45 I'm not saying, oh, you know, if you have a glass of wine now and again

42:47 or you drink a beer now and again or even have,

42:49 you know, a mixed drink now and again

42:53 or a shot that that's necessarily terrible for you.

42:55 I certainly do not want that to be the message.

42:59 What I'm saying is that if people are ingesting alcohol chronically,

43:03 even if it's not every night,

43:05 there are well-recognized changes in neural circuits,

43:10 there are well-recognized changes in neurochemistry within the brain,

43:13 and there are well-recognized changes in the brain-to-body

43:18 stress system that generally point in three directions,

43:24 increased stress when people are not drinking,

43:27 diminished mood and feelings of well-being when people are not drinking,

43:32 and, as you'll soon learn,

43:34 changes in the neural circuitry that cause people to want to drink

43:40 even more in order to get just back to baseline or the place

43:44 that they were in terms of their stress modulation and in terms

43:47 of their feelings of mood before they ever started drinking in the first place.

43:51 So again, I don't want to demonize alcohol,

43:54 but I do want to emphasize that there are long-term plastic changes,

43:58 meaning changes in neural circuitry and hormone circuitry,

44:01 that, across a period of several months and certainly across

44:04 a period of years of the sorts of drinking patterns I described,

44:07 which I think, for most people, are going to sound, like, pretty typical, right?

44:11 I mean, nothing that I described so far was about drinking a case a night

44:14 or about binging on alcohol in the way that we often hear about it in the news.

44:18 These are pretty common patterns of alcohol consumption.

44:21 I mean, all you have to do is board a transatlantic flight or actually go

44:25 to an airport on a Sunday afternoon in a sunny area of the US and, you know,

44:29 people are having three, four, five, six beers, et cetera.

44:32 Again, personal choice is personal choice.

44:34 I'm not telling you what to do.

44:36 But it's very clear that those sorts of drinking

44:38 patterns are changing neural circuitry and they're changing hormone circuitry,

44:42 and I'd love to be able to tell you that they're changing them for the better,

44:44 but they simply are not.

44:46 They're actually changing them for the worse,

44:47 and worse is defined as making people less resilient to stress,

44:50 higher levels of baseline stress, and lower mood overall.

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46:07 Now, I've been talking a little bit about genetic predisposition,

46:10 but there are a couple of important points I'd like to make about that.

46:13 First of all, what sorts of genes are involved

46:16 in setting someone down the path of alcoholism or not?

46:20 Well, it should come as no surprise

46:22 that the genes that chronic alcohol usage modifies,

46:27 they tend to fall primarily in the pathways

46:30 related to genetic control over serotonin receptors,

46:35 GABA receptors, remember that top-down inhibition and the involvement of GABA,

46:39 and, no surprise, the HPA, the hypothalamic-pituitary-adrenal axis.

46:43 All of those, of course combined with environment,

46:46 they combine with patterns of abuse, right,

46:48 we know that if you're in a social setting where a lot of people are drinking,

46:51 the likelihood that you're going to drink is much higher,

46:54 social pressures, trauma, right?

46:57 Some people will use alcohol to self-medicate to try and turn

47:00 off their thinking or to deal with trauma, et cetera.

47:03 So they combine with the environment, but the genes that are

47:07 in the serotonin synthesis and receptor synthesis pathway,

47:10 GABA and HPA axis, combine with environmental

47:14 pressures to give rise to alcohol use disorders.

47:18 So there's a fairly coherent picture that we have here, right?

47:21 This is not a case where, for instance,

47:24 people that have a lot of the enzyme for metabolizing alcohol,

47:27 which we'll talk about in a minute, alcohol dehydrogenase,

47:30 it's not like they are necessarily the people that become alcoholics,

47:33 whereas certainly in certain cultures, certain Asian cultures in particular,

47:37 there are gene differences that lead them

47:40 to have low levels of alcohol dehydrogenase.

47:42 There are actually people who have so

47:44 little alcohol dehydrogenase that when they ingest alcohol,

47:46 they get very red and they just feel sick.

47:48 So if you're somebody that has a sip of alcohol and you just feel horrible,

47:51 it makes you feel nauseous, chances are you have gene variants that create

47:55 a situation where you're not making very much alcohol dehydrogenase.

47:59 You just simply can't metabolize alcohol so you just

48:01 get a rapid buildup of the toxic effects of alcohol,

48:04 the acetaldehyde, you're not converting it into those empty calories.

48:08 But in cultures where you have a lot of genetic variants

48:12 and genes expressed in people where they have a lot of alcohol dehydrogenase,

48:16 sure, they can drink more, and they're converting more of that alcohol

48:20 from its toxic form to a non-toxic form, and, yes, of course,

48:24 you will observe more alcoholism

48:26 in those communities because they're drinking more,

48:28 but I do want to emphasize that the environmental

48:31 factors are playing a strong role there,

48:32 too, because if you can drink more, you're likely to drink more.

48:35 If you're somebody that feels sick immediately from drinking,

48:37 it's likely that you're not going to engage in alcohol consumption,

48:40 especially if these things are genetically related, and, of course,

48:43 genes and culture and location in the world tend to run together.

48:47 So do you have the gene for alcoholism?

48:50 Well, there isn't one single gene.

48:53 Chances are if you have an immediate relative who's a chronic

48:57 abuser of alcohol or several relatives who are chronic abusers of alcohol,

49:01 well, that's going to predispose you to be an alcoholic.

49:05 But since you don't know which genes you express unless you do genetic testing,

49:08 and those things are available but most people aren't doing that, this assay,

49:12 if you will, and it's not an assay,

49:14 as we say, an assay is a test that you run in the lab to determine something,

49:19 and it's not one that I recommend that you go drink in order to do,

49:22 but if you've noticed that you or somebody else is somebody who can drink a lot

49:26 throughout the night and have increased energy

49:27 and can just drink and drink and drink,

49:29 and especially if there's blackout episodes,

49:32 not remembering things the next day despite being

49:34 alert throughout the entire night and so on, well,

49:36 then I would be very concerned that you might

49:39 actually have a genetic variant predisposing you to alcoholism.

49:42 The other thing that predisposes people to abuse of alcohol is age.

49:47 People who start drinking at younger ages are greatly predisposed

49:53 to developing alcohol dependence regardless

49:56 of your family history of alcoholism.

49:58 Okay, so I'm going to repeat that.

49:59 People who start drinking younger are at great risk for developing

50:04 alcoholism even if they don't have alcoholism in their family.

50:06 Now, of course, you don't have to be an epidemiologist to understand

50:10 that if you grow up in a family of drinkers and alcohol is everywhere,

50:13 and especially if there's peer pressure or lack of oversight,

50:16 then there's going to be a higher tendency,

50:19 or a higher probability, I should say,

50:21 that you will start drinking at a younger age.

50:23 However, even people that grow up nowhere near their relatives,

50:27 if they start drinking at a young age, so for instance,

50:30 at 13 or younger or 14 or 15, there's a much higher probability that they're

50:35 going to develop a long-lasting dependence on alcohol.

50:38 People who take their first sip of alcohol later,

50:42 15, 16, or one would hope even later,

50:44 I can say one would hope 'cause I'm now of that, you know,

50:47 age and generation where, you know,

50:48 you think about all the things that young people do, and you go, "Oh, gosh,

50:52 if they only would wait or if they only would abstain." You know?

50:55 It's just what happens.

50:56 I don't know, there's some neural circuit for that that I can't explain yet.

50:58 But people who, for instance, drink only once they reach legal age of drinking,

51:03 which in the US, I believe in every state is 21 years old,

51:06 if they take their first drink at 21,

51:08 the probability that they'll go on to develop

51:10 full-blown alcohol dependence or alcohol use disorder,

51:13 as it's called, AUD, is very low.

51:15 Now, a subset of them will because

51:17 they have such a strong genetic predisposition

51:19 or maybe life circumstances create a pattern

51:22 in which they become a chronic drinker.

51:24 But I found this very interesting.

51:26 Genes matter, but also the age in which somebody starts drinking really matters.

51:32 Now, whether or not that's because there

51:33 are changes in neural circuitry as a consequence

51:36 of that drinking that make people want to seek out more and more alcohol,

51:40 or whether or not there's some other effect,

51:42 maybe it's a change in hormones, et cetera,

51:44 that predisposes those young drinkers to become

51:47 chronic drinkers or even full-blown alcoholics,

51:49 certainly developing alcohol use disorder.

51:51 There's a definition for that.

51:52 We can talk about it.

51:53 It involves the amount of drinking over a certain period of time, et cetera.

51:57 So it's very clear that drinking early in life creates

52:00 a propensity for the development of alcohol use disorder later in life.

52:06 And while there is a genetic component to developing alcohol use disorder,

52:11 I find it very interesting that if people who

52:14 have those gene variants delay their onset of drinking,

52:18 well, then the probability that they'll develop

52:20 full-blown alcohol use disorder drops as well.

52:23 So again, it's genes and environments.

52:24 It's not an either/or and there's no single gene for alcoholism.

52:28 Well, I promise you I will also talk

52:29 about some of the documented positive effects of alcohol.

52:33 Although they are very few and far between, they do exist.

52:37 But before I do that, I would be remiss if I didn't emphasize some

52:41 more of the terrible things that alcohol does and the way that it does it.

52:45 And for those of you that enjoy alcohol, again,

52:48 I'd like to say I feel guilty about telling you this because I

52:53 know how much some people enjoy a good drink every once in a while,

52:55 and I say a good drink because some people do like the taste of alcohol.

52:59 I suppose I lucked out in that I don't really like

53:01 the taste of alcohol and that it just puts me to sleep,

53:03 but I know that people do enjoy it.

53:04 And I do want to point out that there is zero evidence that, you know,

53:11 provided somebody is of drinking age,

53:14 certainly not in the stage of brain development,

53:17 that having one drink or two drinks every now and again,

53:20 meaning every three or four weeks or once a month,

53:23 that is not going to cause major health

53:27 concerns or major health issues for most people.

53:30 I suppose if you have zero or very little alcohol dehydrogenase,

53:34 it might make you feel sick, but then you're probably not the kind

53:36 of person that's going to be drinking at all.

53:38 So, again, if you enjoy alcoholic drinks,

53:41 I'm not trying to take them away from you by any means,

53:46 but you should know what drinking does if you're

53:48 consuming it in this kind of typical chronic pattern, as we can now refer to it,

53:52 which is that one or two a night or a few

53:56 stacked up on Friday and maybe three or four on Saturday,

54:00 this kind of pattern of drinking, which is quite common.

54:03 And one of the more serious effects that we should

54:05 think about is the impact on the so-called gut-brain axis,

54:08 or for sake of today's discussion, the gut-liver-brain axis.

54:12 I don't think the gut-liver-brain axis has ever

54:14 been discussed on this podcast, maybe any podcast.

54:16 Although at the moment I say that, you know, the gut-liver-brain axis,

54:20 people are going to come after me with, I suppose, gut, liver, and brains.

54:24 In any event, you have a brain.

54:27 You have a gut.

54:29 That gut runs from your throat down to the end of your intestine.

54:36 Your gut and your brain communicate by way of nerve cells,

54:39 neurons and nerve connections, the vagus nerve in particular,

54:43 and by way of chemical signaling.

54:45 Your gut also communicates by way of chemical signaling and, believe it or not,

54:49 by way of neural signaling, too, to your liver.

54:52 And, as we talked about earlier, the liver is the first site in which alcohol

54:56 is broken down or metabolized into its component parts.

55:01 The liver is also communicating with the brain

55:04 through chemical signaling and neural signaling,

55:06 so we have the gut-liver-brain axis.

55:10 And what you find is that people who ingest alcohol

55:15 at any amount are inducing a disruption in the so-called gut microbiome,

55:21 the trillions of little microbacteria that take

55:24 resident in your gut and that live inside you all the time and that help

55:27 support your immune system and that literally

55:29 signal by way of electrical signals

55:31 and chemical signals to your brain to increase

55:34 the release of things like serotonin and dopamine

55:37 and regulate your mood generally in positive ways.

55:39 Well, alcohol really disrupts those bacteria,

55:42 and this should come as no surprise.

55:43 I mean, earlier, we talked about this and it's well known,

55:45 if you want to, you know,

55:46 sterilize something, you want to kill the bacteria, you pour alcohol on it.

55:49 And I can remember scraping myself or cutting myself

55:53 or I was always injuring myself when I was a kid,

55:55 and, you know, the moment they take out the peroxide, you're like, "Oh, boy,

55:59 here it comes." But if there's no peroxide around and you've

56:01 got a wound there and you need to clean it out,

56:03 yeah, they'll use alcohol, which I do not recommend, by the way.

56:06 That's one of the harshest ways to clean a wound.

56:08 But for centuries, thousands of years really,

56:11 alcohol has been used in order to clean things and kill bacteria.

56:15 So alcohol kills bacteria and it is

56:19 indiscriminate with respect to which bacteria it kills,

56:22 so when we ingest alcohol and it goes into our gut,

56:24 it kills a lot of the healthy gut microbiota.

56:27 At the same time, the metabolism of alcohol in the liver,

56:30 which you now understand, that pathway involving NAD, acetaldehyde, and acetate,

56:37 that pathway is proinflammatory,

56:40 so it's increasing the release of inflammatory cytokines,

56:43 things like IL-6, et cetera, tumor necrosis factor alpha.

56:47 If you'd like to learn more about the immune system,

56:49 we did an episode all about the immune system.

56:51 You can find it at hubermanlab.com.

56:52 It'll teach you all the basics of what are cytokines,

56:55 what are mast cells, et cetera.

56:57 In any event, all these proinflammatory molecules, those are being released.

57:03 You've now got disruption of the gut microbiota.

57:07 As a consequence, the lining of the gut is disrupted,

57:10 and you develop, at least transiently, leaky gut.

57:15 That is, bacteria that exists in the gut which are bad

57:18 bacteria can now pass out of the gut into the bloodstream,

57:20 so you've got a two-hit kind of model here.

57:23 In biology, we talk about two-hit models, that is,

57:25 it's kind of a one plus one equals four,

57:27 and it's generally when you hear two-hit, it's not a good thing.

57:30 So you've got bad bacteria from partially

57:33 broken down food moving out of the gut,

57:36 the good bacteria in the gut have been killed.

57:38 You might say, why doesn't the alcohol kill the bad bacteria in the gut?

57:42 Well, the bad bacteria that are from partially digested food

57:47 oftentimes escape the gut before the alcohol can disrupt them,

57:52 and so now you've got leaks in the gut wall,

57:55 you've got the release of this bad bacteria,

57:57 you've got inflammatory cytokines and other

57:59 things being released from the liver, and they are able to get

58:02 into the brain through what's called a neuroimmune signaling.

58:06 And what's really bizarre, in terms of the way that this manifests in the brain,

58:10 I mean, it's not the way I would've done it,

58:12 but then again, as I always say, I wasn't consulted at the design phase,

58:16 and anyone who says they did, you should be very skeptical of them.

58:20 The net effect of this is actually to disrupt

58:23 the neural circuits that control regulation of alcohol intake,

58:27 and the net effect of that is increased alcohol consumption.

58:32 So this is just terrible, right?

58:33 I mean, so you take in something that disrupts two systems,

58:37 the gut microbiota, and it disrupts in two ways,

58:39 it's killing the good gut microbiota and it's allowing

58:43 the bad bacteria to move from the gut into the bloodstream,

58:47 you've also got proinflammatory cytokines coming from the liver,

58:50 and those converge or arrive in the brain and create

58:55 a system in which the neural circuits cause more drinking.

59:00 That's a bad situation.

59:01 And this is why people who drink regularly,

59:04 even if it's not a ton of alcohol, again,

59:07 of the sorts of patterns of drinking I talked about before,

59:09 and certainly for those that are chronic heavy drinkers,

59:12 what you end up with is a situation in which

59:14 you have inflammation in multiple places in the brain

59:17 and body and the desire to drink even more

59:20 and to further exacerbate that inflammation and the gut leakiness.

59:24 So this is basically a terrible scenario for the gut-liver-brain axis,

59:28 and it's especially prevalent in so-called alcohol use disorder,

59:31 again, people that are ingesting somewhere between 12 and 24 drinks per week.

59:34 For those of you that are interested in learning

59:36 more about the gut-liver-brain axis and, in particular,

59:39 alcohol use disorder, I'll provide a link in the show note captions.

59:42 There's a wonderful review on this that details that.

59:45 But on the positive side, it points to the possibility that at least some,

59:50 again, at least some, of the negative effects of alcohol consumption,

59:53 whether or not you're somebody who's currently

59:55 ingesting alcohol or who used to ingest

59:57 alcohol and is trying to so-called repair these systems of the brain and body,

1:00:01 whether or not replenishing the gut microbiota is going to be beneficial.

1:00:04 And we know that there are ways to do that, and we know

1:00:07 that there's at least some promise

1:00:09 for the ability for this system to repair itself.

1:00:11 How does one do that?

1:00:13 Well, I've talked before about this on the podcast,

1:00:15 but studies done by colleagues of mine at Stanford, Justin Sonnenburg,

1:00:18 who's been on this podcast as a guest,

1:00:20 an amazing episode all about the gut microbiome, and his collaborator,

1:00:23 Chris Gardner, also at Stanford School of Medicine,

1:00:25 have explored not alcoholism, but what are ways to improve the gut microbiota,

1:00:32 in particular, to reduce the production of inflammatory

1:00:37 cytokines and to adjust what's called the inflammatome.

1:00:40 You've heard of the genome and the proteome, et cetera.

1:00:43 Well, the inflammatome is the total array or at least

1:00:47 the near-total array of genes and proteins that control inflammation.

1:00:51 How can you reduce inflammation and make that inflammatome healthier?

1:00:55 Well, they've shown that two to four servings of fermented foods per day,

1:00:59 and here, I'm not referring to fermented alcohol.

1:01:01 I'm talking about low-sugar fermented foods, so things like kimchi,

1:01:05 sauerkraut, natto, for those of you that like Japanese food.

1:01:09 There are others, I know,

1:01:11 things like kefir or things like yogurts that have a lot of active bacteria,

1:01:15 again, low-sugar varieties of all these things.

1:01:19 Those are terrific at reducing inflammatory

1:01:22 markers and at improving the gut microbiome.

1:01:25 One could imagine that either inoculating oneself

1:01:29 from some of the effects of alcohol,

1:01:30 although I'd prefer that people just not drink alcohol chronically, frankly,

1:01:34 or if somebody's trying to repair their gut microbiome

1:01:37 because they ingested a lot of alcohol or because

1:01:39 they had a lot of these inflammatory cytokines

1:01:41 for many years or even a short period of time,

1:01:44 regular ingestion of two to four servings

1:01:46 of these fermented foods can be quite beneficial.

1:01:51 I want to make it clear,

1:01:52 that has not been examined specifically in the context of alcohol use disorder,

1:01:57 but because a huge component of the negative effects of alcohol use disorder are

1:02:02 based in this gut-liver-brain axis and disruption

1:02:04 of the gut microbiome and the inflammatory cytokines,

1:02:07 it stands to reason that things

1:02:09 that are well-established to improve inflammation status,

1:02:12 in other words, reduce inflammation,

1:02:14 such as ingesting two to four servings of low-sugar fermented foods per day,

1:02:19 makes sense in terms of trying to repair or replenish the system.

1:02:23 One could also imagine taking probiotics or prebiotics.

1:02:25 Certainly that would work as well, although I've sort of favored

1:02:29 the discussion around fermented foods and replenishment

1:02:31 of the gut microbiome mostly because there are more studies that have

1:02:36 examined that in humans and because of the direct relationship that's

1:02:39 been established between doing that and reducing

1:02:42 negative markers within the inflammatome.

1:02:44 And I should mention, along the lines of repair and recovery,

1:02:47 I put out a question on Twitter the other day.

1:02:49 I said, "What do you want to know about alcohol?" I got more than 1,000

1:02:52 questions and I'll take some more

1:02:54 of those questions a little later in the episode.

1:02:55 But one of the things I noticed is

1:02:56 that many of the questions, hundreds, in fact,

1:03:00 related to the question of, well, if I drank a lot previously, am I doomed?

1:03:05 Can I reverse the negative effects?

1:03:07 Or, you know, I'm trying to drink less and I'm

1:03:10 trying to improve my health as I do that.

1:03:11 What should I do?

1:03:12 Well, certainly focusing a bit on the gut microbiome ought to be useful.

1:03:17 The other thing I should mention is as people wean themselves off alcohol,

1:03:21 even if they're not full-blown alcoholics or have alcohol use disorder,

1:03:25 they should understand that that increase

1:03:27 in cortisol that we talked about earlier

1:03:29 that leads to lower stress threshold and greater feelings of anxiety and stress,

1:03:35 that's going to be present and it's going to take some time to dissipate.

1:03:39 So for some people, it might even just be helpful to realize that as you

1:03:43 try and wean yourself off alcohol or maybe you even go cold turkey,

1:03:47 that increased anxiety and feelings of stress should be expected.

1:03:52 And in that case, I would point you to an episode that we did on master stress.

1:03:55 You can find that, again, at hubermanlab.com.

1:03:57 It's got a ton of behavioral,

1:03:59 nutritional, supplementation-based, exercise-based,

1:04:01 I suppose, exercise is behavioral, but a lot of tools.

1:04:04 You can navigate to those easily 'cause we have timestamps

1:04:06 so you can go right to the topic of interest.

1:04:08 Those tools are going to be very useful

1:04:09 in trying to clamp or control your stress.

1:04:12 And the point here is just that some increase in stress should be expected,

1:04:17 and it should be expected because of that increase in cortisol

1:04:19 that occurs with even low-level consumption yet chronic alcohol consumption.

1:04:24 Now I'd like to talk about a fairly common phenomenon,

1:04:27 which is post-alcohol consumption malaise, also referred to as hangover.

1:04:34 Hangover is a constellation of effects ranging

1:04:37 from headache to nausea to what's sometimes called hangxiety,

1:04:42 which is anxiety that follows a day of drinking.

1:04:47 Hangxiety, I think we can understand physiologically

1:04:50 if we think about that process of alcohol

1:04:54 intake increasing the amount of cortisol and the ratio

1:04:58 of cortisol to some other stress hormones.

1:05:00 That well explains why some people wake up the day after or even the day the day

1:05:06 after a night drinking and feel anxious and not

1:05:10 well and stressed for reasons they don't understand.

1:05:13 So if you're somebody who experiences hangxiety, then, again,

1:05:17 I refer you to the master stress episode that we put out some time ago,

1:05:22 and you can find that at hubermanlab.com, tools to deal with anxiety,

1:05:25 tools to deal with stress, ranging, again,

1:05:27 from behavioral to nutritional and supplement-based, et cetera.

1:05:30 That, of course, is not justification for going out

1:05:33 and drinking so much that you get hangxiety-induced hangover,

1:05:38 but for those of you that are experiencing post-alcohol consumption hangxiety,

1:05:41 as it were, that could be a useful resource because

1:05:45 I certainly don't want anyone experiencing uncomfortable amounts of anxiety,

1:05:49 and there are great tools and resources for that.

1:05:51 Now, the other aspects of hangover,

1:05:54 such as the stomachache or headache or feelings of malaise or fogginess,

1:06:01 those could be related to a number of different things

1:06:02 and probably are related to a number of different things.

1:06:05 First of all, the sleep that one gets after even just one, yes,

1:06:10 even just one glass of wine or a beer is not the same

1:06:14 sleep that you get when you don't have alcohol circulating in your system.

1:06:18 And not trying to be a downer here,

1:06:19 but this was discussed in the Huberman Lab Podcast episode where I had Dr.

1:06:24 Matthew Walker from UC Berkeley on.

1:06:26 And, of course, Dr.

1:06:27 Walker is a world expert in sleep,

1:06:29 runs one of the preeminent laboratories studying sleep and its effects,

1:06:33 wrote the incredible book, "Why We Sleep," and so on.

1:06:37 Dr.

1:06:37 Walker told me, and it certainly is supported by lots

1:06:41 and lots of quality peer-reviewed studies in animals and in humans,

1:06:45 that when alcohol is present in the brain

1:06:47 and bloodstream that the architecture of sleep is disrupted.

1:06:50 Slow-wave sleep, deep sleep, and rapid eye movement sleep,

1:06:53 all of which are essential for getting

1:06:54 a restorative night's sleep, are all disrupted.

1:06:56 So for those of you that are drinking a glass or two of wine

1:06:59 or having a hard liquor drink or a beer in order to fall asleep,

1:07:05 the sleep you're getting is simply not high-quality sleep,

1:07:07 or certainly not as high-quality as the sleep you'd be

1:07:10 getting if you did not have alcohol in your system,

1:07:12 Of course, when we're talking about hangover,

1:07:14 we're talking generally about the consumption

1:07:17 of more than just one or two drinks.

1:07:19 Of course, for some people,

1:07:20 one or two drinks is probably sufficient to induce hangover,

1:07:23 but for most people it's going to be having three or four,

1:07:25 exceeding their typical limit, as it's called.

1:07:28 Again, not the legal limit, that's a whole other business.

1:07:31 But when one ingests too much alcohol for them,

1:07:36 one of the reasons they feel terrible the next

1:07:39 day is because their sleep isn't really good sleep.

1:07:41 In fact, it's not even sleep.

1:07:42 It's often considered pseudosleep,

1:07:44 or at least that's what it's called in the sleep science field,

1:07:47 because people are in kind of a low-level,

1:07:49 hypnotic kind of trance, it's not real sleep,

1:07:51 there are multiple bouts of waking up,

1:07:52 they may not even realize they're waking up multiple times.

1:07:55 Okay, so there's the sleep-induced effects.

1:07:57 Then there are the disrupted gut microbiome effects,

1:08:01 some of which we talked about earlier so

1:08:03 now you understand the mechanism of alcohol destroying good,

1:08:07 healthy gut microbiota, which then leads to leaky gut and things of that sort.

1:08:12 But one could imagine, again, could imagine,

1:08:15 and there is some evidence starting to support this, that, again,

1:08:19 ingesting low-sugar fermented foods or maybe

1:08:22 even prebiotic or probiotics to support the gut microbiome might assist in some

1:08:26 of the gut-related malaise associated with hangover.

1:08:30 In other words, get those gut microbiota healthy again as quickly as possible,

1:08:34 or maybe even before you drink, have those gut microbiota healthy.

1:08:37 I would hope that you'd do that.

1:08:38 I think everybody should be doing something to support their gut microbiome,

1:08:40 whether or not it's the ingestion of low-sugar fermented foods daily

1:08:43 or at least on a regular basis or ingestion of probiotic or prebiotic.

1:08:47 The gut microbiome is so important for so many different things.

1:08:51 In terms of hangover and headache,

1:08:55 we know that that's caused by vasoconstriction,

1:08:58 the constriction of blood vessels that tends to occur

1:09:00 as a rebound after a night of drinking.

1:09:02 Alcohol can act as a vasodilator, it can dilate the blood vessels.

1:09:06 Part of that is associated with the increase in so-called parasympathetic tone.

1:09:11 We have an autonomic nervous system and it's got a sympathetic component.

1:09:14 These are neurons that make us more alert,

1:09:17 and if they're very active, they make us very stressed.

1:09:19 There's also the parasympathetic aspect of the autonomic nervous system.

1:09:23 This is all just fancy geek speak for the parts of your brain and body,

1:09:26 the nerve cells that make you very relaxed.

1:09:28 When you're very relaxed, there tends to be vasodilation.

1:09:32 It allows for more movement of blood and other things through the bloodstream,

1:09:37 and alcohol tends to induce some vasodilation,

1:09:40 at least in some of the capillary beds.

1:09:42 And then when the alcohol wears off,

1:09:44 there's vasoconstriction and people get brutal headaches.

1:09:48 That's why some people will take aspirin or Tylenol

1:09:51 or Advil or things like that, the sort of non-steroid anti-inflammatories.

1:09:55 I should mention, there is a lot of literature coming out that some

1:09:59 of these non-steroid anti-inflammatory drugs are not good

1:10:02 for us for a number of different reasons,

1:10:04 the way they impact the liver, the way they impact the immune system,

1:10:08 and, no surprise, the way they impact the gut microbiome.

1:10:11 So I'm not one to tell you what medications to take or not take,

1:10:15 but you certainly would want to do a quick web search of effects of non-steroid

1:10:21 anti-inflammatories and aspirin before you start taking

1:10:24 those, or stop taking those, for that matter.

1:10:27 Generally, they will alleviate headache,

1:10:29 but they can often have other issues, including liver issues.

1:10:31 And keep in mind, the night after drinking,

1:10:33 your liver has already taken a beating because of the need

1:10:37 of the liver to convert alcohol from acetaldehyde into acetate,

1:10:42 which is now a pathway that you well understand.

1:10:45 So I'm not certain and, in fact, I believe it's not the greatest idea to burden

1:10:49 your liver further through the use of things that are going

1:10:52 to cause it to have to work harder and metabolize

1:10:55 things if the goal is simply to alleviate a headache.

1:10:58 There's a lot of kind of lore, old school lore about how to relieve a hangover.

1:11:03 We already talked about how eating food won't do that but eating

1:11:06 food will prevent the rapid absorption

1:11:09 of even more alcohol into the bloodstream.

1:11:11 There's the lore that one should simply ingest more alcohol.

1:11:15 What terrible advice that is.

1:11:17 That's just going to delay an even worse hangover.

1:11:19 However, I'd be remiss if I didn't say

1:11:22 that the reason that that myth came to be,

1:11:25 or that, I should say, that truth came to be,

1:11:28 because indeed ingesting more alcohol will alleviate a hangover

1:11:32 but then a worse hangover will show up,

1:11:34 the reason that came to be is because ingestion of more alcohol

1:11:37 will cause those constricted vessels that are

1:11:40 giving the headache to dilate again.

1:11:42 But, of course, ingesting more alcohol to relieve

1:11:43 a hangover is simply a bad idea.

1:11:45 Just don't do it.

1:11:46 I think this is called the hair of the dog approach.

1:11:48 Maybe someone can put in the show note captions

1:11:50 on YouTube why it's called the hair of the dog.

1:11:53 I can come up with a few ideas but they're not going to be very good ones,

1:11:58 and some of them would probably even be outright ridiculous.

1:12:02 So do not ingest more alcohol simply to try and recover from a hangover.

1:12:06 I know many people have tried that one before but that's a terrible idea.

1:12:10 Now, one thing that you'll also hear out there is that deliberate cold exposure,

1:12:14 for instance, taking a cold shower, might relieve hangover.

1:12:17 I find this one particularly interesting because we've

1:12:19 done episodes on the benefits of deliberate cold exposure.

1:12:21 We have an entire episode about that.

1:12:23 You can find it, again, hubermanlab.com.

1:12:25 There are direct links to some of the tools

1:12:28 related to deliberate cold exposure and we

1:12:30 have an entire newsletter on deliberate cold

1:12:33 exposure protocols that you can find on hubermanlab.com,

1:12:35 go to our Neural Network newsletter.

1:12:37 So those of you that are interested in ice baths and cold

1:12:40 showers and ways to leverage those, you can find that there.

1:12:43 What you won't find there is a description of how

1:12:45 to use deliberate cold exposure for sake of treating hangover.

1:12:48 But here, I went into the literature and I found something kind of interesting.

1:12:51 There is some evidence that increasing levels of epinephrine

1:12:54 in the bloodstream can actually help with alcohol clearance.

1:12:58 That was very surprising to me,

1:12:59 and I want to point out this is not a large and robust literature,

1:13:03 but there's some evidence pointing to the fact that when levels of epinephrine,

1:13:06 adrenaline, are raised in the brain and bloodstream,

1:13:08 that some of the components of alcohol metabolism can be accelerated

1:13:12 and some of the inebriating effects of alcohol can be reduced,

1:13:15 so maybe this old school lore of taking

1:13:17 a cold shower actually has something to it.

1:13:19 So in thinking about the use of deliberate cold exposure in order to reduce

1:13:23 the effects of hangover or to more

1:13:26 rapidly clear alcohol from the brain and bloodstream,

1:13:29 I want to be very clear and I want to emphasize your safety.

1:13:34 The way to do that is to understand

1:13:36 that alcohol lowers core body temperature, okay?

1:13:39 It can make people slightly hypothermic.

1:13:42 It's going to drop core body temperature.

1:13:45 So if you were inebriated and you went and got into a body of water, right,

1:13:50 a pool or a lake or something, first of all,

1:13:52 that's extremely dangerous to do while you're inebriated, right?

1:13:55 People drown all the time.

1:13:56 People drown, they die as a consequence of doing that, so please don't do that.

1:14:00 But also, if it's very cold water,

1:14:03 your core body temperature is going to drop even further.

1:14:05 Now, if you've heard the episodes

1:14:06 that I've done on deliberate cold exposure previously,

1:14:10 I've talked about how normally, when people are not ingesting alcohol,

1:14:14 they get into an ice bath or a cold shower

1:14:16 and their body temperature initially dips but then it rebounds and increases.

1:14:19 That's a process that's going to occur when

1:14:21 people do not have alcohol in their system.

1:14:23 When you have alcohol in your system,

1:14:25 one of the reasons that you become hypothermic is

1:14:27 because there's a disruption in those hypothalamic brain areas,

1:14:30 in particular, the brain area called the medial

1:14:32 preoptic area that regulates core body temperature.

1:14:35 So it's not so much that alcohol makes you cold,

1:14:38 it's that alcohol disrupts the central command

1:14:41 centers of the brain that control temperature regulation,

1:14:43 and that leads you to be slightly hypothermic.

1:14:46 So if you then go get into a very cold lake

1:14:49 or you get into even a cold shower or an ice bath,

1:14:52 there's the possibility of you going very, very far down the ladder into very

1:14:58 hypothermic territory and that can be very dangerous.

1:15:00 Now, in terms of dealing with hangover when

1:15:02 the alcohol has been largely cleared from your system, well,

1:15:05 that's where some of this old lore combines

1:15:08 with some of the modern science and says, well, if you can spike adrenaline,

1:15:13 and certainly getting into an ice bath or getting

1:15:15 into a cold shower or any kind of cold body of water,

1:15:19 provided you can do that safely,

1:15:20 that will sharply increase your adrenaline and, I should say, your dopamine.

1:15:24 That's been shown and we've talked about this on the podcast before.

1:15:26 You get these long, extended increases,

1:15:28 several hours of increases in dopamine from deliberate cold exposure.

1:15:31 It's well-documented in humans, by the way.

1:15:34 So one could imagine using deliberate cold exposure

1:15:37 as a way to accelerate the recovery from hangover.

1:15:41 Provided that's done safely,

1:15:43 I think there's no reason to not explore that, and if

1:15:46 you wonder what safely is and what temperatures to use,

1:15:49 please check out the episode on deliberate cold exposure.

1:15:52 Cold showers, therefore,

1:15:53 might actually be one way to at least partially relieve hangover.

1:15:57 Certainly the science from various places

1:16:00 in the literature converged to say that.

1:16:02 But, again, be careful, please, please,

1:16:04 please be careful not to get into cold water when you are inebriated.

1:16:09 It's absolutely dangerous for all the obvious reasons,

1:16:12 and it's dangerous also for the nonobvious reasons,

1:16:14 not the least of which is the dramatic decreases

1:16:17 in core body temperature that can make you dangerously hypothermic.

1:16:21 Now, how would you go about using

1:16:23 deliberate cold exposure to accelerate recovery from hangover?

1:16:25 Well, there, I would look to the kind of standard protocols of, you know,

1:16:28 one to three minutes or maybe even six minutes if you can tolerate it,

1:16:31 or if you're really cold-adapted,

1:16:33 maybe you do seven or ten minutes in a cold shower,

1:16:35 although that could be a lot.

1:16:36 Most people are going to experience

1:16:39 a sharp increase in epinephrine, in adrenaline,

1:16:41 and a long-lasting increase in dopamine from one

1:16:44 to three minutes of deliberate cold exposure,

1:16:47 ideally done immersion up to the neck,

1:16:49 again, do this safely, please, please, please,

1:16:51 or a cold shower where you're getting under the shower as much as possible.

1:16:54 How cold?

1:16:54 Well, that's going to vary person to person.

1:16:56 I suggest making it as cold as is uncomfortable such that you really

1:17:00 want to get out but that you know you can stay in safely without,

1:17:02 for instance, giving yourself a heart attack, because if the water is really,

1:17:05 really cold, of course you can give yourself a heart attack.

1:17:06 Most showers won't go that cold, although probably some will.

1:17:10 Again, please use caution.

1:17:11 Spike your adrenaline, spike your dopamine with deliberate cold exposure safely.

1:17:15 Other components of hangover that could be good

1:17:17 targets for trying to alleviate hangover, and, here,

1:17:20 I hope you are getting the picture because it

1:17:22 is accurate to say that hangover is a multifaceted phenomenon.

1:17:27 It's not like one molecule and one receptor.

1:17:29 It's a bunch of things happening in the brain and body.

1:17:31 But is the dehydration associated with alcohol?

1:17:34 Alcohol is a diuretic.

1:17:36 For multiple reasons,

1:17:37 it causes people to excrete not only water but also sodium.

1:17:41 Sodium is an electrolyte critical for the function of neurons,

1:17:44 so making sure that you have enough sodium,

1:17:46 potassium, and magnesium, so-called electrolytes,

1:17:49 is going to be important for proper brain function, bodily organ function.

1:17:54 Even for people that have just had one or two drinks the night before,

1:17:57 it's likely that your electrolyte balance

1:17:59 and your fluid balance is going to be disrupted,

1:18:02 and that's because alcohol also disrupts the so-called vasopressin pathway.

1:18:06 I talked a lot about vasopressin and the way

1:18:09 that it interacts with and controls different aspects

1:18:12 of water retention and water release from the body

1:18:15 in the form of urine in the episode on salt.

1:18:18 So, again, I'm referring to hubermanlab.com as the site where you can

1:18:22 find that episode on salt balance and ways to restore electrolyte balance.

1:18:26 Having your electrolytes at the proper levels before you drink is ideal.

1:18:31 Some people will say for every glass of alcohol that you drink,

1:18:35 you should drink one glass of water.

1:18:36 I would say better would be two glasses

1:18:39 of water given the dehydrating effects of alcohol,

1:18:42 and even better would be water with electrolytes.

1:18:44 That certainly would set you up for a better day the next day.

1:18:47 And if you don't manage to do that, 'cause I suppose it's kind of geeky

1:18:51 walking around with electrolyte packets out

1:18:53 at the bar or whatnot, although, you know, geeky, in my book, is a good thing,

1:18:59 the next day, you could take some electrolytes upon waking,

1:19:02 maybe even some before you go to sleep the night of drinking.

1:19:05 So hangover's made worse by disturbed sleep,

1:19:09 made worse by disrupted gut microbiome, made worse by disrupted electrolytes,

1:19:13 made worse by the depletion of epinephrine and dopamine.

1:19:16 That's why replenishing the microbiome with fermented foods,

1:19:19 low-sugar fermented foods, that is,

1:19:21 that's why using safe deliberate cold exposure

1:19:25 for spiking adrenaline and for increasing dopamine,

1:19:29 and that's why consuming electrolytes are all going to be beneficial.

1:19:34 The folks over at examine.com,

1:19:36 a website that I really like because it just has so much useful information,

1:19:41 have assembled a list of things that have been proposed,

1:19:46 purported to improve, or, I should say, to remove the effects of hangover,

1:19:51 and, as they point out and I would like to point out over there,

1:19:54 there isn't a lot of quality science to support

1:19:57 the idea that any one compound can eliminate hangover.

1:20:01 And that's probably because hangover, again,

1:20:02 arises from multiple organs and tissues and systems in both the brain and body.

1:20:07 Nonetheless, they have a terrific list over there of things,

1:20:10 everything from Japanese pear fruit juice has been proposed

1:20:14 to do this, to some other really esoteric things, even things like yohimbine.

1:20:20 Frankly, when I look at the literature there and elsewhere,

1:20:25 one simply cannot find the magic substance,

1:20:29 the one herb, the one potion that can wipe away hangover.

1:20:33 Getting rid of hangover is going to be best solved

1:20:37 by doing a collection of a small number of very powerful things,

1:20:41 of which I've already listed off a few.

1:20:44 However, there are some additional things

1:20:46 that one can do for relieving hangover, and one of them is to be very

1:20:51 thoughtful about what sorts of alcohol one consumes.

1:20:54 So I find this interesting.

1:20:56 There have actually been studies of which

1:20:58 types of alcohol lead to the greatest hangovers.

1:21:02 There's actually a lot of legend and lore about this as well.

1:21:06 Some people have said, for instance,

1:21:07 that drinks that have a high sugar content lead to greater hangovers.

1:21:12 Turns out that's not the case,

1:21:13 or at least that's not what the science points to.

1:21:15 If you look at the expected hangover severity,

1:21:18 what you find is that at the bottom end of the scale,

1:21:21 there's a drink that I'm not going to tell you, for the moment,

1:21:25 but what you find is that near it is, for instance, beer.

1:21:29 The consumption of beer, provided it is not overconsumption,

1:21:33 right, it's not far beyond the tolerance of the individual,

1:21:36 so it's one or two beers, is less likely to cause a hangover than, say, whiskey.

1:21:42 And a glass of whiskey, or, you know, not as much whiskey as beer, of course,

1:21:46 but a glass of whiskey, for instance,

1:21:48 is more likely to cause hangover than gin, as it turns out.

1:21:53 Again, this is what's fallen out of the data.

1:21:56 And yet a glass of rum or red wine is more likely

1:22:00 to cause a hangover than any of the other things I've mentioned so far.

1:22:04 At the top, top, top of the list of drinks that induce hangover is brandy.

1:22:09 And one could then say, "Well, doesn't brandy have a lot of sugar?

1:22:12 Maybe it's the sugar that's causing

1:22:14 hangovers." And this is something that's been, again, discussed over and over,

1:22:16 that people say, "Oh,

1:22:17 it's the high-sugar drinks that cause hangover." It turns out, however,

1:22:21 that when one looks at alcoholic drinks and sugar content and hangover,

1:22:26 at the very bottom of the list is,

1:22:30 gosh, this makes me cringe just to think about,

1:22:32 is ethanol diluted in orange juice.

1:22:35 Ugh, I can't believe people actually drink

1:22:37 this, but ethanol diluted in orange juice.

1:22:39 So this is not vodka and orange juice, okay?

1:22:41 Vodka was third on the list from the bottom of drinks that induce hangover.

1:22:45 Again, this is within amounts that are comfortable for the person to drink,

1:22:50 that they have enough experience with or that they have

1:22:52 the body weight to tolerate without getting very, very drunk.

1:22:55 So the point is that if it were sugar that's causing hangover, well,

1:23:00 then the ethanol diluted in orange juice would probably be

1:23:03 at the top of the list in terms of inducing hangover.

1:23:06 But it's not, it's at the bottom of the list,

1:23:07 and brandy is at the top of the list.

1:23:09 So what you find is that what scales from ethanol

1:23:13 diluted in orange juice to beer to vodka to gin,

1:23:16 here, I'm ascending the hierarchy of things that cause hangover,

1:23:19 gin, white wine, whiskey, rum, red wine, and then brandy at the peak,

1:23:24 it's sort of the world heavyweight champion of hangover-inducing drinks,

1:23:29 well, what's increasing are congeners within those drinks.

1:23:34 Congeners are things like nitrites and other

1:23:37 substances that give alcohol it's distinctive

1:23:41 flavor and that also lead to some of the inebriating effects of alcohol.

1:23:46 Now, then you ask, "Okay, well, what is it that these congeners are doing?

1:23:50 And what are these nitrites doing?" And guess what?

1:23:53 While they do have effects on the brain and on other tissues,

1:23:57 their main effects are to disrupt the gut microbiome.

1:24:00 So what this points to again is that having a healthy gut

1:24:05 microbiome and perhaps ensuring that you

1:24:08 bolster your gut microbiome the day after

1:24:12 drinking is going to be especially important

1:24:14 for warding off hangover or at least

1:24:17 reducing the effects of hangover or the symptoms of hangover or both.

1:24:21 I would love to see a study on this.

1:24:24 I could imagine designing the study myself,

1:24:26 although this isn't really the sorts of things my laboratory does,

1:24:29 but can imagine some people getting probiotic and prebiotic,

1:24:32 some regularly, some just after drinking, or low-sugar fermented foods,

1:24:37 and see what the effects are in terms

1:24:38 of subjective effects of hangover but also some physiological measures.

1:24:43 I think the way to think about hangover overall is that, again,

1:24:47 it represents a multifaceted, multi-organ,

1:24:51 multi-tissue phenomenon, and the best way to deal with it is as a multi-cell,

1:24:58 multi-tissue, multi-chemical phenomenon.

1:24:59 And before I listed off some of the things

1:25:01 that one could do in order to adjust hangover,

1:25:05 again, the one that comes out at the top of that list,

1:25:08 I believe, at least based on my read of the data,

1:25:10 is to support the gut microbiome and certainly not to ingest more alcohol.

1:25:16 And I suppose if we were to get really honest with one

1:25:20 another and ask what's the best way to avoid a hangover,

1:25:23 it would be to not drink in the first place.

1:25:25 So we've covered the major effects of alcohol that lead

1:25:28 to this state that we call drunkenness or inebriation.

1:25:33 Again, there's a range there.

1:25:34 You can be tipsy, people can be blackout drunk, people can be passed out drunk.

1:25:40 We've also talked about hangover and the fact that it's

1:25:43 a multifaceted phenomenon and recovery

1:25:45 from hangover involves a multifaceted approach.

1:25:49 Next I want to talk about tolerance.

1:25:51 Tolerance to alcohol is a very interesting phenomenon.

1:25:54 It has roots mainly in the brain and in brain systems.

1:26:00 There's not time in the world, let alone within this podcast,

1:26:03 to get into all the aspects of tolerance.

1:26:05 There are more than 10 different types of tolerance.

1:26:08 There's functional tolerance, chronic tolerance, rapid tolerance,

1:26:10 there's metabolic tolerance, there's psychological tolerance.

1:26:14 Let's keep it simple for sake of today's discussion.

1:26:16 And for those of you that are interested in learning

1:26:18 about all the different types of tolerance and aspects of tolerance,

1:26:22 there's an excellent review, we will provide a link to this.

1:26:25 This was published in 2021, so it's pretty recent,

1:26:27 in the journal "Pharmacology Biochemistry and Behavior." Incidentally,

1:26:31 or not so incidentally, that was the first journal I ever published

1:26:34 in so I have a particular affection for that journal.

1:26:38 Nonetheless, it is called Tolerance to alcohol:

1:26:41 A critical yet understudied factor in alcohol addiction.

1:26:44 And while this paper does include alcohol addiction in the title,

1:26:50 it's not just about alcohol addiction.

1:26:52 Here's the basic summary of what tolerance is.

1:26:54 First of all, tolerance refers to the reduced

1:26:57 effects of alcohol with repeated exposure,

1:27:01 and it is caused mainly by changes in neurotransmitter systems

1:27:04 in the brain that are the direct consequence of the toxicity of alcohol,

1:27:09 that aldehyde molecule that we talked about before.

1:27:12 There's an enormous number of chemicals

1:27:15 that change with repeated exposure to acetaldehyde,

1:27:20 everything from GABA to dopamine to serotonin,

1:27:22 second messenger systems, adenosine, and on and on.

1:27:25 Rather than go into each of those in detail,

1:27:27 I just want to talk about the contour

1:27:30 of the reinforcing and the tolerance-inducing effects of alcohol.

1:27:33 What do I mean by that?

1:27:34 Well, here we are back to our old friend,

1:27:38 meaning the molecule that comes up over and over

1:27:41 again in these podcast episodes, which is dopamine.

1:27:44 Whether or not somebody has a predisposition to alcoholism or not,

1:27:47 whether or not they're experienced drinker or not,

1:27:49 when people initially start drinking, there are increases in dopamine,

1:27:53 or what we call dopaminergic transmission.

1:27:55 Dopamine is involved in motivation, in craving,

1:27:58 it creates a sense of well-being,

1:28:00 it increases energy, again, typically only at the beginning of alcohol exposure.

1:28:05 That occurs in most people as a sharp spike, as a increase.

1:28:08 Again, if somebody does not have alcohol dehydrogenase or has very low levels

1:28:13 of the enzyme that convert that acetaldehyde

1:28:15 into acetate and that metabolize alcohol,

1:28:18 in other words, they will feel sick and lousy

1:28:20 in a way that will override any recognition of the dopamine release.

1:28:24 They're going to be the people that are listening to this and just thinking,

1:28:26 "Alcohol just makes me feel sick.

1:28:28 I don't like it." Okay, that's a specific subcategory of people,

1:28:31 but most people experience some sort of mild euphoria.

1:28:35 That's why so many people drink, right?

1:28:36 The current estimates are that in most countries, and certainly in the US,

1:28:40 as many as 80% of the adult, legal drinking age population drinks alcohol,

1:28:45 and that number could be even higher now because in the last couple of years,

1:28:49 there's been a trend towards increased alcohol consumption,

1:28:51 especially in the wake of the pandemic and during the pandemic.

1:28:56 Topic for another time.

1:28:57 So there's an increase in dopamine and an increase in serotonin,

1:29:01 so it's kind of an increase in well-being,

1:29:02 an increase in mood, but it's a very short-lived increase.

1:29:06 Very soon after, and actually triggered by that increase,

1:29:10 is a long and slow reduction in dopamine

1:29:14 and serotonin and related molecules in circuits.

1:29:17 So basically what you're getting is a blip of feel good followed by a long,

1:29:21 slow arc of feeling not so great, which is why,

1:29:24 typically, people will drink again and again across the night.

1:29:29 The key thing to understand about tolerance is that with tolerance,

1:29:34 the duration of that long,

1:29:36 slow reduction in dopamine and serotonin gets even longer.

1:29:42 In other words, the negative effects of alcohol

1:29:44 that happen after the initial feeling good,

1:29:47 extend longer and, in fact, get more robust.

1:29:52 However, there's also a reduction in the reinforcing properties of alcohol.

1:29:57 There's a shrinking of the feel good

1:29:59 blip that happens when one first ingests alcohol,

1:30:02 and this has been measured in animals and humans.

1:30:04 So the first drink that somebody has,

1:30:06 provided they have enough alcohol dehydrogenase so that doesn't

1:30:09 make them feel nauseous and sick right away, they feel really good.

1:30:13 And then as it wears off,

1:30:14 they feel kind of lousy and they want to drink more so they might drink more.

1:30:17 With each subsequent drink,

1:30:18 and even drinks on different nights or even different weeks,

1:30:23 the amount of dopamine that's released is reduced,

1:30:26 the amount of serotonin that's released is reduced.

1:30:29 So what you're getting is less

1:30:30 and less of the reinforcing properties of alcohol, the feel good stuff,

1:30:36 and more and more of the punishment pain signal aspects of alcohol.

1:30:39 This is the contour of chemical release in the brain

1:30:45 that was referred to by my colleague, the incredible Dr.

1:30:48 Anna Lembke, who's a medical doctor.

1:30:50 She wrote the incredible book "Dopamine Nation."

1:30:52 She was a guest on this podcast,

1:30:53 on Joe Rogan's podcast, on Rich Roll's podcast and several other podcasts.

1:30:57 World expert in addiction, and she talked about this pleasure-pain balance

1:31:01 that extends beyond alcohol to things like sex

1:31:04 and gambling and to other behaviors that can

1:31:07 potentially become addictive but certainly includes alcohol.

1:31:11 So tolerance, it seems, is a process in which people are ingesting more and more

1:31:17 alcohol as an attempt to get that feeling of well-being back,

1:31:22 but what they're really getting is an extended period of punishment,

1:31:25 of pain, and of malaise from the alcohol.

1:31:28 Now, you might say, "Well, how does that relate to tolerance?" Well,

1:31:31 it turns out what they do behaviorally, and when I say they,

1:31:34 I mean animals do this and humans do this, is they start drinking more

1:31:37 and more in an attempt to activate

1:31:39 those dopamine and serotonin neurons and receptors,

1:31:43 and as they do that, there is an increase in alcohol dehydrogenase,

1:31:48 so the enzyme that metabolizes alcohol is increased because

1:31:51 the body and liver have to contend with all that alcohol,

1:31:54 so now you've got, again, the two-hit model.

1:31:57 You're getting less of the feel good chemicals,

1:31:58 more of the negative chemical release,

1:32:01 or pattern of subjective feeling, I should say,

1:32:05 and you're metabolizing alcohol more quickly and more readily,

1:32:09 but it's not taking you to a better place in terms of how you feel.

1:32:13 That's one of the major underlying reasons for what we call tolerance.

1:32:16 So if you're somebody who drinks and you notice that the feeling that you

1:32:19 are seeking with alcohol is now requiring an additional drink, or drinks plural,

1:32:26 chances are you are disrupting the dopamine

1:32:29 and serotonergic systems of your brain, and you are doing that in a way that is

1:32:34 increasing the pain and punishment signals that follow alcohol ingestion.

1:32:40 And again, that's not just on the night

1:32:41 that you're drinking but afterwards as well.

1:32:43 Is that all bad news?

1:32:45 Well, pretty much.

1:32:46 But the good news is that if you abstain from drinking for some period of time,

1:32:50 then, of course, these systems reset.

1:32:52 How long you need to abstain will depend on how

1:32:54 much you were drinking and how long you were drinking for.

1:32:56 Certainly people who have alcohol use disorder or who are alcoholics,

1:33:00 their main goal should be to quit alcohol completely.

1:33:02 I know there's some debate about this, and I don't want to get

1:33:05 into that debate because I'm certainly not

1:33:06 going to try and direct anyone's recovery.

1:33:08 There are expert counselors and MDs and people that can work with people.

1:33:13 In fact, for some very heavy drinkers

1:33:15 and people with serious alcohol use disorder, going cold turkey, that is,

1:33:19 stopping drinking completely, can actually be medically dangerous.

1:33:22 So the path to sobriety for certain people looks

1:33:25 different than the path to sobriety for other people.

1:33:27 What I'm referring to here are people that are ingesting,

1:33:30 again, somewhere between, on average, one to two drinks per night,

1:33:34 whether or not that's done night to night

1:33:36 or whether or not that's condensed to weekend use.

1:33:39 I know a number of people are going to ask,

1:33:41 perhaps are screaming, "Is drinking good for me in any way?" For instance,

1:33:45 many people have probably heard that resveratrol is good

1:33:48 for people and that red wine is rich in resveratrol.

1:33:52 I hate to break it to you but the reality

1:33:53 is that if indeed resveratrol is good for us,

1:33:57 and there's some debate about this, some people say strongly yes,

1:33:59 some people say no, other people say maybe,

1:34:02 the amount of red wine that one would have to drink

1:34:06 in order to get enough resveratrol in order for it to be

1:34:09 health promoting is so outrageously high that it would surely induce

1:34:13 other negative effects that would offset the positive effects of resveratrol.

1:34:17 So I wish I could tell you different.

1:34:19 Again, I'm not here to be the bearer of bad news,

1:34:22 but the statement I just made was confirmed by Dr.

1:34:25 David Sinclair when he was a guest on this podcast.

1:34:27 It's confirmed by other researchers who

1:34:30 work on resveratrol and related pathways.

1:34:33 I wish I could tell you that red wine is good for your health,

1:34:35 and indeed it might be through some other mechanisms.

1:34:39 So, for instance, there have been studies

1:34:41 of low to moderate red wine consumption.

1:34:44 This would be anywhere from one to four glasses per week.

1:34:48 And I don't mean enormous glasses, I mean six-ounce glasses of red wine.

1:34:53 And in those cases, some of the stress reduction

1:34:56 that can be induced by consumption of red wine,

1:34:59 maybe some of the other micronutrients and components within red wines,

1:35:03 in particular red wines that come from particular grapes,

1:35:05 and this gets really nuanced and, frankly,

1:35:08 is not well worked out in the peer-reviewed

1:35:11 literature or certainly not clinical trials, at least not that I'm aware of.

1:35:14 Tell me if you're aware of a great clinical trial on this.

1:35:17 Well, there may be some positive effects of that very low level of consumption.

1:35:22 I'm not trying to take away anybody's red wine.

1:35:24 I'm not trying to take away anybody's anything.

1:35:27 I would be remiss, however,

1:35:29 if I didn't tell you that resveratrol as the argument for drinking,

1:35:36 and drinking red wine in particular, is just not a good one.

1:35:39 It's just not supported by the peer-reviewed research.

1:35:42 A few other things about alcohol and health.

1:35:45 At the beginning of the episode,

1:35:46 I referenced a study showing that indeed not just heavy

1:35:50 alcohol consumption of 12 to 24 or more drinks per week,

1:35:53 but also light to moderate alcohol consumption of any type, wine,

1:35:57 beer, spirits, et cetera, does reduce the thickness of the brain.

1:36:03 It really does reduce cortical thickness.

1:36:05 In fact, it actually scales with the amount of alcohol that people drink,

1:36:10 and this has been well-documented in a number of different studies.

1:36:13 I can provide a link to several of these.

1:36:16 One of the more striking ones

1:36:17 actually shows that there's almost a dose-dependent

1:36:20 increase in shrinkage of gray matter volume and in these white matter tracts,

1:36:24 these axons, these wires, as it were,

1:36:27 that connect different neurons as a function of how much alcohol people drink.

1:36:31 And that's also what's been seen in this recent study that I

1:36:34 referenced at the beginning and that's in the show note captions.

1:36:37 So, again, probably the best amount of alcohol to drink

1:36:40 would be zero glasses per week or ounces per week.

1:36:43 For those of you drinking low amounts of alcohol,

1:36:45 make sure you're doing other things to promote your health.

1:36:48 And for those of you that are drinking moderate

1:36:51 and certainly for those of you that are heavy drinkers,

1:36:53 please do everything you can to move away from that and to quit entirely.

1:36:58 But even for the moderate consumers of alcohol,

1:37:01 you are going to want to be aware of some of the negative health effects and do

1:37:05 things to offset those if indeed you're not

1:37:07 going to stop drinking or reduce your intake.

1:37:10 One of the really bad effects of alcohol,

1:37:12 but that's extremely well-documented, is the fact that alcohol,

1:37:18 because of this toxicity of acetaldehyde and the related pathways,

1:37:22 can alter DNA methylation, it can alter gene expression.

1:37:26 That can mean many things in different tissues,

1:37:28 but it is associated with a significant increase in cancer risk,

1:37:34 in particular, breast cancer, and in particular,

1:37:37 because breast tissue is present in both males and females,

1:37:40 but in women, it's especially vulnerable

1:37:43 to some of the DNA methylation changes, well,

1:37:46 breast cancer in women has a relationship to alcohol intake,

1:37:49 and alcohol intake has a relationship to breast cancer in women.

1:37:53 In fact, there has been proposed to be a anywhere from 4 to 13%

1:38:00 increase in risk of breast cancer for every 10 grams of alcohol consumed.

1:38:05 How much is 10 grams?

1:38:07 Well, there, we need to think a little bit about the variation

1:38:09 in the amount of alcohol and different drinks across the world.

1:38:12 Different countries serve different sized drinks and have

1:38:14 different concentrations of alcohol in those drinks.

1:38:16 So without going down too much of a rabbit hole and just

1:38:19 giving you some good rules of thumb to work with, there

1:38:22 have been studies of the percentage of alcohol included in different drinks

1:38:26 and the sizes of different drinks that are served in different countries,

1:38:28 and here's kind of a patchwork of those findings.

1:38:32 In Japan, one beer, one glass of wine, or one shot of liquor,

1:38:38 as it's served there,

1:38:40 tends to include anywhere from seven to eight grams of alcohol.

1:38:44 In the US, one beer, which generally is 12 ounces if it's in a bottle,

1:38:50 one glass of wine or a shot of liquor

1:38:52 tends to include about 10 to 12 grams of alcohol.

1:38:57 And in Russia, one drink of the various sorts that I

1:39:03 just described typically will have as much as 24 grams of alcohol

1:39:09 because of the differences in the concentration of alcohols and the sizes

1:39:13 of drinks that are poured in these different countries, okay?

1:39:16 Of course, there are other countries in the world,

1:39:18 those countries are also vitally important,

1:39:19 but those are the ones that I extracted from the studies that I could find.

1:39:25 What does this mean?

1:39:26 Well, what we're talking about is that for every 10 grams of alcohol consumed,

1:39:29 so that's one beer in the US, maybe a little bit more than one beer in Japan,

1:39:34 or basically a third of a drink in Russia,

1:39:38 there's a 4 to 13% increase in risk of cancer.

1:39:44 That's pretty outrageous, right?

1:39:46 And you might think, "Wait, how could it be that, you know,

1:39:49 this stuff is even legal?" Well, look, as I described before, it's a toxin.

1:39:54 It's also a toxin that people enjoy the effects of.

1:39:57 I mean, in the US at least, they tried prohibition.

1:40:00 It certainly did lead, yes,

1:40:02 did lead to a reduction in alcohol-induced health disorders,

1:40:08 in particular, cirrhosis of the liver.

1:40:09 It also led to a lot of crime because it became a substance that a lot

1:40:13 of people still wanted and that people were

1:40:16 willing to break the law in order to provide,

1:40:18 or, I should say, to sell and provide.

1:40:20 But the point is that the more alcohol people drink,

1:40:25 the greater their increase of cancer, in particular, breast cancer.

1:40:27 And that's because of the fact that alcohol has

1:40:31 these effects on cells that include changes in gene expression,

1:40:36 and cancer, that is, the growth of tumors,

1:40:39 is a dysregulation in cell cycles, right?

1:40:42 A tumor is a aggregation or the proliferation,

1:40:45 aggregation is stuff sticking together,

1:40:46 by the way, proliferation is stuff duplicating,

1:40:50 a proliferation or aggregation of cells that could be a glioma,

1:40:54 glial cells, glioma brain tumor, right?

1:40:56 It could be lymphoma, so within the lymph tissue, et cetera.

1:41:00 The mutations that alcohol induces to cause this are wide ranging,

1:41:05 some of those are starting to be understood.

1:41:07 For those of you that are interested in cell biology,

1:41:09 I'll just mention that the PD-1 pathway, again,

1:41:12 this is super specialized and for the aficionados only,

1:41:15 you don't need to know this, the PD-1 pathway seems

1:41:18 to be upregulated and, and we knew this from the discussion earlier,

1:41:21 there's a downregulation in some of the anti-inflammatory

1:41:27 molecules that help suppress this proliferation of cancers.

1:41:31 Nowadays, there's a lot of interest in the fact that the immune

1:41:34 system is constantly combating cancers that exist in us all the time.

1:41:38 You know, little tumors start growing

1:41:40 and our immune system goes and gobbles them up.

1:41:42 Little tumors start growing, the immune system senses inflammation,

1:41:45 sends out these incredible cells,

1:41:47 these killer B-cells and T-cells, and beats them up.

1:41:51 Cancers proliferate and take hold

1:41:53 and cause serious problems when the proliferation

1:41:56 of cells exceeds the immune system's ability

1:41:59 to gobble up and remove those cells.

1:42:00 There are other mechanisms of regulating cancers,

1:42:02 but that's one of the primary one.

1:42:04 And alcohol hits it.

1:42:05 Again, it's a two hit model.

1:42:07 It increases tumor growth and it decreases the sorts

1:42:11 of molecules that suppress and combat tumor growth.

1:42:15 So, again, even low to moderate amounts

1:42:17 of alcohol can be problematic for sake of cancers,

1:42:20 in particular, breast cancers.

1:42:23 Epidemiologists and health specialists love to try and compare

1:42:27 different substances in terms of how bad they are.

1:42:30 Rarely do they compare substances in terms of how good they are,

1:42:34 but sometimes they do.

1:42:35 And what they'll sometimes tell you and what you can find

1:42:38 in the literature is that ingesting 10 to 15 grams of alcohol a day,

1:42:42 so that would be like one beer in the US or one glass of wine,

1:42:45 is the same as smoking 10 cigarettes a day.

1:42:48 Frankly, it's hard to make that direct relationship really stick because,

1:42:54 you know, it's a question of, you know, how long people inhale,

1:42:57 do they have a predisposition to a lung cancer, et cetera.

1:43:00 But even if that number is off by plus or minus two cigarettes,

1:43:06 or even if that number was the equivalent

1:43:09 of one glass of wine equals one cigarette per day...

1:43:12 I think there's general consensus now

1:43:14 that nicotine consumed by vaping or by cigarette,

1:43:18 it's bad for us in terms of lung cancer and other forms of cancer.

1:43:24 And for some reason, I don't know why,

1:43:26 because this knowledge about alcohol and cancer and these established

1:43:31 relationships have been known since the late 1980s.

1:43:33 The first, you know, landmark paper on this was published in 1987.

1:43:37 I can provide a link to that paper.

1:43:38 It's actually quite interesting to read.

1:43:41 Well, the relationship is there and yet we don't often hear about it, right?

1:43:47 In fact, before researching this episode,

1:43:49 I had heard before that alcohol can increase cancer risk

1:43:52 but I wasn't aware of just how strong that relationship is.

1:43:56 Because of the serious nature of what we're talking about

1:43:58 and because I would hate to be confusing or misleading to anybody,

1:44:03 I want to just emphasize that this statistic, that there is a 4 to 13%,

1:44:07 depending on which study you look at, a 4

1:44:09 to 13% increase in the risk of cancer, in particular,

1:44:13 breast cancer, for every 10 grams of alcohol consumed,

1:44:17 that's 10 grams per day, so that's one drink per day.

1:44:20 But I do want to emphasize that if that equates to seven drinks

1:44:26 per week and all those seven drinks are being consumed on Friday and Saturday,

1:44:31 it still averages to 10 grams per day.

1:44:33 And I also want to emphasize that there are things

1:44:36 that people can do to at least partially offset some

1:44:39 of the negative effects of alcohol as it relates to predisposition

1:44:43 to the formation of certain kinds of tumors and cancers.

1:44:47 I also want to be clear before I say it that doing the things I'm

1:44:50 about to tell you is not a guarantee that you're not going to get cancer,

1:44:55 nor is it a guarantee that alcohol is not going

1:44:59 to lead to an increased predisposition for certain kinds of cancers,

1:45:03 and the two things are consumption

1:45:06 of folate and other B vitamins, especially B12.

1:45:10 You know, the consumption of folate and B12 has been

1:45:15 shown to decrease cancer risk in people that ingest alcohol,

1:45:19 but not completely offset it.

1:45:21 Why that is isn't exactly clear.

1:45:23 It probably has something to do with the relationship between folate and B12

1:45:27 and other B vitamins in gene regulation pathways that can lead to tumor growth.

1:45:34 At some point soon, we will get an expert in cancer biology, and, in particular,

1:45:38 in breast cancer biology, on the program and we can ask them about this.

1:45:42 But I realize this is going to raise a number of questions and maybe even cause

1:45:46 some of you to go out there and start

1:45:48 taking folate and other B vitamins and B12.

1:45:51 Not incidentally, a lot of the reported

1:45:55 hangover supplements and treatments include folate and B12.

1:46:00 I don't know if they had the cancer literature

1:46:02 in mind when they created those supplements and products.

1:46:06 I doubt they did.

1:46:07 Alcohol really does disrupt B vitamin pathways,

1:46:11 both synthesis pathways and utilization pathways,

1:46:14 so sometimes you'll hear, "Oh, you know, if you get your B vitamins,

1:46:16 it helps you recover from hangover more quickly." Again,

1:46:20 the literature doesn't support that, but also again,

1:46:23 there aren't a lot of studies.

1:46:24 But more to the point as it relates

1:46:27 to alcohol and the formation of tumors and cancers,

1:46:30 it does appear that decreased folate and other B vitamins like B12

1:46:35 are partially responsible for the effect of alcohol in increasing cancer risk.

1:46:40 And it does appear that consuming adequate amounts of folate in B12 might,

1:46:47 again, might partially,

1:46:48 really want to bold face and underline and highlight partially,

1:46:51 offset some of that increased risk.

1:46:54 There's an additional category that I want to highlight, of course,

1:46:58 and this is vitally important to state even though it's obvious,

1:47:02 which is that people who are pregnant should absolutely not consume alcohol.

1:47:09 Fetal alcohol syndrome is well known and established, it's terrible.

1:47:14 Fetuses experience diminished brain development that's often permanent,

1:47:19 diminished limb development,

1:47:21 diminished organ development in the periphery, meaning,

1:47:23 you know, the heart, the lungs, liver, et cetera.

1:47:25 Ingesting alcohol while pregnant is simply a bad idea.

1:47:28 And the reason I say this at all is, first of all,

1:47:32 it's important to include in an episode like

1:47:34 this, but also because we can look at two things.

1:47:37 First of all, we can look at mechanism and then we can

1:47:40 also look at some of the lore that still sadly exists out there.

1:47:44 Let's take care of the lore that sadly exists first.

1:47:48 If you look online, you will sometimes be able to find, sadly,

1:47:54 that some people believe that certain kinds

1:47:57 of alcohol are not detrimental to fetuses.

1:48:00 They'll say, "Well, champagne is safe for a pregnant mother

1:48:03 to drink but beer is not." That is absolutely categorically false.

1:48:08 Alcohol is alcohol.

1:48:09 There is no evidence whatsoever that consuming certain

1:48:12 types of alcohol is safer for fetuses than others.

1:48:15 Alcohol is a toxin, and the reason fetal alcohol syndrome exists

1:48:19 is because the ability of that toxin to disrupt cellular processes.

1:48:24 Remember tumor growth and the way that alcohol

1:48:27 can accelerate tumor growth by proliferation of cells,

1:48:30 the wrong cells, the ones you don't want to proliferate?

1:48:33 Well, all of embryonic development, all of fetal development,

1:48:37 it's not the growth of a tumor, it's obviously the growth of an embryo,

1:48:39 and it's done in a very orchestrated way.

1:48:43 I started off studying brain development.

1:48:45 That's where I got my beginnings in neurobiology,

1:48:47 and I still teach embryology to medical students and graduate students.

1:48:52 The set of coordinated processes that has to take place from conception

1:48:57 to birth in order to give rise to a healthy embryo is so,

1:49:01 so dynamically controlled and so exquisitely precise,

1:49:05 with checkpoints and recovery mechanisms and redundancy in the genes

1:49:09 that are expressed to make sure that if anything goes wrong,

1:49:11 it's repaired, et cetera.

1:49:13 Alcohol as a mutagen, I haven't used that word yet,

1:49:17 but a substance that can mutate DNA through alterations

1:49:21 in DNA methylation in these checkpoints in the cell cycle,

1:49:25 alcohol as a mutagen is one of the worst

1:49:28 things that a developing embryo can be exposed to.

1:49:31 And, again, because it's water-soluble and fat-soluble,

1:49:34 ingestion of alcohol when people are pregnant passes right to the fetus.

1:49:39 Now, I realize that a number of people

1:49:41 out there might be thinking, "Oh goodness,

1:49:42 you know, I didn't realize I was pregnant until a certain stage of pregnancy,

1:49:46 and before I realized, I was ingesting alcohol." Obviously,

1:49:50 one can't undo what's been done,

1:49:53 but I want to also emphasize that fetal alcohol syndrome, while, yes,

1:49:58 there's a full-blown syndrome that manifests as changes

1:50:00 in the cranial facial development that are very obvious,

1:50:02 and you can look these up,

1:50:03 you've probably seen these before, or the pictures before, rather,

1:50:06 it has to do with eye spacing, forehead size,

1:50:08 a number of other features of the cranial facial development,

1:50:11 and of course stuff's going on in the brain too, it's along a continuum.

1:50:15 So it is possible that some of the changes that occur are more minor,

1:50:20 and, thankfully, the young brain, in particular,

1:50:23 the early postnatal brain, is incredibly plastic.

1:50:25 There are things that can be done in order

1:50:27 to help recover neural circuits that didn't develop well, et cetera.

1:50:31 But even though it's somewhat obvious, or should be obvious,

1:50:36 I really want to make clear that there's zero evidence whatsoever that certain

1:50:39 forms of alcohol are safer for pregnant women to ingest than others.

1:50:42 Absolutely wrong, no one who's pregnant should be ingesting alcohol whatsoever.

1:50:48 And certainly, if people feel like they can't avoid alcohol while pregnant,

1:50:52 they really need to work with somebody to make sure that it

1:50:55 just absolutely doesn't happen because it

1:50:56 is so detrimental to the developing fetus.

1:50:58 Lastly, I want to talk about the effects of alcohol on hormones,

1:51:02 and I want to distinguish between low amounts of alcohol intake,

1:51:06 higher amounts of alcohol intake, and, again, this chronic alcohol intake

1:51:09 versus occasional use versus really chronic use,

1:51:13 meaning alcoholic or alcoholic use disorder,

1:51:16 where people are drinking an immense amount on an ongoing basis.

1:51:20 The literature on alcohol and hormones is quite extensive,

1:51:23 and there are, of course, many, many different types of hormones.

1:51:25 The hormones that most often get mentioned and talked

1:51:28 about on this podcast are the hormones testosterone and estrogen,

1:51:31 which are present in both men and women and that, in both men and women,

1:51:34 are important for things like libido,

1:51:38 they're also responsible for sexual development,

1:51:40 actual development of the genitalia before birth and after birth,

1:51:43 they're responsible, for instance,

1:51:45 estrogen is important for memory and cognition.

1:51:47 You never want to drop estrogen too low in men

1:51:49 or women 'cause it can disrupt cognition and joint health, et cetera.

1:51:54 To keep this discussion relatively constrained, it's fair to say that alcohol,

1:51:59 and, in particular, the toxic metabolites of alcohol,

1:52:03 increase the conversion of testosterone to estrogen.

1:52:07 Now, this occurs in a number of different tissues.

1:52:10 This is not just occurring in the testes of males,

1:52:12 this is occurring in lots of different tissues.

1:52:14 And I'll refer you to a excellent review.

1:52:16 We'll provide a link in the show note captions.

1:52:18 This is a paper that was published in the year

1:52:21 2000 but the data are still quite strong.

1:52:23 The journal is called, of all things, "Alcohol," yes,

1:52:28 literally a journal called "Alcohol" for the publication

1:52:32 of data and reviews on alcohol and its effects, and the title of the paper is

1:52:36 Can alcohol promote aromatization of androgens to estrogens?

1:52:39 Aromatization is this process of the conversion of testosterone

1:52:42 and other androgens to estrogens through things like aromatase enzyme.

1:52:46 And this is a beautiful review that describes every tissue,

1:52:50 or near every tissue,

1:52:52 from the ovary in females to the placenta to the liver to the testes,

1:52:58 in which alcohol can increase the aromatization of testosterone to estrogen.

1:53:04 Now, in females, this may be part

1:53:05 of the reason why there's an increase in estrogen-related cancers.

1:53:09 Breast cancer can be either estrogen-related or non-estrogen-related,

1:53:13 there are other types of estrogen-related cancers outside of breast cancer,

1:53:16 but it appears that one reason why alcohol increases the risk

1:53:19 of breast cancer is because of this aromatization from, of testosterone,

1:53:24 excuse me, to estrogen.

1:53:26 In males, accelerated or abnormal conversion of testosterone to estrogen

1:53:32 can actually lead to growth of the breast tissue in males,

1:53:35 so-called gynecomastia, or other effects of high estrogen,

1:53:39 or I should say of altered testosterone-estrogen ratios,

1:53:43 'cause that's really what's important.

1:53:45 And these can include things like diminished sex drive, increased fat storage,

1:53:49 and a number of other things that I

1:53:52 think most people would find to be negative effects.

1:53:56 I once talked about the fact that drinking

1:53:58 alcohol can increase the aromatization of testosterone to estrogen.

1:54:01 I posted that online, and I didn't get attacked but I did get

1:54:06 criticized for the fact that it has been shown,

1:54:08 yes, has been shown, that small amounts of alcohol ingestion,

1:54:11 so five grams or so of alcohol ingestion,

1:54:14 this would be half a glass of wine or half a glass of beer,

1:54:16 at least in some studies showed increases in testosterone,

1:54:19 which was kind of surprising.

1:54:21 But I should point out, other studies have shown that alcohol

1:54:25 ingestion causes decreases in testosterone over time.

1:54:29 So there's always this issue of whether or not you're

1:54:31 looking at a study of acute exposure versus chronic exposure,

1:54:33 you know, one dose versus multiple doses and exposure.

1:54:37 I think it's fair to say, based on my read of the literature,

1:54:41 this review and other reviews that focus more particularly on humans,

1:54:45 that regular ingestion of alcohol is going to increase

1:54:48 estrogen levels whether or not you're male or female,

1:54:50 and it's largely doing that through the aromatization process,

1:54:54 by increasing the aromatase enzyme.

1:54:57 Yes, there's some dose dependence, but I think if you're somebody

1:55:00 who's trying to optimize your testosterone-to-estrogen ratio,

1:55:03 regardless of whether or not you're male or female,

1:55:05 well then most certainly you're going

1:55:06 to want to avoid drinking too much alcohol.

1:55:09 So we've covered a lot of topics and data related to the mechanisms of alcohol,

1:55:14 hangover, tolerance, cancer risk, et cetera.

1:55:18 I acknowledge that I've mainly talked

1:55:19 to you about the negative effects of alcohol.

1:55:22 I want to acknowledge that many people

1:55:25 enjoy alcohol in moderation or even light drinking,

1:55:30 the occasional drink or the occasional two drinks or maybe even,

1:55:33 on average, one drink per night, so seven drinks per week.

1:55:37 I'm certainly not here to tell you what to do and what not to do.

1:55:40 I do find it immensely interesting, however, that, first of all,

1:55:45 alcohol is a known toxin to the cells of the body.

1:55:47 Some of you might immediately say, "Well, wait, what about hormesis?

1:55:50 What about this phenomenon where if we regularly ingest a toxin,

1:55:53 it makes us stronger?" In other words, what doesn't kill us makes us stronger.

1:55:57 Yeah, there's, you know, some reason to believe that might be beneficial

1:56:00 in terms of some forms of cellular resilience maybe, maybe.

1:56:04 No, sorry.

1:56:05 It doesn't work that way.

1:56:07 There are processes of hormesis in which, for instance,

1:56:11 exposing yourself safely through increases in adrenaline through, you know,

1:56:15 ice baths or other things that increase

1:56:17 adrenaline can raise your so-called stress threshold,

1:56:20 but here, we're talking about cellular stress and damage to cells.

1:56:24 So my read of the literature, and, again,

1:56:26 this is my read and I invite others to, you know,

1:56:30 provide studies or I would prefer actually collections

1:56:32 of studies that point in the direction, if they exist,

1:56:35 that alcohol can be beneficial, but my read of the literature,

1:56:41 or I should say my understanding of what I would call

1:56:44 the center of mass of the literature on alcohol is that no consumption,

1:56:49 zero consumption, consumption of zero ounces of alcohol is going to be

1:56:54 better for your health than low to moderate consumption of alcohol,

1:56:59 and that low to moderate consumption of alcohol

1:57:02 is going to be better for you, of course,

1:57:04 than moderately high to high alcohol consumption on the order

1:57:09 of 12 to 24 or more drinks per week.

1:57:13 I realize that for most people listening to this, it's probably

1:57:16 low to moderate alcohol consumption that is part of their standard repertoire,

1:57:23 and I'm not here to give you justification for doing

1:57:26 that nor am I going to tell you not to do that.

1:57:28 I would like you to consider perhaps, however,

1:57:31 the negative effects that we understand and that are documented.

1:57:34 For instance, the negative effects of alcohol on the gut microbiome

1:57:38 and the things that you can do to better support your gut microbiome,

1:57:42 the negative effects on the stress system,

1:57:45 that HPA axis that we talked about earlier,

1:57:47 and the fact that even low to moderate levels of alcohol

1:57:50 consumption can increase our levels of stress when we're not drinking,

1:57:53 and to think about acquiring some tools and, you know,

1:57:58 getting some proficiency with tools, behavioral or otherwise,

1:58:01 that can help you with stress modulation that don't involve alcohol consumption.

1:58:06 Again, the point here is to illustrate where

1:58:09 the problems lie with alcohol consumption, but, also,

1:58:11 what I've tried to do is to point you to some

1:58:14 resources that can help offset some of those negative effects.

1:58:17 Will they offset all the effects?

1:58:19 I can't say that for sure, but certainly taking measures to offset some

1:58:24 of the negative effects of any alcohol

1:58:26 consumption that you might be having or doing is going to be beneficial to you.

1:58:31 And those tools and protocols are going to be health-promoting in any case.

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2:00:05 I'd also like to point out that the Huberman Lab Podcast has a clips channel,

2:00:09 so these are brief clips, anywhere from 3 to 10 minutes,

2:00:13 that encompass single concepts and actionable protocols related to sleep,

2:00:18 to focus, interviews with various guests.

2:00:20 We talk about things like caffeine, when to drink caffeine, relative to sleep,

2:00:24 alcohol, when and how and if anyone should ingest it relative to sleep,

2:00:28 dopamine, serotonin, mental health, physical health,

2:00:30 and on and on, all the things that relate to the topics most of interest to you.

2:00:35 You can find that easily by going to YouTube,

2:00:37 look for Huberman Lab Clips in the search area and it will take you there.

2:00:41 Subscribe, and we are constantly updating those with new clips.

2:00:44 This is especially useful, I believe,

2:00:46 for people that have missed some of the earlier episodes

2:00:48 or you're still working through the back catalog of Huberman Lab Podcast,

2:00:50 which, admittedly, can be rather long.

2:00:53 And last, but certainly not least, thank you for your interest in science.

2:00:57 [upbeat music]