What Alcohol Does to Your Body, Brain & Health

00:00:00.000 | - Welcome to the Huberman Lab Podcast,

00:00:02.280 | where we discuss science and science-based tools

00:00:04.880 | for everyday life.

00:00:05.900 | I'm Andrew Huberman,

00:00:10.320 | and I'm a professor of neurobiology and ophthalmology

00:00:13.280 | at Stanford School of Medicine.

00:00:15.220 | Today, we're discussing alcohol,

00:00:17.280 | one of the most commonly consumed substances

00:00:19.180 | on the planet Earth.

00:00:20.520 | I should mention that both humans and non-human animals

00:00:23.220 | consume alcohol either for recreational purposes

00:00:26.680 | because they like the feeling that it gives them

00:00:29.760 | or for medicinal purposes

00:00:31.460 | or for other purposes that we'll discuss.

00:00:33.840 | We are of course going to discuss the effects of alcohol

00:00:36.520 | on our biology,

00:00:37.760 | ranging from its effects on individual cells,

00:00:40.500 | on organs and organ systems in our brain and body.

00:00:43.880 | We are also going to discuss the effects

00:00:45.680 | of the effects of alcohol.

00:00:47.460 | That is what being inebriated really does

00:00:49.960 | to our thinking and our behavior and how it does it.

00:00:52.440 | And we are going to address what seems to be

00:00:53.920 | one of the more common questions out there,

00:00:55.900 | which is whether or not low to moderate amounts of drinking

00:00:59.200 | are better for our health

00:01:00.360 | than zero alcohol consumption at all.

00:01:03.680 | And of course, we will talk about severe alcohol intake,

00:01:07.240 | binge drinking.

00:01:08.560 | We will also talk about hangover

00:01:10.240 | and what science says about ways

00:01:12.060 | to reduce the effects of hangover,

00:01:14.480 | either by doing things that are inoculatory,

00:01:16.440 | meaning before you drink or while you drink,

00:01:19.080 | as well as things to do if you happen to have a hangover.

00:01:22.640 | We will discuss some of the genetic differences

00:01:24.560 | for alcohol and alcoholism,

00:01:26.660 | and we will discuss alcohol consumption in young people

00:01:31.260 | and how that can be especially detrimental

00:01:33.440 | for reasons that I think are going to be quite surprising

00:01:35.520 | to most of you.

00:01:36.360 | My goal is that by the end of today's episode,

00:01:38.260 | you will have a thorough understanding

00:01:39.720 | of what alcohol does to your brain and body

00:01:41.740 | and that you will be able to make informed decisions

00:01:44.080 | as to whether or not you should be consuming

00:01:46.420 | zero, absolutely no alcohol,

00:01:48.840 | small to moderate amounts of alcohol.

00:01:51.080 | And again, we'll define exactly what that means,

00:01:54.200 | small to moderate amounts.

00:01:55.960 | And if you or somebody else that you know

00:01:58.080 | is consuming excessive amounts of alcohol

00:02:00.380 | that are clearly detrimental to your health,

00:02:02.520 | some of the better routes and resources that you can use

00:02:05.800 | in order to remove that dependence and/or consumption.

00:02:09.200 | I'd like to preface all of that by saying

00:02:11.780 | that today's discussion is really geared

00:02:14.320 | toward giving you information.

00:02:16.340 | It is not about judging alcohol intake

00:02:18.340 | or lack of alcohol intake.

00:02:19.960 | I just want you to be able to make

00:02:21.740 | the most informed decision about alcohol possible.

00:02:25.220 | I'm pleased to announce that the Huberman Lab Podcast

00:02:27.120 | is now partnered with Momentus supplements.

00:02:29.440 | We partnered with Momentus for several important reasons.

00:02:31.660 | First of all, they ship internationally

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00:03:03.820 | If you'd like to see the supplements

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00:03:06.280 | you can go to livemomentus.com/huberman.

00:03:09.380 | There you'll see those supplements.

00:03:10.500 | And just keep in mind that we are constantly expanding

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00:03:16.620 | Again, that's livemomentus.com/huberman.

00:03:19.180 | Before we get into today's content in detail,

00:03:21.860 | I just want to answer a commonly asked question

00:03:24.200 | about alcohol consumption and the brain.

00:03:26.460 | And the question that so often comes up

00:03:28.900 | is whether or not low to moderate amounts of alcohol,

00:03:31.900 | so maybe one drink a day or one or two drinks a day

00:03:34.580 | kind of thing, whether or not that is bad for your brain,

00:03:38.420 | in particular, whether or not it causes degeneration

00:03:40.600 | of neurons or nerve cells.

00:03:41.980 | Now, the reason that question comes up so often

00:03:44.300 | is because for many years it's been known

00:03:46.440 | that high levels of alcohol consumption,

00:03:48.340 | so 12 to 24 drinks per week or more,

00:03:52.380 | is certainly causing neurodegeneration,

00:03:55.060 | in particular of the so-called neocortex,

00:03:56.920 | the outer layers of the brain

00:03:58.780 | that house associative memories,

00:04:00.860 | that house our ability to think and plan,

00:04:03.140 | that house our ability to regulate our more primitive drives

00:04:07.700 | according to context, et cetera.

00:04:10.300 | So to make very clear, drinking a lot,

00:04:13.360 | so having three or four drinks per night

00:04:16.780 | every night of the week is clearly bad for the brain.

00:04:19.660 | A recent study, however, finally addressed the question

00:04:22.780 | of whether or not low to moderate amounts

00:04:25.100 | of alcohol consumption can cause brain degeneration.

00:04:28.840 | The title of the study is Associations

00:04:31.620 | between Alcohol Consumption and Gray and White Matter Volumes

00:04:35.040 | in the UK Biobank, the United Kingdom Biobank.

00:04:38.420 | First of all, gray matter are the neurons,

00:04:40.580 | it's the so-called cell bodies

00:04:41.860 | that house the genome of the cells, et cetera,

00:04:43.740 | and white matter is the connections, the fibers,

00:04:46.800 | the so-called axons of neurons,

00:04:48.780 | and it's called white matter because that tissue

00:04:52.300 | is surrounded by a fatty tissue called myelin,

00:04:54.500 | which allows nerve cells to communicate

00:04:56.260 | with each other very quickly.

00:04:57.580 | So what this study did is it looked at the brains,

00:05:00.580 | both the gray matter and the white matter,

00:05:02.480 | of more than 30,000, indeed more than 35,000,

00:05:06.460 | generally healthy middle-aged and older adults

00:05:09.140 | in the United Kingdom who were drinking

00:05:11.940 | various amounts of alcohol.

00:05:13.480 | What they found was that even for people

00:05:16.180 | that were drinking low to moderate amounts of alcohol,

00:05:20.020 | so one or two drinks per day,

00:05:22.460 | there was evidence of thinning of the neocortex,

00:05:27.040 | so loss of neurons in the neocortex and other brain regions.

00:05:30.820 | And I don't say this in order to cause alarm,

00:05:32.960 | I tell you this because they are important data,

00:05:36.080 | because they reveal and indeed answer the question

00:05:39.600 | that has been burning for so long

00:05:40.920 | as to whether or not chronic alcohol intake

00:05:44.340 | can disrupt the brain,

00:05:45.440 | even if the chronic intake is very low.

00:05:47.660 | Now, we should talk about what the word chronic means,

00:05:49.500 | because many people, when they hear the word chronic,

00:05:52.060 | think high levels of whatever intake, okay?

00:05:55.980 | So they think five drinks a night or 10 drinks a night

00:05:58.900 | or people drinking every night.

00:06:00.940 | Now, in this study, they looked at people who, on average,

00:06:03.380 | were drinking one or two drinks per night.

00:06:06.020 | So that could be 14 drinks on the weekend,

00:06:09.340 | it could be one drink per night,

00:06:11.820 | it could be seven drinks on Friday.

00:06:13.980 | In other words, on average, one or two drinks per night.

00:06:17.060 | And I think many people out there are drinking

00:06:19.120 | somewhere between one and two drinks per night

00:06:23.100 | or day of the week on average,

00:06:24.900 | so that would be seven to 14 drinks per week.

00:06:28.180 | So this is an important study,

00:06:29.500 | because it says that if you're consuming

00:06:31.500 | even just seven glasses of wine across the week,

00:06:34.140 | it's likely that there is going to be some degeneration

00:06:37.000 | of your brain in response to that alcohol intake.

00:06:40.160 | Although, as mentioned earlier,

00:06:41.960 | we will talk about some of the things that can inoculate

00:06:44.440 | against some of that neuronal loss.

00:06:46.300 | For those of you that are interested

00:06:47.440 | in reading the study in more detail,

00:06:50.060 | we've put a link to it in the show note captions.

00:06:52.360 | Before we begin, I'd like to emphasize that this podcast

00:06:54.920 | is separate from my teaching and research roles at Stanford.

00:06:57.460 | It is, however, part of my desire and effort

00:06:59.580 | to bring zero cost to consumer information about science

00:07:02.040 | and science-related tools to the general public.

00:07:04.700 | In keeping with that theme,

00:07:05.720 | I'd like to thank the sponsors of today's podcast.

00:07:08.500 | Our first sponsor is Levels.

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00:07:31.420 | And that's because all the cells and tissues of our body,

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00:10:47.140 | Let's talk about alcohol.

00:10:48.340 | And let's just acknowledge that human beings

00:10:49.740 | have been consuming alcohol for thousands of years.

00:10:52.040 | If you look at the archeological evidence from Mesopotamia,

00:10:54.520 | you'll find that 5,000 years ago, people had wine vessels.

00:10:57.180 | Or if you want to know when people first started

00:10:59.340 | distilling alcohol, much to people's surprise,

00:11:01.820 | that did not first take place in Ireland.

00:11:03.880 | And that's not a joke about the Irish,

00:11:05.120 | that you'll see a lot of claims online

00:11:06.720 | that the Irish were the first to distill alcohol,

00:11:08.620 | but in fact, they were not.

00:11:10.200 | It was the Chinese that were the first to distill alcohol

00:11:12.520 | and that took place in China in the first century.

00:11:15.320 | Alcohol has been used for nutritional purposes.

00:11:17.700 | So there are cultures that believe and indeed still believe

00:11:21.480 | that the calories in alcohol are useful.

00:11:23.600 | Although later we'll talk about how alcohol calories

00:11:25.580 | are indeed empty calories

00:11:26.860 | and what an empty calorie really is, why it's called empty.

00:11:30.260 | Alcohol has been used for medicinal purposes

00:11:33.480 | because indeed it does kill bacteria.

00:11:35.500 | And as you'll soon find out, the fact that it kills bacteria

00:11:38.380 | because that is absolutely true,

00:11:40.700 | it also kills the good bacteria in your gut

00:11:42.520 | and the destruction of that good bacteria in your gut

00:11:44.720 | can lead to things like leaky gut syndrome

00:11:47.040 | and has all sorts of issues

00:11:48.200 | and there are ways to deal with those issues

00:11:49.560 | and we'll talk about those.

00:11:50.800 | So alcohol has been used for medicinal purposes.

00:11:52.860 | It's been used to clean surfaces.

00:11:54.220 | It's used in my laboratory in order to make up

00:11:56.760 | so-called reagents to do our experiments.

00:11:59.700 | But most humans have been consuming alcohol

00:12:02.560 | in order to change their internal state,

00:12:04.360 | in order to feel differently than they would otherwise.

00:12:07.520 | That feeling of being drunk or inebriated

00:12:09.720 | or tipsy or lightheaded is something that many, not all,

00:12:13.720 | but many humans seem to enjoy and pursue

00:12:16.480 | even though typically it leads to a feeling

00:12:20.520 | of being less happy, less motivated, more stressed, et cetera

00:12:25.520 | when the alcohol wears off.

00:12:28.120 | That's pretty incredible, right?

00:12:29.180 | I mean, we're talking about a substance

00:12:30.760 | that people have been highly motivated to pursue,

00:12:32.780 | that are still highly motivated to pursue,

00:12:34.960 | to create and to consume, that they'll spend money on.

00:12:38.480 | And that's despite the fact that it makes them feel good

00:12:41.920 | and then it makes them feel lousy.

00:12:43.480 | Now, some of you might be saying,

00:12:44.480 | well, I drink, but I don't drink to excess

00:12:46.420 | and therefore I don't feel lousy.

00:12:48.080 | I feel good when I drink and then it wears off

00:12:50.120 | and it allows me to get through my evening

00:12:51.720 | and then the next morning I'm ready to go.

00:12:53.880 | Okay, that very well may be true, I believe those people.

00:12:58.480 | And as I mentioned at the beginning of the episode,

00:13:00.120 | I'm not here to demonize alcohol in any way,

00:13:02.720 | but I do want to point out what alcohol is

00:13:05.680 | and how it creates the effects that it does.

00:13:08.560 | And then I want to talk about what those effects are

00:13:11.400 | when you engage in consuming alcohol,

00:13:14.760 | even as often as one or two nights per week,

00:13:17.560 | or let's say you're just somebody

00:13:18.760 | who has a drink or two on Friday,

00:13:20.360 | maybe a few more on Saturday,

00:13:21.740 | or maybe you're somebody who consumes all your alcohol

00:13:24.240 | one night per week or one night per month.

00:13:25.920 | We'll talk about how that's affecting your biology.

00:13:28.380 | So let's address what alcohol is

00:13:31.120 | and how it affects the cells and tissues

00:13:32.700 | and organs of your body.

00:13:33.740 | Then we'll take a look at some of the epidemiology,

00:13:36.200 | that is how many people are consuming alcohol

00:13:38.240 | and how much they're drinking.

00:13:39.760 | And then you will be able, I think,

00:13:41.100 | to get a good sense of how the alcohol that you're drinking,

00:13:44.560 | if you're drinking any at all,

00:13:46.860 | is impacting your brain and body

00:13:48.480 | and the choices you might want to make

00:13:50.200 | about how and when to drink alcohol,

00:13:52.760 | or even if you want to eliminate alcohol altogether.

00:13:55.160 | Okay, so some basic chemistry and biology of alcohol.

00:13:58.160 | And again, I'll make this very clear,

00:13:59.720 | even if you don't have a chemistry and biology background,

00:14:02.480 | because of the structure of alcohol,

00:14:04.800 | it is what's called both water soluble and fat soluble,

00:14:08.860 | translated into what's meaningful for you.

00:14:11.540 | What that means is when you drink alcohol,

00:14:13.840 | it can pass into all the cells and tissues of your body.

00:14:17.560 | It has no trouble just passing right into those cells.

00:14:20.920 | So unlike a lot of substances and drugs

00:14:23.860 | that actually attach to the surface of cells,

00:14:26.080 | to receptors as they're called, little parking spots,

00:14:28.360 | and then trigger a bunch of downstreams,

00:14:31.480 | like domino cascades of effects,

00:14:33.840 | alcohol actually has its own direct effects on cells

00:14:36.720 | because it can really just pass into those cells.

00:14:39.460 | So it's water and fat soluble.

00:14:41.960 | And the fact that it can pass into so many organs and cells

00:14:45.160 | so easily is really what explains its damaging effects.

00:14:49.440 | I should mention that there are three main types of alcohol.

00:14:52.040 | There's isopropyl, methyl, and ethyl alcohol,

00:14:55.440 | and only the last one, ethyl alcohol or ethanol,

00:14:58.560 | is fit for human consumption.

00:15:00.440 | However, it is still toxic, okay?

00:15:03.480 | It produces substantial stress and damage to cells.

00:15:07.880 | I'd love to be able to tell you otherwise,

00:15:09.340 | but that's just a fact.

00:15:10.900 | Ethanol produces substantial damage to cells.

00:15:14.400 | And it does that because when you ingest ethanol,

00:15:17.720 | it has to be converted into something else

00:15:19.520 | because it is toxic to the body.

00:15:21.640 | And there's a molecule inside of all of us called NAD.

00:15:25.100 | And you may have heard of NAD because it's quite popular.

00:15:27.700 | There's a lot of discussion about NAD

00:15:30.140 | in the longevity literature right now.

00:15:32.000 | NAD is present in all our cells from birth until death.

00:15:34.680 | The levels of NAD tend to go down across the lifespan.

00:15:37.400 | There are ideas that increasing levels of NAD

00:15:39.720 | may extend lifespan.

00:15:40.740 | A lot of that is still controversial,

00:15:42.300 | or at least we should say is ongoing

00:15:43.880 | in terms of the research.

00:15:45.260 | But nonetheless, when you ingest ethanol,

00:15:47.520 | NAD and related biochemical pathways

00:15:50.160 | are involved in converting that ethanol

00:15:52.440 | into something called acetaldehyde.

00:15:54.040 | It's broken down into acetaldehyde.

00:15:56.540 | And if you thought ethanol was bad,

00:15:58.120 | acetaldehyde is particularly bad.

00:15:59.920 | Acetaldehyde is poison.

00:16:01.960 | It will kill cells.

00:16:03.040 | It damages and kills cells.

00:16:04.640 | And it is indiscriminate as to which cells

00:16:06.640 | it damages and kills.

00:16:08.960 | Now, that's a problem, obviously.

00:16:11.840 | And the body deals with that problem

00:16:14.000 | by using another component of the NAD biochemical pathway

00:16:18.400 | to convert acetaldehyde into something called acetate.

00:16:22.680 | Acetate is actually something

00:16:23.960 | that your body can use as fuel.

00:16:26.220 | And that process of going from ethanol

00:16:29.440 | to acetaldehyde to acetate

00:16:31.200 | does involve the production of a toxic molecule, right?

00:16:35.400 | Again, acetaldehyde is really toxic.

00:16:37.600 | And NAD, and if we want to get technical,

00:16:40.080 | it's the NAD to NADH ratio.

00:16:43.480 | And that chemical step is the rate limiting step

00:16:47.460 | to ethanol's metabolism.

00:16:48.680 | What does that mean for you?

00:16:50.180 | What that means is that if your body

00:16:52.460 | can't do this conversion of ethanol

00:16:54.400 | to acetaldehyde to acetate fast enough,

00:16:57.180 | well, acetaldehyde will build up in your body

00:16:59.540 | and cause more damage.

00:17:01.180 | So it's important that your body be able

00:17:03.320 | to do this conversion very quickly.

00:17:05.840 | And the place where it does that is within the liver.

00:17:09.160 | And cells within the liver are very good

00:17:11.760 | at this conversion process,

00:17:13.640 | but they are cells and they are exposed to the acetaldehyde

00:17:16.960 | in the conversion process.

00:17:18.600 | And so cells within the liver really take a beating

00:17:21.160 | in the alcohol metabolism events.

00:17:25.440 | So the key thing to understand here is that

00:17:28.480 | when you ingest alcohol, you are, yes, ingesting a poison.

00:17:31.380 | And that poison is converted

00:17:32.760 | into an even worse poison in your body.

00:17:34.460 | And some percentage of that worst poison

00:17:36.440 | is converted into a form of calories that you can use

00:17:39.260 | to generate energy, generate ATP.

00:17:42.200 | And the reason why alcohol is considered empty calories

00:17:45.480 | is because that entire process is very metabolically costly,

00:17:48.740 | but there's no real nutritive value

00:17:51.080 | of the calories that it creates.

00:17:53.360 | You can use it for immediate energy,

00:17:55.280 | but it can't be stored

00:17:56.600 | in any kind of meaningful or beneficial way.

00:17:58.800 | It doesn't provide any vitamins.

00:18:00.440 | It doesn't provide any amino acids.

00:18:02.120 | It doesn't provide any fatty acids.

00:18:04.000 | It's truly empty calories.

00:18:05.880 | I know some people talk about sugar is empty calories,

00:18:07.960 | but sugar actually is a far better fuel source

00:18:10.640 | than alcohol or acetate.

00:18:13.160 | But nonetheless, when you ingest alcohol,

00:18:16.100 | some percentage is being shuttled into a worse poison

00:18:19.240 | and some is being shuttled into a fuel source.

00:18:22.660 | Now, the important thing to understand

00:18:24.400 | is that it is the poison, the acetaldehyde itself,

00:18:28.260 | that leads to the effect of being inebriated or drunk.

00:18:32.760 | I think most people don't realize that,

00:18:34.080 | that being drunk is actually a poison-induced disruption

00:18:38.400 | in the way that your neural circuits work.

00:18:40.320 | And so we should ask ourselves which neural circuits,

00:18:43.400 | what brain areas, what body areas involved

00:18:45.800 | in feeling drunk or inebriated.

00:18:47.740 | Now, in thinking about this state of being tipsy or happy

00:18:50.560 | or really drunk or a little bit drunk,

00:18:53.440 | I want to mention something

00:18:54.660 | I think most people aren't aware of.

00:18:56.920 | And that's the fact that for people

00:18:59.040 | that are regular drinkers

00:19:00.680 | or that have a genetic predisposition to alcoholism,

00:19:04.900 | when they drink, they tend to feel very energized

00:19:08.240 | and very good for longer periods of time.

00:19:11.540 | Again, people have a genetic predisposition to alcohol

00:19:14.080 | or people who are chronic drinkers,

00:19:15.520 | or even just, if you recall,

00:19:17.200 | chronic doesn't have to mean a ton of alcohol,

00:19:19.460 | but they're drinking one or two per night

00:19:21.080 | or they're every other night type drinkers

00:19:22.880 | or Thursday through Sunday drinkers.

00:19:24.640 | Those people typically experience an increase

00:19:28.840 | in alertness and mood when they drink,

00:19:31.000 | whereas occasional drinkers will have a briefer,

00:19:34.640 | meaning less long lasting,

00:19:36.900 | period of feeling good when they drink

00:19:38.800 | and then more quickly transition into a state

00:19:41.620 | in which they're tired or they start losing motor skills,

00:19:44.440 | they start slurring their speech.

00:19:46.080 | I also want to emphasize this is distinct from tolerance.

00:19:49.620 | We'll talk about tolerance later

00:19:50.800 | and exactly what tolerance means.

00:19:52.520 | But I really want to highlight the fact

00:19:53.900 | that when people ingest this poison,

00:19:56.960 | 'cause indeed it is poison,

00:19:59.080 | the range of effects is very different

00:20:01.040 | and you can reliably predict who are the people

00:20:04.120 | with a predisposition to alcoholism

00:20:06.400 | and who are the people who are more regular drinkers

00:20:09.240 | by the contour, the timing of the different effects.

00:20:12.480 | And again, people who tend to feel more alert and excited

00:20:16.800 | every time they drink, they tend to get a real lift.

00:20:19.560 | They become kind of the life of the party

00:20:21.000 | and that lasts a long while.

00:20:23.320 | Those people are the ones that really have to be careful

00:20:26.040 | about predisposition for alcoholism.

00:20:29.080 | And those people also need to be careful

00:20:31.620 | about their drinking and the amount of drinking

00:20:34.000 | that they're doing, even if they're not full blown alcoholics.

00:20:37.420 | Now, of course, people who are ingesting alcohol,

00:20:39.800 | who are not accustomed to drinking alcohol

00:20:41.120 | have to be concerned about drinking alcohol for other reasons

00:20:43.560 | because it can impair motor function and judgment, et cetera.

00:20:46.680 | But in thinking about the biochemical effects of alcohol

00:20:49.800 | and what it's doing to the body,

00:20:51.600 | what it's doing in all cases is it's consumed into the gut,

00:20:56.600 | goes into the stomach,

00:20:57.840 | the liver immediately starts this conversion

00:20:59.700 | that we talked about before

00:21:00.640 | of ethanol to acetaldehyde to acetate.

00:21:02.880 | And some amount of acetaldehyde and acetate

00:21:05.040 | are making it into the brain.

00:21:06.180 | It crosses the blood-brain barrier.

00:21:07.660 | Again, the brain has this fence around it

00:21:09.580 | that we call the blood-brain barrier or the BBB.

00:21:12.120 | Many things, most things thankfully,

00:21:14.640 | can't pass across the blood-brain barrier,

00:21:16.800 | but alcohol because it's water and fat soluble

00:21:19.040 | just cruises right across this fence

00:21:21.040 | and into the milieu, the environment of the brain,

00:21:24.220 | which is made up of a couple of different major cell types,

00:21:26.340 | neurons, nerve cells, and so-called glial cells,

00:21:28.640 | which are in between the nerve cells.

00:21:30.640 | And we'll talk about the effects on each of those soon.

00:21:33.640 | So what happens when alcohol gets into the brain

00:21:35.560 | that makes us feel tipsy or drunk

00:21:37.100 | and in some people makes people feel really,

00:21:39.980 | especially energized and happy?

00:21:42.040 | Well, alcohol is indiscriminate

00:21:44.900 | in terms of which brain areas it goes to.

00:21:47.540 | Again, it doesn't bind to particular receptors,

00:21:49.980 | but it does seem to have a propensity or an affinity

00:21:53.920 | for particular brain areas that are involved

00:21:55.560 | in certain kinds of thinking and behavior.

00:21:57.280 | So one of the first things that happens

00:21:59.400 | is that there's a slight,

00:22:01.200 | at least after the first drink or second drink,

00:22:04.100 | there's a slight suppression in the activity of neurons

00:22:07.600 | in the prefrontal cortex.

00:22:08.980 | This is an area of your neocortex

00:22:11.240 | that's involved in thinking and planning

00:22:13.300 | and perhaps above all in suppression of impulsive behavior.

00:22:18.520 | So if you go to a party and they're serving alcohol

00:22:21.400 | and people are consuming drinks,

00:22:22.980 | what you'll notice is that a few minutes into that party,

00:22:25.960 | the volume of people's voices will increase.

00:22:28.240 | And that's because people are simply not paying attention

00:22:30.440 | to their voice modulation.

00:22:31.680 | As other people start speaking more loudly,

00:22:33.400 | other people are speaking more loudly.

00:22:34.640 | We've all had this experience, right, of going to a party

00:22:36.560 | and then you step outside for a moment and you go,

00:22:38.360 | "Oh my goodness, I was shouting."

00:22:39.680 | You come home the next day, you got a sore throat.

00:22:41.400 | It might be that you picked up some sort of bug,

00:22:43.200 | some virus or something.

00:22:44.600 | But oftentimes it's just the fact

00:22:46.520 | you've been shouting all night just to be heard

00:22:48.080 | because as the prefrontal cortex shuts down,

00:22:50.500 | people stop modulating their level of speech quite as much.

00:22:55.060 | Also notice that people start gesticulating more.

00:22:57.420 | People will start standing up and sitting down more.

00:22:59.760 | They'll start walking around more.

00:23:00.860 | If there's music on,

00:23:01.700 | people might spontaneously start dancing.

00:23:04.000 | All of this is because these areas of the prefrontal cortex

00:23:07.160 | normally are providing what's called top-down inhibition.

00:23:10.000 | They are releasing a neurotransmitter called GABA

00:23:13.160 | onto various parts of the brain.

00:23:14.800 | They're involved in impulsive motor behavior

00:23:16.680 | and thought patterns.

00:23:17.920 | And as you shut down the prefrontal cortex,

00:23:20.040 | that GABAergic suppression of impulses starts to be released.

00:23:24.440 | So people will say things that they want to say

00:23:27.400 | without so much forethought about what they're saying.

00:23:30.360 | Or they might do things that they want to do

00:23:32.800 | without really thinking it through quite as much

00:23:34.880 | or they might not even remember thinking it through at all

00:23:37.280 | or experience, I should say, thinking it through at all.

00:23:39.260 | We haven't talked about blacking out yet

00:23:40.680 | in the effects of alcohol on memory.

00:23:42.560 | But as long as we're there,

00:23:43.520 | I'll just tell you that alcohol has a very strong effect

00:23:46.600 | in suppressing the neural networks

00:23:48.280 | that are involved in memory formation and storage.

00:23:51.160 | This is why oftentimes we forget the events of a night out

00:23:55.000 | if we've been drinking.

00:23:56.780 | One of the more important things to know

00:23:58.520 | about the effects of alcohol in the brain

00:24:01.000 | is this disruption in top-down inhibition,

00:24:03.840 | but also that areas of the brain

00:24:06.820 | that are involved in flexible behavior,

00:24:09.680 | sort of considering different options,

00:24:11.200 | like I could do A or I could do B.

00:24:12.640 | I could say this to them or I could say that.

00:24:14.480 | I could say it in that way

00:24:15.600 | or I could say it in this way.

00:24:16.600 | This might be a little more tactful.

00:24:18.560 | Those brain areas basically shut down entirely

00:24:21.680 | and people just tend to say what they want to say.

00:24:23.840 | So the key thing to understand is that when people drink,

00:24:26.560 | the prefrontal cortex and top-down inhibition is diminished.

00:24:31.160 | That is habitual behavior

00:24:33.280 | and impulsive behavior starts to increase.

00:24:36.100 | Now, what's interesting is this is true in the short term,

00:24:39.180 | so after people have one or two,

00:24:40.640 | maybe three or four drinks,

00:24:42.260 | but it's also true that the more often that people drink,

00:24:47.040 | there are changes in the very circuits

00:24:50.540 | that underlie habitual and impulsive behavior.

00:24:53.500 | Okay, this is really important to highlight,

00:24:55.160 | so much so that I want to drill into it

00:24:56.480 | a little bit more deeply.

00:24:57.760 | For the person that drinks, say, every Thursday night

00:25:01.700 | or every Friday night,

00:25:02.800 | or goes out only on Saturdays, but every Saturday,

00:25:06.260 | there's evidence that there are changes

00:25:08.140 | in the neural circuits of the brain

00:25:09.740 | that control habitual behavior and impulsive behavior,

00:25:12.800 | and they are modified and strengthened

00:25:15.540 | in ways that make those people more habitual

00:25:18.280 | and more impulsive outside the times

00:25:21.080 | in which they are drinking.

00:25:22.700 | And when they drink, impulsive and habitual behavior

00:25:26.040 | tends to increase even further.

00:25:27.800 | This is something that's not often talked about

00:25:30.120 | when discussing the effects of alcohol.

00:25:31.840 | And we all know the effects of being drunk can be bad,

00:25:36.120 | can be bad in terms of judgment, motor coordination,

00:25:39.360 | certainly driving drunk is a terrible thing,

00:25:41.680 | get you or other people killed, and so on.

00:25:44.600 | But rarely do we hear about the changes in neural circuits

00:25:47.640 | from just one or two nights of regular drinking.

00:25:52.440 | Again, chronic drinking doesn't necessarily mean

00:25:55.120 | every day and every night.

00:25:56.600 | It could be the person that simply drinks

00:25:58.300 | every Thursday or every Friday,

00:25:59.580 | or just once a week has three or four drinks,

00:26:01.220 | or maybe even a few more.

00:26:03.000 | That person is going to experience

00:26:04.960 | a decrease in this top-down inhibition,

00:26:07.600 | so an increase in impulsivity and habitual behavior

00:26:09.880 | because the break on those behaviors

00:26:11.840 | has been removed while they're drinking,

00:26:13.720 | but also changes in the very neural circuits

00:26:16.360 | that allow habitual and impulsive behavior

00:26:19.000 | to occur more readily even when they're not drinking.

00:26:21.480 | And if you want to know the actual substrate for that,

00:26:23.680 | the cellar substrate, I can briefly describe it.

00:26:25.640 | It's really interesting.

00:26:27.040 | Again, you don't need to know any biology

00:26:28.340 | to understand this.

00:26:29.240 | What it does is it increases the number of synapses,

00:26:33.000 | the actual points of connection in the neural circuits

00:26:35.300 | that control habitual behavior.

00:26:37.780 | So there's literally a growth of the neural circuits

00:26:40.580 | in your brain that lead to existing habit execution, right?

00:26:44.820 | The performance of things you already know how to do

00:26:47.180 | and a reduction in the neural circuits,

00:26:49.760 | or I should say a reduction in the number of synapses

00:26:52.100 | of the contacts within the neural circuits

00:26:54.720 | that are controlling behavior.

00:26:56.540 | So this again is a not often discussed aspect

00:26:59.000 | of alcohol intake.

00:27:00.140 | Fortunately, it is reversible.

00:27:02.200 | So in animals or humans that undertake a period of abstinence

00:27:06.460 | of anywhere from two to six months,

00:27:08.920 | these neural circuits return to normal,

00:27:11.260 | except in cases where people have been chronically drinking

00:27:14.140 | large volumes of alcohol for many, many years.

00:27:16.280 | And in those cases,

00:27:17.540 | while there is some recovery of brain circuitry,

00:27:20.840 | after people get sober, meaning completely sober,

00:27:24.100 | they stop drinking entirely,

00:27:25.980 | there is evidence of long lasting impact

00:27:28.580 | of heavy alcohol usage throughout the lifespan.

00:27:31.240 | But of course, this doesn't mean that anyone

00:27:32.860 | that's suffering from alcoholism or that used to

00:27:34.780 | should not continue to focus on their health.

00:27:36.880 | You absolutely should, all is not lost.

00:27:39.280 | But for people that have been drinking for a lot of years,

00:27:40.980 | maybe you went to college and you drank a lot in those years

00:27:43.520 | and your neural circuits change.

00:27:45.380 | If there's a period in which you don't drink alcohol,

00:27:47.820 | again, from two to six months and ideally longer,

00:27:51.580 | those neural circuits can then be re-modified

00:27:53.660 | back to their original state.

00:27:55.260 | So let's consider some of the other neurochemical effects

00:27:57.740 | of alcohol in the brain and body.

00:27:59.340 | And again, for right now, we're confining the conversation

00:28:02.580 | to people that are drinking on average,

00:28:04.560 | one or two drinks per night.

00:28:06.300 | Now, some people might think that two drinks per night

00:28:07.920 | is a lot and a lot of that will depend on body weight.

00:28:10.380 | So for instance, people who weigh 110 pounds,

00:28:15.380 | for them to ingest two alcoholic drinks

00:28:18.340 | is going to be substantially different

00:28:19.820 | in terms of the biochemical effects

00:28:21.580 | than somebody who weighs 220 pounds.

00:28:24.260 | Of course, tolerance will also factor into this,

00:28:26.840 | genetic background will also factor into this,

00:28:29.480 | and indeed, whether or not people have eaten

00:28:32.100 | will factor into this.

00:28:32.940 | So there are a lot of factors and we'll talk about that.

00:28:35.000 | For the time being, if you're curious about how food impacts

00:28:38.440 | the effects of alcohol and your feelings of being drunk,

00:28:41.360 | you may have heard, for instance,

00:28:42.560 | that if somebody is inebriated and they want to sober up,

00:28:45.020 | they should eat something, turns out that does not work.

00:28:48.080 | Here's how it does work, however.

00:28:50.100 | If you eat something prior to drinking alcohol

00:28:53.280 | or while ingesting alcohol,

00:28:55.800 | it will slow the absorption of alcohol into the bloodstream.

00:28:59.700 | In other words, you won't feel as drunk as fast.

00:29:02.020 | For many of you, this probably comes as no surprise,

00:29:04.220 | in particular, if that meal includes carbohydrates,

00:29:07.460 | fats, and proteins, okay?

00:29:09.660 | The inclusion of all three major macronutrients

00:29:12.800 | seems to slow the absorption of alcohol into the bloodstream

00:29:15.620 | far more than having any one of those

00:29:18.520 | or two of those macronutrients present.

00:29:21.220 | Now, if you are already inebriated

00:29:23.700 | or you've had a glass of wine or a beer

00:29:25.840 | and you eat something,

00:29:27.880 | chances are that alcohol has already made it

00:29:30.960 | into your bloodstream

00:29:31.780 | because it moves into the bloodstream so quickly.

00:29:34.940 | Again, it's fat soluble and water soluble,

00:29:37.060 | so within minutes, right?

00:29:38.360 | If you have an empty stomach,

00:29:40.000 | within five to 10 minutes,

00:29:41.560 | that alcohol is going to be within your bloodstream

00:29:43.320 | and distributed throughout your body,

00:29:44.360 | maybe even faster depending on the type of alcohol

00:29:46.640 | and your metabolism.

00:29:48.600 | But if you're already drunk and you eat something,

00:29:52.240 | it's not going to sober you up more quickly,

00:29:53.780 | but it certainly will blunt the effects

00:29:55.080 | of any additional alcohol that you might consume.

00:29:57.900 | And if you're somebody who is concerned

00:30:00.440 | about getting too drunk too quick,

00:30:02.160 | even from a small amount of alcohol,

00:30:03.380 | having some food in your gut can certainly be beneficial.

00:30:06.860 | Now, that's food and alcohol and the absorption of alcohol,

00:30:10.260 | but let's go back to talking about the biochemical

00:30:13.340 | and neurochemical effects of alcohol on the brain.

00:30:15.900 | We talked about top-down inhibition

00:30:17.960 | and we talked about habitual

00:30:19.400 | and impulsive behavior circuitry.

00:30:21.820 | There are also dramatic changes in the activity of neurons

00:30:25.860 | that control the release of so-called serotonin.

00:30:28.040 | Serotonin is a neuromodulator.

00:30:30.060 | It changes the activity of neural circuits

00:30:32.860 | and many neural circuits, in particular,

00:30:34.540 | those involved in mood and feelings of wellbeing.

00:30:37.460 | Recently, there's been a lot of interest in serotonin

00:30:39.980 | because of a study that was released

00:30:41.300 | that showed pretty conclusively

00:30:42.840 | that serotonin levels can't really explain depression

00:30:46.700 | and depression-like symptoms.

00:30:48.280 | I want to make it very clear

00:30:49.460 | that although that study did show that serotonin levels

00:30:53.100 | are not necessarily associated with depression,

00:30:56.340 | the study was interpreted by many to mean

00:30:58.580 | that SSRI, selective serotonin reuptake inhibitors,

00:31:01.540 | which have the net effect of increasing serotonin,

00:31:04.540 | these are things like Prozac, et cetera,

00:31:07.200 | that those drugs are somehow not helpful

00:31:10.440 | because they increase serotonin

00:31:13.060 | and serotonin isn't involved in depression.

00:31:15.980 | That logic doesn't really hold together,

00:31:18.320 | so I'm going to use this as an opportunity

00:31:19.720 | to just clarify what really occurred there,

00:31:22.380 | and then we'll talk about how serotonin

00:31:24.020 | relates to alcohol consumption

00:31:25.300 | in things like feeling good and in depression.

00:31:29.100 | The key thing is this,

00:31:30.580 | SSRIs can help alleviate depression.

00:31:34.860 | That's right, SSRIs can help alleviate depression.

00:31:37.820 | They are often not always associated with side effects,

00:31:40.080 | dosage is very important, et cetera,

00:31:42.320 | but they probably support relief from depression

00:31:47.120 | by changing neural circuits,

00:31:48.840 | not necessarily by increasing serotonin itself.

00:31:52.100 | That is, increasing serotonin with these drugs

00:31:54.440 | likely change the neural circuits involved in mood,

00:31:57.500 | allowing people to feel better

00:31:58.820 | through so-called neuroplasticity,

00:32:00.420 | which is the brain's ability to change itself

00:32:02.540 | in response to experience.

00:32:03.860 | So there's a bit of confusion,

00:32:04.900 | and again, I'm using this episode on alcohol

00:32:07.800 | to highlight some of the confusion

00:32:08.980 | because I think it's timely,

00:32:10.300 | because the study just came out

00:32:11.260 | and there's a lot of chatter about this out there,

00:32:13.260 | that when people are depressed,

00:32:15.700 | it's not necessarily because serotonin levels are low.

00:32:18.820 | However, if serotonin levels are increased

00:32:21.160 | with things like Prozac, Zoloft, and other SSRIs,

00:32:24.080 | oftentimes there is, yes, a relief from depression,

00:32:27.800 | but that's probably not

00:32:29.260 | because of restoring serotonin levels per se,

00:32:31.500 | it's probably because serotonin facilitates

00:32:35.380 | the changes in neural circuits that need to occur

00:32:37.540 | in order for people to feel elevated mood, okay?

00:32:40.300 | So again, that's a bit of a tangent and a sigh,

00:32:42.020 | but I do think it's a vital one for people to know about.

00:32:44.700 | Again, if you're thinking about taking SSRIs,

00:32:46.540 | you're currently taking them and you've heard this news,

00:32:48.820 | definitely talk to your doctor.

00:32:50.300 | Again, there is great utility for some of these SSRIs,

00:32:52.660 | and also in conditions like OCD,

00:32:54.740 | they've been shown to be very beneficial,

00:32:56.360 | so we really don't want to throw SSRIs out

00:32:58.580 | as a potentially valuable treatment.

00:33:00.380 | Getting back to the effects of alcohol on serotonin,

00:33:05.000 | it's very clear beyond any doubt

00:33:08.560 | that many of the circuits in the brain

00:33:10.320 | that are involved in mood and feelings of wellbeing

00:33:12.800 | and also sort of self-image in how we see ourselves

00:33:17.120 | employ the neuromodulator serotonin and alcohol

00:33:21.040 | when we ingest it and it's converted into acetaldehyde,

00:33:25.520 | it goes and that acetaldehyde acts as a toxin

00:33:29.640 | at the very synapses,

00:33:31.080 | the connections between the serotonergic neurons

00:33:33.080 | and lots of other neurons.

00:33:34.440 | In other words, when we ingest alcohol,

00:33:36.400 | the toxic effects of alcohol disrupt those mood circuitries

00:33:40.220 | at first making them hyperactive,

00:33:42.860 | that's right, making them hyperactive,

00:33:44.260 | this is why people become really talkative,

00:33:46.260 | people start to feel really good

00:33:47.380 | after a few sips of alcohol, at least most people do,

00:33:50.140 | and then as they can ingest more alcohol

00:33:53.060 | or as that alcohol wears off,

00:33:54.940 | serotonin levels and the activity of those circuits

00:33:57.620 | really starts to drop and that's why people feel less good.

00:34:00.940 | And typically what they do, they go and get another drink

00:34:03.360 | and they attempt to kind of restore that feeling

00:34:05.660 | of wellbeing and mood.

00:34:06.860 | Now, typically what happens

00:34:07.980 | is that as people ingest the third and fourth,

00:34:10.900 | maybe even the fifth drink,

00:34:12.920 | there's an absolute zero chance of them recovering

00:34:15.980 | that energized mood, right?

00:34:17.700 | Most people as they drink more and more

00:34:19.580 | will now start to feel more and more suppressed.

00:34:23.280 | The forebrain is now shutting down quite a lot,

00:34:25.500 | a lot of the motor cortical areas

00:34:27.460 | that control coordinated movement

00:34:29.580 | and deliberate movement start to shut down,

00:34:31.000 | so people start to slur their speech,

00:34:32.980 | people start to shuffle their feet,

00:34:34.740 | people forget their posture,

00:34:36.660 | people start to lean on things,

00:34:38.020 | people start passing out on couches.

00:34:40.140 | There's a great depression,

00:34:41.660 | not depression of the psychiatric depression sort,

00:34:44.960 | but a depression of alertness and arousal

00:34:49.960 | and eventually people will pass out.

00:34:53.020 | Now, I said most people

00:34:54.460 | because there's a subset of people that have gene variants

00:34:57.320 | or who are chronic drinkers

00:35:00.220 | or who are chronic drinkers and have gene variants

00:35:03.500 | that as they ingest the third and fourth and fifth drink,

00:35:07.700 | what happens?

00:35:08.700 | They become more alert, they start talking more,

00:35:11.060 | they feel great, they have all sorts of ideas

00:35:12.800 | about the fun they could have that night

00:35:14.260 | and they're the ones

00:35:15.380 | that if you've ever fallen asleep at a party

00:35:17.660 | for whatever reason or you're getting tired

00:35:19.340 | and you're yawning and looking around the room

00:35:20.620 | and like these people are still drinking and partying

00:35:22.540 | and they're having what seems to be this amazing time,

00:35:25.300 | often not always,

00:35:27.740 | those are the future alcoholics in the room

00:35:31.020 | or those are the people that have a genetic predisposition

00:35:34.700 | for alcoholism or those are the chronic drinkers,

00:35:37.060 | the people who have built up enough of a tolerance

00:35:39.820 | or who have the chemical genetic makeup

00:35:42.500 | such that increasing amounts of alcohol

00:35:44.940 | make them feel better and better and better

00:35:46.800 | and of course they too have a threshold

00:35:49.100 | beyond which their nervous system

00:35:50.680 | will start to get diminished

00:35:51.840 | and they'll pass out and fall over, et cetera,

00:35:55.340 | but that threshold is way, way higher

00:35:57.700 | than it is for most people.

00:35:59.660 | This is important to understand

00:36:01.860 | and it's important to understand

00:36:03.500 | because I think everyone should know

00:36:05.280 | and recognize their own predisposition

00:36:07.580 | and kind of risk in terms of developing alcoholism.

00:36:11.640 | It's also important to understand

00:36:12.860 | because it relates to the phenomenon of blackout.

00:36:15.460 | Many people think that blacking out is passing out,

00:36:18.100 | but blackout drunk is when people drink

00:36:21.340 | and they're talking and doing things,

00:36:22.740 | sometimes sadly or tragically they'll often drive home

00:36:26.980 | or walk home or they'll hop on a bicycle and ride home

00:36:29.240 | or they'll go swimming in the ocean,

00:36:30.360 | all of course very dangerous activities to do

00:36:33.260 | when people are really drunk

00:36:34.900 | or even a little bit drunk in some cases.

00:36:36.660 | So these people will do these sorts of things

00:36:38.960 | and they do them because they have the energy to do them

00:36:41.640 | and they feel good while doing them,

00:36:43.680 | but they are doing them while the activity of neurons

00:36:46.240 | in the hippocampus which is involved in memory formation

00:36:48.880 | are completely shut off

00:36:50.340 | and this is why the next day you tell them,

00:36:54.040 | hey, maybe we should talk about what happened last night.

00:36:56.060 | Like what happened last night?

00:36:57.360 | He said, well, do you remember going to the party?

00:36:58.820 | Yeah, no, it was great.

00:36:59.660 | We did this, we did this and then what?

00:37:01.580 | And it's very clear all of a sudden

00:37:04.140 | that they have no recollection

00:37:05.980 | of all the things they were doing despite being awake.

00:37:08.960 | Now, I wish I could tell you

00:37:09.800 | that there's some sort of blood test or other biomarker,

00:37:12.120 | even a fingerprint test that would allow you

00:37:14.520 | to determine whether or not you have a propensity

00:37:17.360 | to be one of these drinkers

00:37:18.940 | that has a predisposition for alcoholism.

00:37:22.400 | And if you've ever been blackout drunk

00:37:24.420 | and certainly if you've been blackout drunk

00:37:26.280 | more than a few times, you should be quite concerned.

00:37:29.240 | And as we talk more about the more chronic effects

00:37:32.120 | and long lasting effects of alcohol consumption

00:37:34.880 | a little bit later in the episode,

00:37:36.580 | I think it will become clear

00:37:37.500 | as to why you should be concerned.

00:37:39.220 | But in any case, there is something that can tell you

00:37:43.420 | whether or not you might be in that category

00:37:46.220 | versus likely not in that category.

00:37:48.020 | And I alluded to this a couple of times already,

00:37:49.740 | but I want to be really clear

00:37:51.620 | that when people drink, no matter who you are,

00:37:55.980 | initially there's that shutting down

00:37:57.380 | of those prefrontal cortical circuits.

00:37:59.400 | There's a gradual shutting down of the circuits

00:38:01.180 | that control memory,

00:38:02.440 | but then people divide into these two bins.

00:38:04.840 | And these two bins are the people

00:38:06.680 | who after more than a couple of drinks

00:38:09.280 | start to feel sedated.

00:38:11.060 | And the people who after more than a few drinks

00:38:13.200 | do not start to feel sedated.

00:38:15.520 | Now, of course, there's going to be differences

00:38:17.920 | created by how quickly people are drinking,

00:38:20.240 | whether or not they're combining different types of alcohol,

00:38:23.120 | the types of alcohol, et cetera.

00:38:25.020 | But in general, that can predict whether or not

00:38:27.220 | you're somebody who has a predisposition

00:38:28.600 | for alcoholism or not.

00:38:30.240 | One also very interesting finding

00:38:33.600 | is that alcohol changes the relationship

00:38:36.820 | between what's called the hypothalamus

00:38:39.260 | and the pituitary gland and the adrenals.

00:38:41.880 | Now, the hypothalamus is a small collection of neurons

00:38:44.140 | about the size of a large gumball

00:38:45.700 | sits above the roof of your mouth.

00:38:47.100 | And it houses neurons that are responsible

00:38:48.920 | for some incredible aspects of our behavior

00:38:51.300 | and our mindset.

00:38:53.100 | Things like rage, things like sex drive,

00:38:56.340 | things like temperature regulation,

00:38:57.980 | very primitive functions,

00:39:00.060 | including appetite, thirst, et cetera.

00:39:02.560 | Alcohol, because it can go anywhere in the brain,

00:39:04.840 | remember it's water and fat soluble,

00:39:07.040 | has effects on the hypothalamus.

00:39:09.280 | The hypothalamus normally provides very specific signals

00:39:13.660 | to what's called the pituitary gland.

00:39:15.160 | This is a little gland that actually sticks out of the brain,

00:39:18.240 | but it receives instructions from the hypothalamus.

00:39:22.120 | And then the pituitary releases hormones

00:39:24.340 | into the bloodstream that go and talk to your adrenals.

00:39:26.740 | Your adrenal glands sit right above your kidneys

00:39:29.600 | in your lower back.

00:39:30.880 | And the adrenals release, as the name suggests,

00:39:33.760 | adrenaline, also called epinephrine,

00:39:35.300 | and also a molecule called cortisol,

00:39:37.720 | which is involved in the kind of longer-term stress response

00:39:40.640 | has some healthy effects too on the immune system.

00:39:42.560 | Okay, so the hypothalamic-pituitary-adrenal axis,

00:39:45.620 | I know that's a mouthful,

00:39:47.640 | you don't need to remember the names,

00:39:49.120 | but the hypothalamic-pituitary-adrenal axis

00:39:51.560 | maintains your physiological balance

00:39:53.560 | of what you perceive as stressful

00:39:55.160 | and what you don't perceive as stressful.

00:39:57.160 | People who drink regularly,

00:40:00.120 | so this again could be just one or two drinks per night,

00:40:02.740 | or it could be somebody that drinks just on Fridays

00:40:05.280 | or just on Saturdays, or maybe just on the weekend,

00:40:07.720 | two to four drinks.

00:40:09.020 | Well, those people experience changes

00:40:10.740 | in their hypothalamic-pituitary-adrenal axis

00:40:14.000 | that result in more cortisol,

00:40:15.880 | more of this so-called stress hormone

00:40:17.920 | being released at baseline when they are not drinking.

00:40:21.600 | This is really important.

00:40:22.840 | People who drink a bit, and when I say a bit,

00:40:26.000 | I don't mean one or two sips

00:40:27.200 | or even a glass of wine every once in a while.

00:40:29.720 | I mean, again, people that are maybe having

00:40:32.680 | one drink a night with dinner

00:40:34.520 | and maybe on the weekend a few more.

00:40:36.800 | Again, I offer a bunch of different patterns

00:40:38.360 | to explain how it could also be

00:40:41.120 | two or three drinks on Friday

00:40:42.600 | or six drinks only on Saturday.

00:40:44.720 | Well, all of those groups experience increases

00:40:47.200 | in cortisol release from their adrenal glands

00:40:51.120 | when they are not drinking.

00:40:52.440 | And as a consequence, they feel more stressed

00:40:56.240 | and more anxiety when they aren't drinking.

00:40:59.560 | This is a seldom talked about effect of alcohol

00:41:03.120 | because so often we hear about

00:41:04.520 | the immediate effects of alcohol, right?

00:41:06.320 | And we've been talking about some of those effects,

00:41:08.200 | effects like reducing the amount of stress.

00:41:10.420 | I mean, how many times have we heard somebody say,

00:41:12.640 | "Oh, I need a drink."

00:41:13.640 | And then they have a drink and they're like, "Calm down."

00:41:15.600 | Now they can shake off the thoughts about the day's work.

00:41:18.640 | They can start to think about things

00:41:20.000 | in a maybe more grounded or rational way,

00:41:22.260 | or at least they believe that,

00:41:23.400 | or they can somehow just relax themselves.

00:41:26.240 | Well, while that very well may be true

00:41:29.020 | that it can relax them when they are not drinking,

00:41:32.280 | that level of cortisol that's released at baseline

00:41:34.960 | has increased substantially.

00:41:37.180 | Again, this relates to a defined neural circuit

00:41:40.600 | between brain and body,

00:41:41.680 | and it has to do with the ratio of cortisol

00:41:44.220 | to some of the other hormones

00:41:45.880 | involved in the stress response.

00:41:48.000 | We'll provide a reference to the study

00:41:49.540 | that describes how all of this works

00:41:51.200 | for those of you that really want to delve into it.

00:41:53.200 | But let's go back to this issue

00:41:55.480 | of those who are prone to alcoholism

00:41:57.500 | versus those who are not.

00:41:59.000 | Remember, there are people who have genetic variants,

00:42:02.360 | that meaning genes that they inherited from their parents,

00:42:05.780 | that make it more likely that they will become alcoholics.

00:42:08.900 | But there are also people who drink often,

00:42:12.040 | who start to experience this increase in alertness

00:42:14.900 | the longer they drink across the night.

00:42:17.720 | Part of that effect we think is because of changes

00:42:21.200 | in this hypothalamic-pituitary-adrenal axis.

00:42:23.940 | So alcohol is kind of a double hit in this sense.

00:42:27.440 | It's causing changes in our brain circuitry

00:42:29.300 | and neurochemistry that at the time

00:42:31.980 | in which we're inebriated are detrimental,

00:42:34.940 | and it's causing changes in neural circuitry

00:42:37.120 | that persist long past the time

00:42:38.920 | in which we're experiencing the feeling

00:42:40.640 | of being tipsy or drunk.

00:42:42.720 | Now, again, I don't want to demonize alcohol.

00:42:45.000 | I'm not saying, oh, you know,

00:42:46.100 | if you have a glass of wine now and again,

00:42:47.680 | or you drink a beer now and again,

00:42:48.860 | or even have, you know, a mixed drink now and again,

00:42:53.300 | or a shot, that that's necessarily terrible for you.

00:42:55.900 | I certainly do not want that to be the message.

00:42:58.620 | What I'm saying is that

00:43:01.120 | if people are ingesting alcohol chronically,

00:43:03.320 | even if it's not every night,

00:43:05.140 | there are well-recognized changes in neural circuits.

00:43:10.080 | There are well-recognized changes

00:43:11.800 | in neurochemistry within the brain,

00:43:13.920 | and there are well-recognized changes

00:43:16.140 | in the brain-to-body stress system

00:43:19.560 | that generally point in three directions,

00:43:23.100 | increased stress when people are not drinking,

00:43:26.280 | diminished mood and feelings of wellbeing

00:43:30.240 | when people are not drinking,

00:43:32.280 | and as you'll soon learn,

00:43:35.280 | changes in the neural circuitry

00:43:37.440 | that cause people to want to drink even more

00:43:41.100 | in order to get just back to baseline

00:43:43.800 | or the place that they were

00:43:45.240 | in terms of their stress modulation

00:43:46.980 | and in terms of their feelings of mood

00:43:48.220 | before they ever started drinking in the first place.

00:43:51.420 | So again, I don't want to demonize alcohol,

00:43:54.140 | but I do want to emphasize

00:43:55.840 | that there are long-term plastic changes,

00:43:58.280 | meaning changes in neural circuitry and hormone circuitry,

00:44:01.100 | that across a period of several months,

00:44:03.780 | and certainly across a period of years

00:44:05.380 | of the sorts of drinking patterns I described,

00:44:07.500 | which I think for most people

00:44:09.180 | are going to sound like pretty typical, right?

00:44:11.200 | I mean, nothing that I described so far

00:44:12.800 | was about drinking a case a night

00:44:14.300 | or about binging on alcohol

00:44:16.440 | in the way that we often hear about it in the news.

00:44:18.560 | These are pretty common patterns of alcohol consumption.

00:44:21.660 | I mean, all you have to do is board a transatlantic flight

00:44:24.800 | or actually go to an airport on a Sunday afternoon

00:44:27.180 | in a sunny area of the US,

00:44:28.500 | and people are having three, four, five, six beers, et cetera.

00:44:32.640 | Again, personal choice is personal choice.

00:44:34.860 | I'm not telling you what to do,

00:44:36.040 | but it's very clear that those sorts of drinking patterns

00:44:38.700 | are changing neural circuitry

00:44:40.180 | and they're changing hormone circuitry,

00:44:42.100 | and I'd love to be able to tell you

00:44:43.100 | that they're changing them for the better,

00:44:44.320 | but they simply are not.

00:44:46.060 | They're actually changing them for the worse,

00:44:47.580 | and worse is defined as making people

00:44:49.020 | less resilient to stress,

00:44:50.380 | higher levels of baseline stress, and lower mood overall.

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00:46:07.100 | Now, I've been talking a little bit

00:46:08.140 | about genetic predisposition,

00:46:10.560 | but there are a couple of important points

00:46:12.180 | I'd like to make about that.

00:46:13.480 | First of all, what sorts of genes are involved

00:46:16.260 | in setting someone down the path of alcoholism or not?

00:46:20.520 | Well, it should come as no surprise

00:46:22.420 | that the genes that chronic alcohol usage modifies,

00:46:27.380 | they tend to fall primarily in the pathways

00:46:30.940 | related to genetic control over serotonin receptors,

00:46:35.260 | GABA receptors, remember that top-down inhibition

00:46:37.760 | and the involvement of GABA, and no surprise, the HPA,

00:46:41.660 | the hypothalamic-pituitary axis.

00:46:43.740 | All of those, of course, combined with environment,

00:46:46.340 | they combine with patterns of abuse, right?

00:46:48.800 | We know that if you're in a social setting

00:46:50.240 | where a lot of people are drinking,

00:46:51.460 | the likelihood that you're going to drink is much higher.

00:46:54.400 | Social pressures, trauma, right?

00:46:57.740 | Some people will use alcohol to self-medicate

00:46:59.880 | to try and turn off their thinking

00:47:01.240 | or to deal with trauma, et cetera.

00:47:03.440 | So they combine with the environment,

00:47:05.180 | but the genes that are in the serotonin synthesis

00:47:08.520 | and receptor synthesis pathway, GABA and HPA axis

00:47:12.480 | combine with environmental pressures

00:47:14.700 | to give rise to alcohol use disorders.

00:47:18.200 | So there's a fairly coherent picture that we have here, right?

00:47:21.760 | This is not a case where, for instance,

00:47:24.120 | people that have a lot of the enzyme for metabolizing alcohol

00:47:27.060 | which we'll talk about in a minute, alcohol dehydrogenase,

00:47:30.020 | it's not like they are necessarily

00:47:32.160 | the people that become alcoholics.

00:47:33.420 | Whereas certainly in certain cultures,

00:47:35.620 | certain Asian cultures in particular,

00:47:37.840 | there are gene differences that lead them

00:47:40.740 | to have low levels of alcohol dehydrogenase.

00:47:42.640 | There are actually people

00:47:43.480 | who have so little alcohol dehydrogenase

00:47:45.160 | that when they ingest alcohol,

00:47:46.600 | they get very red and they just feel sick.

00:47:48.560 | So if you're somebody that has a sip of alcohol

00:47:50.100 | and you just feel horrible, it makes you feel nauseous,

00:47:52.320 | chances are you have gene variants that create a situation

00:47:56.120 | where you're not making very much alcohol dehydrogenase.

00:47:59.000 | You just simply can't metabolize alcohol.

00:48:01.080 | So you just get a rapid buildup

00:48:02.600 | of the toxic effects of alcohol, the acetaldehyde.

00:48:05.640 | You're not converting it into those empty calories.

00:48:08.400 | But in cultures where you have a lot of genetic variants

00:48:12.600 | and genes expressed in people

00:48:14.480 | where they have a lot of alcohol dehydrogenase,

00:48:16.580 | sure, they can drink more

00:48:18.400 | and they're converting more of that alcohol

00:48:20.160 | from its toxic form to a non-toxic form.

00:48:23.080 | And yes, of course, you will observe more alcoholism

00:48:25.960 | in those communities because they're drinking more.

00:48:28.520 | But I do want to emphasize that the environmental factors

00:48:31.560 | are playing a strong role there too,

00:48:32.960 | because if you can drink more, you're likely to drink more.

00:48:35.360 | If you're somebody that feels sick immediately

00:48:37.360 | from drinking, it's likely that you're not going to engage

00:48:39.180 | in alcohol consumption,

00:48:40.680 | especially if these things are genetically related.

00:48:42.960 | And of course, genes and culture and location in the world

00:48:45.520 | tend to run together.

00:48:47.040 | So do you have the gene for alcoholism?

00:48:50.920 | Well, there isn't one single gene.

00:48:53.040 | Chances are if you have an immediate relative

00:48:55.880 | who's a chronic abuser of alcohol

00:48:58.140 | or several relatives who are chronic abusers of alcohol,

00:49:01.500 | well, that's going to predispose you to be an alcoholic.

00:49:05.140 | But since you don't know which genes you express

00:49:07.360 | unless you do genetic testing and those things are available

00:49:09.920 | but most people aren't doing that,

00:49:11.800 | this assay, if you will, and it's not an assay,

00:49:15.100 | as we say, an assay is a test that you run in the lab

00:49:17.920 | to determine something.

00:49:19.420 | And it's not one that I recommend

00:49:20.720 | that you go drink in order to do.

00:49:22.380 | But if you've noticed that you or somebody else

00:49:24.720 | is somebody who can drink a lot throughout the night

00:49:26.660 | and have increased energy

00:49:27.640 | and can just drink and drink a drink,

00:49:29.900 | and especially if there's blackout episodes,

00:49:32.280 | not remembering things the next day despite being alert

00:49:34.620 | throughout the entire night and so on,

00:49:36.580 | well, then I would be very concerned

00:49:38.540 | that you might actually have a genetic variant

00:49:40.260 | predisposing you to alcoholism.

00:49:42.020 | The other thing that predisposes people to abuse of alcohol

00:49:45.380 | is age.

00:49:47.360 | People who start drinking at younger ages

00:49:51.040 | are greatly predisposed to developing alcohol dependence

00:49:55.760 | regardless of your family history of alcoholism.

00:49:58.500 | Okay, so I'm going to repeat that.

00:49:59.640 | People who start drinking younger

00:50:01.620 | are at great risk for developing alcoholism

00:50:04.580 | even if they don't have alcoholism in their family.

00:50:06.900 | Now, of course, you don't have to be an epidemiologist

00:50:09.580 | to understand that if you grew up in a family of drinkers

00:50:12.300 | and alcohol is everywhere,

00:50:13.860 | and especially if there's peer pressure or lack of oversight,

00:50:16.780 | then there's going to be a higher tendency

00:50:19.260 | or a higher probability, I should say,

00:50:21.080 | that you will start drinking at a younger age.

00:50:23.140 | However, even people that grow up

00:50:25.820 | nowhere near their relatives,

00:50:27.660 | if they start drinking at a young age,

00:50:29.540 | so for instance, at 13 or younger or 14 or 15,

00:50:33.380 | there's a much higher probability

00:50:34.620 | that they're going to develop

00:50:36.060 | a long-lasting dependence on alcohol.

00:50:38.900 | People who take their first sip of alcohol later,

00:50:41.760 | 15, 16, or one would hope even later,

00:50:44.800 | I can say one would hope

00:50:45.740 | 'cause I'm now of that age and generation

00:50:47.840 | where you think about all the things that young people do

00:50:51.260 | and you go, oh gosh, if they only would wait

00:50:53.140 | or if they only would abstain, it's just what happens.

00:50:56.000 | I don't know, there's some neural circuit for that

00:50:57.280 | that I can't explain yet.

00:50:58.540 | But people who, for instance,

00:51:00.680 | drink only once they reach legal age of drinking,

00:51:03.240 | which in the US, I believe in every state is 21 years old,

00:51:06.740 | if they take their first drink at 21,

00:51:08.600 | the probability that they'll go on

00:51:10.040 | to develop full-blown alcohol dependence

00:51:12.240 | or alcohol use disorder, as it's called, AUD, is very low.

00:51:15.660 | Now, a subset of them will

00:51:16.760 | because they have such a strong genetic predisposition

00:51:19.260 | or maybe life circumstances create a pattern

00:51:22.500 | in which they become a chronic drinker.

00:51:24.460 | But I found this very interesting.

00:51:26.260 | Genes matter, but also the age

00:51:29.160 | in which somebody starts drinking really matters.

00:51:32.220 | Now, whether or not that's because there are changes

00:51:34.180 | in neural circuitry as a consequence of that drinking

00:51:37.020 | that make people want to seek out more and more alcohol,

00:51:40.100 | or whether or not there's some other effect,

00:51:42.220 | maybe it's a change in hormones, et cetera,

00:51:44.460 | that predisposes those young drinkers

00:51:46.440 | to become chronic drinkers or even full-blown alcoholics,

00:51:49.540 | certainly developing alcohol use disorder,

00:51:51.920 | there's definition for that, we can talk about it,

00:51:53.620 | it involves the amount of drinking

00:51:55.520 | over a certain period of time, et cetera.

00:51:57.860 | So it's very clear that drinking early in life

00:52:00.460 | creates a propensity for the development

00:52:03.220 | of alcohol use disorder later in life.

00:52:06.460 | And while there is a genetic component

00:52:08.980 | to developing alcohol use disorder,

00:52:10.780 | I find it very interesting

00:52:13.060 | that if people who have those gene variants

00:52:15.580 | delay their onset of drinking,

00:52:18.420 | well, then the probability that they'll develop

00:52:20.080 | full-blown alcohol use disorder drops as well.

00:52:23.080 | So again, it's genes and environments, not an either or,

00:52:25.680 | and there's no single gene for alcoholism.

00:52:28.100 | Well, I promise you, I will also talk about

00:52:30.260 | some of the documented positive effects of alcohol.

00:52:33.620 | Although they are very few and far between,

00:52:36.060 | they do exist.

00:52:37.440 | But before I do that, I would be remiss

00:52:39.640 | if I didn't emphasize some more of the terrible things

00:52:42.680 | that alcohol does and the way that it does it.

00:52:45.300 | And for those of you that enjoy alcohol,

00:52:48.060 | I, again, I really, I like to say I feel guilty

00:52:51.700 | about telling you this because I know how much

00:52:53.700 | some people enjoy a good drink every once in a while,

00:52:55.740 | and I say a good drink because some people

00:52:57.340 | do like the taste of alcohol.

00:52:59.220 | I suppose I lucked out in that I don't really like

00:53:01.060 | the taste of alcohol and that just puts me to sleep,

00:53:03.100 | but I know that people do enjoy it.

00:53:04.740 | And I do want to point out that there is zero evidence

00:53:09.740 | that, you know, provided somebody is of drinking age,

00:53:14.120 | or certainly not in the stage of brain development,

00:53:17.360 | that having one drink or two drinks every now and again,

00:53:20.860 | meaning every three or four weeks or once a month,

00:53:23.940 | that is not going to cause major health concerns

00:53:27.540 | or major health issues for most people.

00:53:30.060 | I suppose if you have zero or very little

00:53:33.100 | alcohol dehydrogenates, it might make you feel sick,

00:53:34.940 | but then you're probably not the kind of person

00:53:36.340 | that's going to be drinking at all.

00:53:38.260 | So again, if you enjoy alcoholic drinks,

00:53:41.080 | I'm not trying to take them away from you by any means,

00:53:46.080 | but you should know what drinking does

00:53:48.400 | if you're consuming it in this kind of typical

00:53:50.820 | chronic pattern, as we can now refer to it,

00:53:52.680 | which is that one or two a night or a few stacked up

00:53:57.580 | on Friday and maybe three or four on Saturday,

00:54:00.380 | this kind of pattern of drinking, which is quite common.

00:54:03.380 | And one of the more serious effects

00:54:04.920 | that we should think about is the impact

00:54:07.080 | on the so-called gut-brain axis,

00:54:08.540 | or for sake of today's discussion,

00:54:10.340 | the gut-liver brain axis.

00:54:12.180 | I don't think the gut-liver brain axis

00:54:13.740 | has ever been discussed on this podcast.

00:54:15.340 | Maybe any podcast, although the moment I say that,

00:54:17.620 | I'm going to, you know, the gut-liver brain axis,

00:54:20.860 | people are going to come after me with,

00:54:22.060 | I suppose, gut, liver, brain, and brains.

00:54:24.440 | In any event, you have a brain, you have a gut,

00:54:29.180 | that gut runs from your throat

00:54:31.320 | down to the end of your intestine.

00:54:36.060 | Your gut and your brain communicate by way of nerve cells,

00:54:39.720 | neurons, and nerve connections,

00:54:41.340 | the vagus nerve in particular,

00:54:43.220 | and by way of chemical signaling.

00:54:45.660 | Your gut also communicates by way of chemical signaling,

00:54:48.340 | and believe it or not, by way of neural signaling

00:54:50.660 | to your liver.

00:54:52.380 | And as we talked about earlier,

00:54:53.820 | the liver is the first site in which alcohol

00:54:56.780 | is broken down and metabolized into its component parts.

00:55:00.220 | The liver is also communicating with the brain

00:55:04.280 | through chemical signaling and neural signaling.

00:55:06.900 | So we have the gut-liver brain axis.

00:55:10.240 | And what you find is that people who ingest alcohol

00:55:14.900 | at any amount are inducing a disruption

00:55:19.020 | in the so-called gut microbiome,

00:55:21.060 | the trillions of little micro bacteria

00:55:23.980 | that take resident in your gut

00:55:25.500 | and that live inside you all the time

00:55:26.820 | and that help support your immune system

00:55:28.300 | and that literally signal by way of electrical signals

00:55:31.920 | and chemical signals to your brain

00:55:33.940 | to increase the release of things like serotonin

00:55:36.480 | and dopamine and regulate your mood

00:55:38.100 | generally in positive ways.

00:55:39.580 | Well, alcohol really disrupts those bacteria.

00:55:41.980 | And this should come as no surprise.

00:55:43.160 | I mean, earlier we talked about this and it's well known.

00:55:45.240 | If you want to sterilize something,

00:55:47.260 | you want to kill the bacteria, you pour alcohol on it.

00:55:50.060 | And I can remember scraping myself or cutting myself.

00:55:53.840 | I was always injuring myself when I was a kid.

00:55:55.820 | And the moment they take out the peroxide,

00:55:58.460 | you're like, "Oh boy, here it comes."

00:55:59.580 | But if there's no peroxide around

00:56:01.360 | and you've got a wound there and you need to clean it out,

00:56:03.380 | yeah, they'll use alcohol,

00:56:04.940 | which I do not recommend by the way.

00:56:06.460 | That's one of the harshest ways to clean a wound.

00:56:08.600 | But for centuries, thousands of years really,

00:56:11.020 | alcohol has been used in order to clean things

00:56:13.920 | and kill bacteria.

00:56:15.620 | So alcohol kills bacteria and it is indiscriminate

00:56:19.700 | with respect to which bacteria it kills.

00:56:22.180 | So when we ingest alcohol and it goes into our gut,

00:56:24.420 | it kills a lot of the healthy gut microbiota.

00:56:27.840 | At the same time, the metabolism of alcohol in the liver,

00:56:30.960 | which you now understand,

00:56:32.120 | that pathway involving NAD, acetylaldehyde and acetate,

00:56:37.120 | that pathway is pro-inflammatory.

00:56:40.800 | So it's increasing the release of inflammatory cytokines,

00:56:43.840 | things like IL-6, et cetera, tumor necrosis factor alpha.

00:56:47.800 | If you'd like to learn more about the immune system,

00:56:49.380 | we did an episode all about the immune system.

00:56:51.460 | You can find it at hubermanlab.com.

00:56:52.940 | It'll teach you all the basics of what are cytokines,

00:56:55.420 | what are mast cells, et cetera.

00:56:57.500 | In any event, all these pro-inflammatory molecules,

00:57:00.800 | those are being released.

00:57:03.920 | You've now got disruption of the gut microbiota.

00:57:07.340 | As a consequence, the lining of the gut is disrupted

00:57:10.500 | and you develop at least transiently leaky gut.

00:57:14.980 | That is bacteria that exists in the gut,

00:57:17.420 | which are bad bacteria,

00:57:18.700 | can now pass out of the gut into the bloodstream.

00:57:20.780 | So you've got a two hit kind of model here.

00:57:23.020 | In biology, we talk about two hit models

00:57:25.420 | that is kind of a one plus one equals four.

00:57:27.900 | And it's generally when you hear two hit,

00:57:29.300 | it's not a good thing.

00:57:30.700 | So you've got bad bacteria from partially broken down food

00:57:35.180 | moving out of the gut.

00:57:36.260 | The good bacteria in the gut have been killed.

00:57:38.340 | You might say, why doesn't the alcohol

00:57:39.740 | kill the bad bacteria in the gut?

00:57:41.980 | Well, the bad bacteria that are from partially digested food

00:57:46.980 | oftentimes escape the gut

00:57:49.380 | before the alcohol can disrupt them.

00:57:52.420 | And so now you've got leaks in the gut wall.

00:57:55.380 | You've got the release of this bad bacteria.

00:57:57.180 | You've got inflammatory cytokines

00:57:59.260 | and other things being released from the liver.

00:58:01.220 | And they are able to get into the brain

00:58:03.780 | through what's called a neuroimmune signaling.

00:58:06.440 | And what's really bizarre in terms of the way

00:58:08.860 | that this manifests in the brain,

00:58:10.740 | I mean, it's not the way I would have done it,

00:58:12.840 | but then again, as I always say,

00:58:14.160 | I wasn't consulted at the design phase.

00:58:16.660 | And anyone who says they did,

00:58:17.680 | you should be very skeptical of them.

00:58:19.520 | The net effect of this is actually to disrupt

00:58:24.000 | the neural circuits that control regulation

00:58:26.380 | of alcohol intake.

00:58:27.720 | And the net effect of that is increased alcohol consumption.

00:58:32.340 | So this is just terrible, right?

00:58:33.760 | I mean, so you're taking in something

00:58:36.000 | that disrupts two systems, the gut microbiota,

00:58:38.760 | and it disrupts in two ways.

00:58:39.820 | It's killing the good gut microbiota,

00:58:41.920 | and it's allowing the bad bacteria

00:58:45.800 | to move from the gut into the bloodstream.

00:58:47.480 | You've also got pro-inflammatory cytokines

00:58:49.680 | coming from the liver, and those converge

00:58:53.280 | or arrive in the brain and create a system

00:58:56.660 | in which the neural circuits cause more drinking.

00:59:00.120 | That's a bad situation.

00:59:01.460 | And this is why people who drink regularly,

00:59:04.000 | even if it's not a ton of alcohol,

00:59:05.920 | again, of the sorts of patterns of drinking

00:59:08.440 | I talked about before, and certainly for those

00:59:10.160 | that are chronic heavy drinkers,

00:59:12.560 | what you end up with is a situation

00:59:14.320 | in which you have inflammation in multiple places

00:59:16.760 | in the brain and body and the desire to drink even more

00:59:20.320 | and to further exacerbate that inflammation

00:59:22.300 | and the gut leakiness.

00:59:24.080 | So this is basically a terrible scenario

00:59:26.240 | for the gut-liver-brain axis.

00:59:28.560 | And it's especially prevalent

00:59:29.880 | in so-called alcohol use disorder.

00:59:31.400 | Again, people that are ingesting somewhere

00:59:32.640 | between 12 and 24 drinks per week.

00:59:34.920 | For those of you that are interested in learning more

00:59:36.720 | about the gut-liver-brain axis

00:59:38.200 | and in particular alcohol use disorder,

00:59:40.080 | I'll provide a link in the show note captions.

00:59:42.240 | And there's a wonderful review on this that details that.

00:59:45.520 | But on the positive side,

00:59:47.440 | it points to the possibility that at least some,

00:59:50.040 | again, at least some of the negative effects

00:59:52.600 | of alcohol consumption,

00:59:53.640 | whether or not you're somebody

00:59:54.760 | who's currently ingesting alcohol

00:59:56.960 | or who used to ingest alcohol

00:59:58.280 | and is trying to so-called repair these systems

01:00:00.400 | of the brain and body,

01:00:01.520 | whether or not replenishing the gut microbiota

01:00:03.940 | is going to be beneficial.

01:00:04.840 | And we know that there are ways to do that.

01:00:07.020 | And we know that there's at least some promise

01:00:09.060 | for the ability for the system to repair itself.

01:00:11.800 | How does one do that?

01:00:13.080 | Well, I've talked before about this on the podcast,

01:00:15.200 | but studies done by colleagues of mine at Stanford,

01:00:17.700 | Justin Sonnenberg, who's been on this podcast as a guest,

01:00:20.040 | an amazing episode all about the gut microbiome

01:00:22.100 | and his collaborator, Chris Garner,

01:00:23.720 | also at Stanford School of Medicine,

01:00:25.800 | have explored not alcoholism,

01:00:28.780 | but what are ways to improve the gut microbiota

01:00:32.840 | in particular to reduce the production

01:00:36.600 | of inflammatory cytokines

01:00:38.460 | and to adjust what's called the inflammatome.

01:00:40.520 | You've heard of the genome and the proteome, et cetera.

01:00:43.080 | Well, the inflammatome is the total array,

01:00:46.880 | or at least the near total array of genes and proteins

01:00:49.960 | that control inflammation.

01:00:51.320 | How can you reduce inflammation

01:00:52.740 | and make that inflammatome healthier?

01:00:55.160 | Well, they've shown that two to four servings

01:00:58.000 | of fermented foods per day,

01:00:59.640 | and here I'm not referring to fermented alcohol,

01:01:01.680 | I'm talking about low sugar fermented foods,

01:01:03.320 | so things like kimchi, sauerkraut, natto,

01:01:06.560 | for those of you that like Japanese food.

01:01:09.940 | There are others, I know, things like kefir,

01:01:12.300 | things like yogurts that have a lot of active bacteria,

01:01:15.600 | again, low sugar varieties of all these things.

01:01:18.100 | Those are terrific at reducing inflammatory markers

01:01:23.040 | and at improving the gut microbiome.

01:01:25.760 | One could imagine that either inoculating oneself

01:01:28.960 | from some of the effects of alcohol,

01:01:30.640 | although I'd prefer that people

01:01:31.560 | just not drink alcohol chronically, frankly,

01:01:34.480 | or if somebody is trying to repair their gut microbiome

01:01:37.160 | because they ingested a lot of alcohol

01:01:39.480 | or because they had a lot of these inflammatory cytokines

01:01:41.600 | for many years or even a short period of time,

01:01:44.400 | regular ingestion of two to four servings

01:01:46.560 | of these fermented foods can be quite beneficial.

01:01:49.820 | Want to make it clear that has not been examined

01:01:53.160 | specifically in the context of alcohol use disorder,

01:01:57.120 | but because a huge component of the negative effects

01:02:00.620 | of alcohol use disorder are based in this gut liver,

01:02:03.340 | brain access and disruption of the gut microbiome

01:02:05.280 | and the inflammatory cytokines,

01:02:07.080 | it stands to reason that things that are well-established

01:02:10.220 | to improve inflammation status,

01:02:12.920 | in other words, reduce inflammation,

01:02:14.580 | such as ingesting two to four servings

01:02:16.200 | of low sugar fermented foods per day,

01:02:18.160 | makes sense in terms of trying to repair

01:02:21.480 | or replenish the system.

01:02:23.240 | One could also imagine taking probiotics or prebiotics.

01:02:25.800 | Certainly that would work as well,

01:02:27.800 | although I've sort of favored the discussion

01:02:29.800 | around fermented foods and replenishment

01:02:31.620 | of the gut microbiome,

01:02:32.940 | mostly because there are more studies

01:02:35.840 | that have examined that in humans

01:02:37.520 | and because of the direct relationship

01:02:39.500 | that's been established between doing that

01:02:41.120 | and reducing negative markers within the inflammatome.

01:02:44.280 | And I should mention along the lines of repair and recovery,

01:02:47.160 | I put out a question on Twitter the other day.

01:02:49.240 | I said, "What do you want to know about alcohol?"

01:02:51.140 | I got more than a thousand questions.

01:02:53.240 | And we'll take some more of those questions

01:02:54.520 | a little later in the episode.

01:02:55.480 | But one of the things I noticed

01:02:56.480 | is that many of the questions, hundreds in fact,

01:03:00.000 | related to the question of,

01:03:02.360 | "Well, if I drank a lot previously, am I doomed?

01:03:05.760 | Can I reverse the negative effects?"

01:03:07.400 | Or, "I'm trying to drink less

01:03:09.560 | and I'm trying to improve my health as I do that.

01:03:11.860 | What should I do?"

01:03:12.700 | Well, certainly focusing a bit on the gut microbiome

01:03:16.100 | ought to be useful.

01:03:17.520 | The other thing that I should mention is

01:03:19.220 | as people wean themselves off alcohol,

01:03:21.040 | even if they're not full-blown alcoholics

01:03:23.300 | or have alcohol use disorder,

01:03:25.000 | they should understand that that increase in cortisol

01:03:28.880 | that we talked about earlier

01:03:29.880 | that leads to lower stress threshold

01:03:32.020 | and greater feelings of anxiety and stress,

01:03:34.580 | that's going to be present

01:03:36.940 | and it's going to take some time to dissipate.

01:03:39.280 | So for some people, it might even just be helpful to realize

01:03:42.600 | that as you try and wean yourself off alcohol

01:03:45.520 | or maybe even go cold turkey,

01:03:47.220 | that increased anxiety and feelings of stress

01:03:51.360 | should be expected.

01:03:52.620 | And in that case, I would point you to an episode

01:03:54.400 | that we did on master stress.

01:03:55.920 | You can find that again at hubermanlab.com.

01:03:57.720 | It's got a ton of behavioral,

01:03:58.800 | nutritional, supplementation-based, exercise-based,

01:04:01.600 | I suppose exercise is behavioral.

01:04:03.320 | But a lot of tools, you can navigate to those easily

01:04:05.800 | 'cause we have timestamps.

01:04:06.720 | You can go right to the topic of interest.

01:04:08.340 | Those tools are going to be very useful

01:04:09.720 | in trying to clamp or control your stress.

01:04:12.260 | And the point here is just that some increase in stress

01:04:15.340 | should be expected.

01:04:16.980 | And it should be expected

01:04:18.100 | because of that increase in cortisol that occurs

01:04:20.120 | with even low-level consumption,

01:04:22.320 | yet chronic alcohol consumption.

01:04:24.380 | Now I'd like to talk about a fairly common phenomenon,

01:04:27.600 | which is post-alcohol consumption malaise,

01:04:31.420 | also referred to as hangover.

01:04:34.000 | Hangover is a constellation of effects

01:04:37.040 | ranging from headache to nausea

01:04:40.120 | to what's sometimes called a anxiety,

01:04:42.520 | which is anxiety that follows a day of drinking.

01:04:45.780 | Hangxiety, I think we can understand physiologically

01:04:50.200 | if we think about that process of alcohol intake

01:04:54.860 | increasing the amount of cortisol

01:04:56.920 | and the ratio of cortisol to some other stress hormones.

01:05:00.540 | That well explains why some people wake up the day after

01:05:04.200 | or even the day after a night drinking

01:05:08.740 | and feel anxious and not well and stressed

01:05:11.420 | for reasons they don't understand.

01:05:13.200 | So if you're somebody who experiences hangxiety,

01:05:17.260 | then again, I refer you to the master stress episode

01:05:20.460 | that we put out some time ago,

01:05:22.340 | and you can find that at hubermanlab.com.

01:05:24.280 | Tools to deal with anxiety,

01:05:25.500 | tools to deal with stress ranging again from behavioral

01:05:27.860 | to nutritional, supplement-based, et cetera.

01:05:30.840 | That, of course, is not justification for going out

01:05:33.760 | and drinking so much

01:05:34.640 | that you get hangxiety-induced hangover.

01:05:38.000 | But for those of you that are experiencing

01:05:39.920 | post-alcohol consumption hangxiety, as it were,

01:05:43.380 | that could be a useful resource

01:05:44.780 | because I certainly don't want anyone

01:05:46.380 | experiencing uncomfortable amounts of anxiety,

01:05:49.120 | and there are great tools and resources for that.

01:05:51.540 | Now, the other aspects of hangover,

01:05:54.100 | such as the stomach ache or headache

01:05:58.340 | or feelings of malaise or fogginess,

01:06:01.140 | those can be related to a number of different things

01:06:02.780 | and probably are related to a number of different things.

01:06:05.140 | First of all, the sleep that one gets after even just one,

01:06:10.020 | yes, even just one glass of wine or a beer

01:06:13.940 | is not the same sleep that you get

01:06:15.660 | when you don't have alcohol circulating in your system.

01:06:18.260 | And not trying to be a downer here,

01:06:19.620 | but this was discussed in the Huberman Lab podcast episode

01:06:22.660 | where I had Dr. Matthew Walker from UC Berkeley on,

01:06:26.100 | and of course, Dr. Walker is a world expert in sleep,

01:06:29.820 | runs one of the preeminent laboratories

01:06:31.540 | studying sleep and its effects,

01:06:33.500 | wrote the incredible book, "Why We Sleep," and so on.

01:06:36.540 | Dr. Walker told me, and it certainly is supported

01:06:40.260 | by lots and lots of quality peer-reviewed studies

01:06:43.300 | in animals and in humans,

01:06:45.020 | that when alcohol is present in the brain and bloodstream,

01:06:48.400 | that the architecture of sleep is disrupted.

01:06:50.260 | Slow wave sleep, deep sleep, and rapid eye movement sleep,

01:06:53.140 | all of which are essential

01:06:54.060 | for getting a restorative night's sleep are all disrupted.

01:06:56.260 | So for those of you that are drinking a glass or two of wine

01:06:59.680 | or having a hard liquor drink or a beer

01:07:03.700 | in order to fall asleep,

01:07:05.360 | the sleep you're getting is simply not high quality sleep

01:07:07.900 | or certainly not as high quality as the sleep

01:07:09.700 | you'd be getting if you did not have alcohol in your system.

01:07:12.940 | Of course, when we're talking about hangover,

01:07:14.740 | we're talking generally about the consumption

01:07:17.100 | of more than just one or two drinks.

01:07:19.540 | Of course, for some people,

01:07:20.580 | one or two drinks is probably sufficient to induce hangover,

01:07:23.200 | but for most people, it's going to be having three or four,

01:07:25.900 | exceeding their typical limit, as it's called.

01:07:28.580 | Again, not the legal limit, that's a whole other business.

01:07:31.660 | But when one ingests too much alcohol for them,

01:07:35.160 | one of the reasons they feel terrible the next day

01:07:39.300 | is because their sleep isn't really good sleep.

01:07:41.340 | In fact, it's not even sleep,

01:07:42.860 | it's often considered pseudo-sleep,

01:07:44.820 | or at least that's what it's called

01:07:45.740 | in the sleep science field,

01:07:47.060 | because people are in kind of a low-level hypnotic

01:07:50.000 | kind of trance, it's not real sleep,

01:07:51.540 | there are multiple bouts of waking up,

01:07:52.940 | they may not even realize they're waking up multiple times.

01:07:55.860 | Okay, so there's the sleep-induced effects.

01:07:57.620 | Then there are the disrupted gut microbiome effects,

01:08:01.820 | some of which we talked about earlier,

01:08:03.140 | so now you understand the mechanism

01:08:04.980 | of alcohol destroying good, healthy gut microbiota,

01:08:09.520 | which then leads to leaky gut and things of that sort.

01:08:12.240 | But one could imagine, again, could imagine,

01:08:14.980 | and there is some evidence starting to support this,

01:08:17.700 | that again, ingesting low-sugar fermented foods,

01:08:21.480 | or maybe in prebiotic or probiotics

01:08:23.300 | to support the gut microbiome might assist

01:08:25.500 | in some of the gut-related malaise associated with hangover.

01:08:30.180 | In other words, get those gut microbiota healthy again

01:08:33.420 | as quickly as possible, or maybe even before you drink,

01:08:36.060 | have those gut microbiota healthy,

01:08:37.320 | I would hope that you would do that.

01:08:38.160 | I think everybody should be doing something

01:08:39.540 | to support their gut microbiome,

01:08:40.920 | whether or not it's the ingestion

01:08:41.940 | of low-sugar fermented foods daily,

01:08:43.780 | or at least on a regular basis,

01:08:45.540 | or ingestion of probiotic or prebiotic,

01:08:47.940 | the gut microbiome is so important

01:08:49.440 | for so many different things.

01:08:51.100 | In terms of hangover and headache,

01:08:54.980 | we know that that's caused by vasoconstriction,

01:08:58.020 | the constriction of blood vessels

01:08:59.500 | that tends to occur as a rebound after a night of drinking.

01:09:02.900 | Alcohol can act as a vasodilator,

01:09:04.780 | it can dilate the blood vessels.

01:09:06.020 | Part of that is associated with the increase

01:09:09.300 | in so-called parasympathetic tone.

01:09:11.300 | We have an autonomic nervous system,

01:09:12.760 | it's got a sympathetic component.

01:09:14.900 | These are neurons that make us more alert,

01:09:17.160 | and if they're very active, they make us very stressed.

01:09:19.540 | There's also the parasympathetic aspect

01:09:22.620 | of the autonomic nervous system.

01:09:23.660 | This is all just fancy geek speak

01:09:25.140 | for the parts of your brain and body,

01:09:26.920 | the nerve cells that make you very relaxed.

01:09:28.580 | When you're very relaxed, there tends to be vasodilation.

01:09:32.700 | It allows for more movement of blood and other things

01:09:35.620 | through the bloodstream,

01:09:37.420 | and alcohol tends to induce some vasodilation,

01:09:40.640 | at least in some of the capillary beds.

01:09:42.340 | And then when the alcohol wears off,

01:09:44.320 | there's vasoconstriction, and people get brutal headaches.

01:09:48.080 | That's why some people will take aspirin or Tylenol

01:09:50.940 | or Advil or things like that,

01:09:53.440 | the sort of non-steroid anti-inflammatories.

01:09:55.860 | I should mention there's a lot of literature coming out

01:09:58.560 | that some of these non-steroid anti-inflammatory drugs

01:10:02.300 | are not good for us for a number of different reasons,

01:10:04.480 | the way they impact the liver,

01:10:06.320 | the way they impact the immune system,

01:10:08.300 | and no surprise, the way they impact the gut microbiome.

01:10:11.860 | So I'm not one to tell you

01:10:13.400 | what medications to take or not take,

01:10:15.360 | but you certainly would want to do a quick web search

01:10:17.740 | of effects of non-steroid anti-inflammatories and aspirin

01:10:22.740 | before you start taking those,

01:10:24.920 | or stop taking those for that matter.

01:10:27.620 | Generally, they will alleviate headache,

01:10:29.120 | but they can often have other issues,

01:10:30.900 | including liver issues.

01:10:31.820 | And keep in mind, the night after drinking,

01:10:33.820 | your liver has already taken a beating

01:10:35.980 | because of the need of the liver

01:10:38.020 | to convert alcohol from acetaldehyde into acetate,

01:10:42.820 | which is now a pathway that you well understand.

01:10:45.020 | So I'm not certain,

01:10:46.660 | and in fact, I believe it's not the greatest idea

01:10:48.540 | to burden your liver further through the use of things

01:10:52.500 | that are going to cause it to have to work harder

01:10:54.940 | and metabolize things

01:10:56.020 | if the goal is simply to alleviate a headache.

01:10:58.680 | There's a lot of kind of lore,

01:11:01.100 | old school lore about how to relieve a hangover.

01:11:03.060 | We already talked about how eating food won't do that,

01:11:06.060 | but eating food will prevent the rapid absorption

01:11:09.620 | of even more alcohol into the bloodstream.

01:11:11.880 | There's the lore that one should simply ingest more alcohol.

01:11:15.660 | What terrible advice that is.

01:11:17.260 | That's just going to delay an even worse hangover.

01:11:19.460 | However, I'd be remiss if I didn't say

01:11:22.220 | that the reason that that myth came to be,

01:11:25.420 | or that I should say that truth came to be,

01:11:28.380 | because indeed ingesting more alcohol

01:11:31.120 | will alleviate a hangover,

01:11:32.640 | but then a worse hangover will show up.

01:11:34.700 | The reason that came to be is because ingestion of more

01:11:36.980 | alcohol will cause those constricted vessels

01:11:39.760 | that are giving the headache to dilate again.

01:11:41.980 | But of course, ingesting more alcohol to relieve a hangover

01:11:44.460 | is simply a bad idea.

01:11:45.960 | Just don't do it.

01:11:46.800 | I think this is called the hair of the dog approach.

01:11:48.680 | Maybe someone can put in the show note captions on YouTube

01:11:51.220 | why it's called the hair of the dog.

01:11:52.980 | I can come up with a few ideas,

01:11:55.320 | but they're not going to be very good ones.

01:11:58.420 | And some of them would probably even be outright ridiculous.

01:12:01.940 | So do not ingest more alcohol simply to try

01:12:04.600 | and recover from a hangover.

01:12:06.580 | I know many people have tried that one before,

01:12:08.720 | but that's a terrible idea.

01:12:10.520 | Now, one thing that you'll also hear out there

01:12:12.080 | is that deliberate cold exposure,

01:12:14.180 | for instance, taking a cold shower might relieve hangover.

01:12:17.200 | I find this one particularly interesting

01:12:18.720 | because we've done episodes on the benefits

01:12:20.900 | of deliberate cold exposure.

01:12:21.840 | We have an entire episode about that.

01:12:23.800 | You can find it again, human lab.com.

01:12:26.360 | There are direct links to some of the tools

01:12:28.040 | related to deliberate cold exposure.

01:12:29.840 | And we have an entire newsletter

01:12:32.680 | on deliberate cold exposure protocols.

01:12:34.460 | You can find on human lab.com

01:12:35.820 | go to our neural network newsletter.

01:12:37.680 | So those of you that are interested in ice baths

01:12:39.680 | and cold showers and ways to leverage those,

01:12:42.140 | you can find that there.

01:12:43.440 | What you won't find there is a description

01:12:45.200 | of how to use deliberate cold exposure

01:12:46.600 | for sake of treating hangover.

01:12:48.100 | But here I went into the literature

01:12:49.440 | and I found something kind of interesting.

01:12:51.080 | There is some evidence that increasing levels of epinephrine

01:12:54.720 | in the bloodstream can actually help with alcohol clearance.

01:12:58.680 | That was very surprising to me.

01:12:59.920 | And I want to point out,

01:13:00.760 | this is not a large and robust literature,

01:13:03.000 | but there's some evidence pointing to the fact

01:13:04.880 | that when levels of epinephrine, adrenaline,

01:13:06.900 | are raised in the brain and bloodstream,

01:13:08.920 | that some of the components of alcohol metabolism

01:13:11.120 | can be accelerated

01:13:12.140 | and some of the inebriating effects of alcohol

01:13:14.980 | can be reduced.

01:13:15.820 | So maybe this old school lore of taking a cold shower

01:13:18.320 | actually has something to it.

01:13:19.660 | So in thinking about the use of deliberate cold exposure

01:13:22.000 | in order to reduce the effects of hangover

01:13:24.560 | or to more rapidly clear alcohol

01:13:28.040 | from the brain and bloodstream,

01:13:29.740 | I want to be very clear

01:13:31.080 | and I want to emphasize your safety.

01:13:34.520 | The way to do that is to understand

01:13:36.400 | that alcohol lowers core body temperature, okay?

01:13:39.800 | It can make people slightly hypothermic.

01:13:42.540 | It's going to drop core body temperature.

01:13:44.960 | So if you were inebriated

01:13:47.440 | and you went and got into a body of water, right?

01:13:50.000 | A pool or a lake or something,

01:13:52.000 | first of all, that's extremely dangerous to do

01:13:54.240 | while you're inebriated, right?

01:13:55.540 | People drown all the time.

01:13:56.760 | People drown, they die as a consequence of doing that.

01:13:59.120 | So please don't do that.

01:14:00.940 | But also if it's very cold water,

01:14:03.040 | your core body temperature is going to drop even further.

01:14:05.740 | Now, if you've heard the episodes

01:14:07.120 | that I've done on deliberate cold exposure,

01:14:09.660 | previously I've talked about how normally

01:14:12.080 | when people are not ingesting alcohol,

01:14:14.300 | they get into an ice bath or a cold shower

01:14:16.040 | and their body temperature initially dips,

01:14:17.820 | but then it rebounds and increases.

01:14:19.420 | That's a process that's going to occur

01:14:20.920 | when people do not have alcohol in their system.

01:14:23.560 | When you have alcohol in your system,

01:14:24.980 | one of the reasons that you become hypothermic

01:14:27.660 | is because there's a disruption

01:14:29.180 | in those hypothalamic brain areas,

01:14:30.620 | in particular the brain area

01:14:31.640 | called the medial preoptic area

01:14:33.440 | that regulates core body temperature.

01:14:35.400 | So it's not so much that alcohol makes you cold,

01:14:37.980 | it's that alcohol disrupts the central command centers

01:14:41.480 | of the brain that control temperature regulation

01:14:43.760 | and that leads you to be slightly hypothermic.

01:14:46.740 | So if you then go get into a very cold lake

01:14:49.160 | or you get into even a cold shower or an ice bath,

01:14:52.540 | there's the possibility of you going very, very far down

01:14:56.320 | the ladder into very hypothermic territory

01:14:59.200 | and that can be very dangerous.

01:15:00.740 | Now, in terms of dealing with hangover

01:15:02.380 | when the alcohol has been largely cleared from your system,

01:15:05.200 | well, that's where some of this kind of old lore

01:15:07.940 | combines with some of the modern science and says,

01:15:10.600 | well, if you can spike adrenaline

01:15:12.180 | and certainly getting into an ice bath

01:15:15.220 | or getting into a cold shower

01:15:16.860 | or any kind of cold body of water,

01:15:19.120 | provided you can do that safely,

01:15:20.340 | that will sharply increase your adrenaline

01:15:22.660 | and I should say your dopamine, that's been shown

01:15:24.740 | and we've talked about this on the podcast before,

01:15:26.380 | you get these long extended increases, several hours

01:15:29.400 | of increases in dopamine from deliberate cold exposure.

01:15:31.780 | It's well-documented in humans, by the way.

01:15:34.180 | So one could imagine using deliberate cold exposure

01:15:37.920 | as a way to accelerate the recovery from hangover.

01:15:41.880 | Provided that's done safely,

01:15:43.260 | I think there's no reason to not explore that

01:15:45.500 | and if you're wondering what safely is

01:15:47.860 | and what temperatures to use,

01:15:49.260 | please check out the episode on deliberate cold exposure.

01:15:52.540 | Cold showers therefore might actually be one way

01:15:55.860 | to at least partially relieve hangover.

01:15:57.640 | Certainly the science from various places

01:16:00.740 | in the literature converge to say that,

01:16:02.300 | but again, be careful, please, please, please be careful

01:16:05.660 | not to get into cold water when you are inebriated.

01:16:09.180 | It's absolutely dangerous for all the obvious reasons

01:16:12.180 | and it's dangerous also for the non-obvious reasons,

01:16:14.700 | not the least of which is the dramatic decreases

01:16:17.780 | in core body temperature

01:16:18.980 | that can make you dangerously hypothermic.

01:16:21.380 | Now, how would you go about using deliberate cold exposure

01:16:23.660 | to accelerate recovery from hangover?

01:16:25.520 | Well, there I would look to the kind of standard protocols

01:16:28.400 | of one to three minutes or maybe even six minutes

01:16:30.520 | if you can tolerate or if you're really cold adapted,

01:16:33.280 | maybe you do seven or 10 minutes in a cold shower,

01:16:35.740 | although that could be a lot.

01:16:36.640 | Most people are going to experience a sharp increase

01:16:40.300 | in epinephrine and adrenaline

01:16:41.620 | and a long lasting increase in dopamine

01:16:44.220 | from one to three minutes of deliberate cold exposure,

01:16:47.460 | ideally done immersion up to the neck,

01:16:49.180 | again, do this safely, please, please, please,

01:16:51.280 | or a cold shower where you're getting under the shower

01:16:53.220 | as much as possible.

01:16:54.040 | How cold, well, that's going to vary person to person.

01:16:56.700 | I suggest making it as cold as is uncomfortable

01:16:59.500 | such that you really want to get out,

01:17:00.880 | but then you know you can stay in safely

01:17:02.260 | without, for instance, giving yourself a heart attack

01:17:03.780 | because if the water is really, really cold,

01:17:05.420 | of course you can give yourself a heart attack.

01:17:06.740 | Most showers won't go that cold,

01:17:08.380 | although probably some will.

01:17:10.380 | Again, please use caution, spike your adrenaline,

01:17:12.780 | spike your dopamine with deliberate cold exposure safely.

01:17:15.860 | Other components of hangover that could be good targets

01:17:18.200 | for trying to alleviate hangover,

01:17:19.940 | and here I hope you are getting the picture

01:17:21.980 | because it is accurate to say that hangover

01:17:25.600 | is a multifaceted phenomenon.

01:17:27.740 | It's not like one molecule and one receptor.

01:17:29.540 | It's a bunch of things happening in the brain and body,

01:17:31.800 | but is the dehydration associated with alcohol.

01:17:34.860 | Alcohol is a diuretic for multiple reasons.

01:17:37.800 | It causes people to excrete not only water, but also sodium.

01:17:41.860 | Sodium is an electrolyte critical

01:17:43.480 | for the function of neurons.

01:17:44.660 | So making sure that you have enough sodium, potassium,

01:17:47.040 | and magnesium, so-called electrolytes,

01:17:49.460 | is going to be important for proper brain function,

01:17:52.980 | bodily organ function.

01:17:54.580 | Even for people that have just had one or two drinks

01:17:56.620 | the night before, it's likely that your electrolyte balance

01:17:59.900 | and your fluid balance is going to be disrupted,

01:18:02.340 | and that's because alcohol

01:18:03.660 | also disrupts the so-called vasopressin pathway.

01:18:06.340 | I talked a lot about vasopressin

01:18:08.500 | and the way that it interacts with

01:18:10.980 | and controls different aspects of water retention

01:18:13.620 | and water release from the body in the form of urine

01:18:16.180 | in the episode on salt.

01:18:18.180 | So again, I'm referring to Hubermanlab.com

01:18:21.760 | as the site where you can find that episode

01:18:23.220 | on salt balance and ways to restore electrolyte balance.

01:18:26.100 | Having your electrolytes at the proper levels

01:18:29.740 | before you drink is ideal.

01:18:31.340 | Some people will say for every glass of alcohol

01:18:34.180 | that you drink, you should drink one glass of water.

01:18:36.860 | I would say better would be two glasses of water

01:18:40.060 | given the dehydrating effects of alcohol,

01:18:42.020 | and even better would be water with electrolytes.

01:18:44.540 | That certainly would set you up

01:18:46.020 | for a better day the next day.

01:18:47.840 | And if you don't manage to do that,

01:18:50.080 | 'cause I suppose it's kind of geeky

01:18:51.200 | walking around with electrolyte packets

01:18:53.420 | out at the bar or whatnot,

01:18:55.060 | although, you know, geeky in my book is a good thing,

01:18:59.080 | the next day you could take some electrolytes upon waking,

01:19:02.540 | maybe even some before you go to sleep

01:19:04.620 | at the night of drinking.

01:19:05.940 | So hangovers made worse by disturbed sleep,

01:19:09.000 | made worse by disrupted gut microbiome,

01:19:10.860 | made worse by disrupted electrolytes,

01:19:13.020 | made worse by the depletion of epinephrine and dopamine.

01:19:16.420 | That's why replenishing the microbiome with fermented foods,

01:19:19.800 | low sugar fermented foods that is,

01:19:21.680 | that's why using safe deliberate cold exposure

01:19:25.540 | for spiking adrenaline and for increasing dopamine,

01:19:29.940 | and that's why consuming electrolytes

01:19:32.600 | are all going to be beneficial.

01:19:34.760 | The folks over at examine.com, a website that I really like

01:19:38.440 | because it just has so much useful information,

01:19:41.100 | have assembled a list of things that have been proposed,

01:19:45.320 | purported to improve, or I should say,

01:19:48.820 | to remove the effects of hangover.

01:19:51.620 | And as they point out, and I would like to point out

01:19:54.320 | over there, there isn't a lot of quality science

01:19:56.900 | to support the idea that any one compound

01:19:59.760 | can eliminate hangover.

01:20:01.100 | And that's probably because hangover, again,

01:20:03.140 | arises from multiple organs and tissues and systems

01:20:05.940 | in both the brain and body.

01:20:07.380 | Nonetheless, they have a terrific list over there of things,

01:20:10.720 | everything from Japanese pear fruit juice

01:20:14.020 | has been proposed to do this,

01:20:15.280 | to some other really esoteric things,

01:20:17.560 | even things like yohimbine.

01:20:20.800 | Frankly, when I look at the literature there and elsewhere,

01:20:25.520 | one simply cannot find the magic substance, the one herb,

01:20:30.100 | the one potion that can wipe away hangover.

01:20:33.820 | Getting rid of hangover is going to be best solved

01:20:37.380 | by doing a collection of a small number

01:20:40.060 | of very powerful things,

01:20:41.760 | of which I've already listed off a few.

01:20:44.400 | However, there are some additional things

01:20:46.040 | that one can do for relieving hangover.

01:20:48.460 | And one of them is to be very thoughtful

01:20:51.820 | about what sorts of alcohol one consumes.

01:20:54.380 | So I find this interesting.

01:20:56.100 | There have actually been studies of which types of alcohol

01:21:00.620 | lead to the greatest hangovers.

01:21:02.180 | There's actually a lot of legend and lore about this as well.

01:21:06.220 | Some people have said, for instance,

01:21:07.560 | that drinks that have a high sugar content

01:21:10.180 | lead to greater hangovers.

01:21:12.320 | Turns out that's not the case,

01:21:13.640 | or at least that's not what the science points to.

01:21:15.700 | If you look at the expected hangover severity,

01:21:18.780 | what you find is that at the bottom end of the scale,

01:21:21.960 | there's a drink that I'm not going to tell you for the moment

01:21:25.820 | but what you find is that near it is, for instance, beer.

01:21:28.940 | The consumption of beer,

01:21:31.200 | provided it is not overconsumption, right?

01:21:33.620 | It's not far beyond the tolerance of the individual.

01:21:36.860 | So it's one or two beers,

01:21:38.300 | is less likely to cause a hangover than, say, whiskey.

01:21:42.640 | And a glass of whiskey,

01:21:44.260 | or I should not as much whiskey as beer, of course,

01:21:46.900 | but a glass of whiskey, for instance,

01:21:48.460 | is more likely to cause hangover than gin, as it turns out.

01:21:53.100 | Again, this is what's fallen out of the data.

01:21:56.340 | And yet a glass of rum or red wine

01:22:00.060 | is more likely to cause a hangover

01:22:02.080 | than any of the other things I've mentioned so far.

01:22:04.420 | At the top, top, top of the list of drinks

01:22:06.540 | that induce hangover is brandy.

01:22:08.980 | And one could then say,

01:22:10.800 | well, doesn't brandy have a lot of sugar?

01:22:12.620 | Maybe it's the sugar that's causing hangovers.

01:22:14.420 | And this is something that's been, again,

01:22:16.000 | discussed over and over that people say,

01:22:17.500 | oh, it's the high sugar drinks that cause hangover.

01:22:19.860 | It turns out, however, that when one looks at drinks,

01:22:24.340 | alcoholic drinks and sugar content and hangover,

01:22:26.900 | at the very bottom of the list is,

01:22:29.220 | gosh, this makes me cringe just to think about,

01:22:32.000 | is ethanol diluted in orange juice?

01:22:35.380 | Oh, I can't believe people actually drink this,

01:22:37.580 | but ethanol diluted in orange juice.

01:22:39.260 | So this is not vodka and orange juice, okay?

01:22:41.380 | Vodka was third on the list

01:22:42.900 | from the bottom of drinks that induce hangover.

01:22:45.320 | Again, this is within amounts

01:22:47.420 | that are comfortable for the person to drink,

01:22:50.220 | that they have enough experience with,

01:22:52.040 | or that they have the body weight to tolerate

01:22:53.640 | without getting very, very drunk.

01:22:55.540 | So the point is that if it were sugar

01:22:58.660 | that's causing hangover,

01:22:59.700 | well, then the ethanol dilute in orange juice

01:23:02.940 | would probably be at the top of the list

01:23:04.680 | in terms of inducing hangover.

01:23:06.260 | But it's not, it's at the bottom of the list.

01:23:07.780 | And brandy is at the top of the list.

01:23:09.940 | So what you find is that what scales

01:23:12.940 | from ethanol diluted in orange juice

01:23:15.360 | to beer to vodka to gin,

01:23:16.660 | here I'm ascending the hierarchy of things

01:23:18.520 | that cause hangover, gin, white wine, whiskey, rum, red wine,

01:23:22.160 | and then brandy at the peak,

01:23:24.100 | it's sort of the world heavyweight champion

01:23:26.660 | of hangover-inducing drinks.

01:23:29.140 | Well, what's increasing are congeners within those drinks.

01:23:34.300 | Congeners are things like nitrites and other substances

01:23:37.900 | that give alcohol its distinctive flavor

01:23:41.720 | and that also lead to some of the

01:23:44.660 | inebriating effects of alcohol.

01:23:46.880 | Now, then you ask, okay, well,

01:23:48.040 | what is it that these congeners are doing

01:23:50.820 | and what are these nitrites doing?

01:23:52.160 | And guess what?

01:23:53.520 | While they do have effects on the brain

01:23:55.120 | and on other tissues,

01:23:57.060 | their main effects are to disrupt the gut microbiome.

01:24:00.840 | So what this points to, again,

01:24:03.400 | is that having a healthy gut microbiome

01:24:05.860 | and perhaps ensuring that you bolster your gut microbiome

01:24:10.620 | the day after drinking is going to be especially important

01:24:14.500 | for warding off hangover,

01:24:16.620 | at least reducing the effects of hangover

01:24:19.400 | or the symptoms of hangover or both.

01:24:21.580 | I would love to see a study on this.

01:24:24.100 | I could imagine designing the study myself,

01:24:25.960 | although this isn't really the sorts of things

01:24:27.620 | my laboratory does,

01:24:29.120 | but you can imagine some people getting probiotic

01:24:31.780 | and prebiotic, some regularly,

01:24:33.900 | some just after drinking or low sugar fermented foods

01:24:37.200 | and see what the effects are

01:24:38.220 | in terms of subjective effects of hangover,

01:24:40.620 | but also some physiological measures.

01:24:42.480 | I think that way to think about hangover overall

01:24:45.780 | is that, again, it represents a multifaceted,

01:24:50.120 | multi-organ, multi-tissue phenomenon.

01:24:53.980 | And the best way to deal with it

01:24:55.580 | is as a multi-cell, multi-tissue, multi-chemical phenomenon.

01:24:59.820 | And before I listed off some of the things

01:25:01.360 | that one could do in order to adjust hangover,

01:25:03.980 | again, the one that comes out at the top of that list,

01:25:08.660 | I believe, at least based on my read of the data,

01:25:10.900 | is to support the gut microbiome

01:25:13.420 | and certainly not to ingest more alcohol.

01:25:16.580 | And I suppose if we were to get really honest

01:25:19.100 | with one another and ask,

01:25:21.020 | what's the best way to avoid a hangover?

01:25:23.360 | It would be to not drink in the first place.

01:25:25.620 | So we've covered the major effects of alcohol

01:25:28.160 | that lead to this state that we call drunkenness

01:25:31.700 | or inebriation.

01:25:33.300 | Again, there's a range there.

01:25:34.460 | It can be tipsy, people can be blackout drunk,

01:25:37.180 | people can be passed out drunk.

01:25:39.300 | We've also talked about hangover

01:25:42.000 | and the fact that it's a multifaceted phenomenon

01:25:44.500 | and recovery from hangover

01:25:46.140 | involves a multifaceted approach.

01:25:48.800 | Next, I want to talk about tolerance.

01:25:51.700 | Tolerance to alcohol is a very interesting phenomenon.

01:25:54.440 | It has roots mainly in the brain and in brain systems.

01:25:58.400 | There's not time in the world,

01:26:02.160 | let alone within this podcast,

01:26:03.540 | to get into all the aspects of tolerance.

01:26:05.540 | There are more than 10 different types of tolerance.

01:26:08.080 | There's functional tolerance, chronic tolerance,

01:26:09.780 | rapid tolerance, there's metabolic tolerance,

01:26:12.420 | there's psychological tolerance.

01:26:14.580 | Let's keep it simple for sake of today's discussion.

01:26:16.700 | And for those of you that are interested in learning

01:26:18.540 | about all the different types of tolerance

01:26:20.300 | and aspects of tolerance, there's an excellent review.

01:26:23.700 | We will provide a link to this.

01:26:24.980 | This was published in 2021, so it's pretty recent.

01:26:27.520 | In the journal, "Pharmacology, Biochemistry, and Behavior,"

01:26:30.700 | incidentally, or not so incidentally,

01:26:32.580 | that was the first journal I ever published in.

01:26:34.420 | So I have a particular affection for that journal.

01:26:38.400 | Nonetheless, it is called "Tolerance to Alcohol,

01:26:41.380 | a Critical Yet Understudied Factor in Alcohol Addiction."

01:26:44.640 | And while this paper does include alcohol addiction

01:26:48.500 | in the title, it's not just about alcohol addiction.

01:26:52.660 | Here's the basic summary of what tolerance is.

01:26:54.760 | First of all, tolerance refers to the reduced effects

01:26:57.860 | of alcohol with repeated exposure.

01:27:01.020 | And it is caused mainly by changes

01:27:03.260 | in neurotransmitter systems in the brain

01:27:06.120 | that are the direct consequence of the toxicity of alcohol,

01:27:09.500 | that aldehyde molecule that we talked about before.

01:27:12.660 | There's an enormous number of chemicals that change

01:27:16.360 | with repeated exposure to acetaldehyde,

01:27:20.000 | everything from GABA to dopamine to serotonin,

01:27:22.300 | second messenger systems, adenosine, and on and on.

01:27:25.120 | Rather than go into each of those in detail,

01:27:26.940 | I just want to talk about the contour of the reinforcing

01:27:31.220 | and the tolerance-inducing effects of alcohol.

01:27:33.300 | What do I mean by that?

01:27:34.620 | Well, here we are back to our old friend,

01:27:38.680 | meaning the molecule that comes up over and over again

01:27:41.660 | in these podcast episodes, which is dopamine.

01:27:44.860 | Whether or not somebody has a predisposition alcoholism

01:27:47.220 | or not, whether or not they're experienced drinker or not,

01:27:49.900 | when people initially start drinking,

01:27:51.180 | there are increases in dopamine

01:27:53.180 | or what we call dopaminergic transmission.

01:27:55.220 | Dopamine is involved in motivation, craving,

01:27:58.240 | it creates a sense of wellbeing, it increases energy.

01:28:01.220 | Again, typically only at the beginning of alcohol exposure.

01:28:05.220 | That occurs in most people as a sharp spike,

01:28:07.860 | as an increase.

01:28:08.680 | Again, if somebody does not have alcohol dehydrogenase

01:28:12.040 | or has very low levels of the enzyme

01:28:13.520 | that convert that acetaldehyde into acetate

01:28:16.420 | and metabolize alcohol, in other words,

01:28:19.060 | they will feel sick and lousy

01:28:21.260 | in a way that will override any recognition

01:28:23.420 | of the dopamine release.

01:28:24.400 | They're going to be the people that are listening to this

01:28:26.160 | and just think alcohol just makes me feel sick.

01:28:28.100 | I don't like it.

01:28:29.200 | Okay, that's a specific subcategory of people,

01:28:31.300 | but most people experience some sort of mild euphoria.

01:28:35.020 | That's why so many people drink, right?

01:28:36.660 | The current estimates are that in most countries

01:28:38.620 | and certainly in the US,

01:28:40.020 | as many as 80% of the adult legal drinking age population

01:28:44.060 | drinks alcohol.

01:28:45.060 | And that number could be even higher now

01:28:47.900 | because in the last couple of years

01:28:49.280 | there's been a trend towards increased alcohol consumption,

01:28:51.380 | especially in the wake of the pandemic

01:28:54.160 | and during the pandemic topic for another time.

01:28:57.780 | So there's an increase in dopamine

01:28:59.420 | and an increase in serotonin.

01:29:01.180 | So it's kind of an increase in wellbeing,

01:29:02.800 | an increase in mood,

01:29:04.100 | but it's a very short-lived increase.

01:29:06.860 | Very soon after and actually triggered by that increase

01:29:10.160 | is a long and slow reduction in dopamine and serotonin

01:29:15.160 | and related molecules and circuits.

01:29:17.180 | So basically what you're getting is a blip of feel good

01:29:19.660 | followed by a long, slow arc of feeling not so great,

01:29:23.540 | which is why typically people will drink again and again

01:29:26.220 | across the night.

01:29:27.140 | The key thing to understand about tolerance

01:29:31.780 | is that with tolerance,

01:29:34.300 | the duration of that long, slow reduction

01:29:37.980 | in dopamine and serotonin gets even longer.

01:29:42.140 | In other words, the negative effects of alcohol

01:29:44.640 | that happen after the initial feeling good

01:29:47.840 | extend longer and in fact get more robust.

01:29:51.260 | However, there's also a reduction

01:29:55.480 | in the reinforcing properties of alcohol.

01:29:57.300 | There's a shrinking of the feel good blip

01:30:00.200 | that happens when one first ingests alcohol.

01:30:02.660 | And this has been measured in animals and humans.

01:30:04.820 | So the first drink that somebody has,

01:30:06.860 | provided they have enough alcohol dehydrogenase

01:30:09.360 | that doesn't make them feel nauseous and sick right away,

01:30:11.820 | they feel really good.

01:30:13.800 | And then as it wears off, they feel kind of lousy

01:30:15.780 | and they want to drink more, so they might drink more.

01:30:17.700 | With each subsequent drink and even drinks

01:30:19.780 | on different nights or even different weeks,

01:30:23.480 | the amount of dopamine that's released is reduced.

01:30:26.740 | The amount of serotonin that's released is reduced.

01:30:29.140 | So what you're getting is less and less

01:30:31.540 | of the reinforcing properties of alcohol,

01:30:34.540 | the feel good stuff, and more and more

01:30:37.320 | of the punishment pain signal aspects of alcohol.

01:30:39.940 | This is the contour of chemical release in the brain

01:30:44.940 | that was referred to by my colleague,

01:30:47.980 | the incredible Dr. Anna Lemke, who's a medical doctor.

01:30:50.440 | She wrote the incredible book, "Dopamine Nation."

01:30:52.340 | She was a guest on this podcast, on Joe Rogan's podcast,

01:30:54.840 | on Rich Roll's podcast, and several other podcasts.

01:30:57.560 | World expert in addiction and she talked about

01:30:59.400 | this pleasure pain balance that extends beyond alcohol

01:31:03.080 | to things like sex and gambling and to other behaviors

01:31:07.260 | that can potentially become addictive,

01:31:08.980 | but certainly includes alcohol.

01:31:11.200 | So tolerance, it seems, is a process in which people

01:31:15.580 | are ingesting more and more alcohol as an attempt

01:31:18.940 | to get that feeling of wellbeing back,

01:31:22.480 | but what they're really getting is an extended period

01:31:24.860 | of punishment, of pain, and of malaise from the alcohol.

01:31:28.520 | Now you might say, well, how does that relate to tolerance?

01:31:30.940 | Well, it turns out what they do behaviorally,

01:31:33.340 | and when I say they, I mean, animals do this

01:31:34.940 | and humans do this, is they start drinking more and more

01:31:37.980 | in an attempt to activate those dopamine

01:31:40.580 | and serotonin neurons and receptors.

01:31:43.880 | And as they do that, there is an increase

01:31:47.380 | in alcohol dehydrogenase.

01:31:48.660 | So the enzyme that metabolizes alcohol is increased

01:31:51.460 | because the body and liver have to contend

01:31:53.420 | with all that alcohol.

01:31:54.940 | So now you've got, again, the two hit model.

01:31:57.020 | You're getting less of the feel good chemicals,

01:31:58.740 | more of the negative chemical release or pattern

01:32:02.120 | of subjective feeling, I should say,

01:32:05.060 | and you're metabolizing alcohol more quickly

01:32:09.020 | and more readily, but it's not taking you

01:32:10.860 | to a better place in terms of how you feel.

01:32:13.180 | That's one of the major underlying reasons

01:32:15.320 | for what we call tolerance.

01:32:16.580 | So if you're somebody who drinks and you notice

01:32:18.380 | that the feeling that you are seeking with alcohol

01:32:21.320 | is now requiring an additional drink or drinks, plural,

01:32:26.320 | chances are you are disrupting the dopamine

01:32:29.220 | and serotonergic systems of your brain,

01:32:31.720 | and you are doing that in a way

01:32:33.780 | that is increasing the pain and punishment signals

01:32:37.220 | that follow alcohol ingestion.

01:32:40.220 | And again, that's not just on the night

01:32:41.520 | that you're drinking, but afterwards as well.

01:32:43.700 | Is that all bad news?

01:32:44.820 | Well, pretty much, but the good news is

01:32:47.680 | that if you abstain from drinking for some period of time,

01:32:50.860 | then of course these systems reset.

01:32:52.820 | How long you need to abstain will depend

01:32:54.500 | on how much you were drinking

01:32:55.680 | and how long you were drinking for.

01:32:56.840 | Certainly people who have alcohol use disorder

01:32:58.980 | who are alcoholics, their main goal should be

01:33:01.380 | to quit alcohol completely.

01:33:02.780 | I know there's some debate about this,

01:33:04.340 | and I don't want to get into that debate

01:33:05.780 | because I'm certainly not going to try

01:33:07.420 | and direct anyone's recovery.

01:33:08.580 | There are expert counselors and MDs

01:33:12.420 | and people that can work with people.

01:33:13.820 | In fact, for some very heavy drinkers

01:33:15.900 | and people with serious alcohol use disorder

01:33:18.020 | going cold turkey, that is stopping drinking completely

01:33:20.500 | can actually be medically dangerous.

01:33:22.500 | So the path to sobriety for certain people

01:33:25.500 | looks different than the path to sobriety for other people.

01:33:27.780 | What I'm referring to here are people

01:33:29.620 | that are ingesting again somewhere between,

01:33:31.900 | on average, one to two drinks per night,

01:33:34.620 | whether or not that's done night to night

01:33:36.460 | or whether or not that's condensed to weekend use.

01:33:39.180 | I know a number of people are going to ask,

01:33:41.140 | perhaps are screaming, is drinking good for me in any way?

01:33:45.060 | For instance, many people have probably heard

01:33:47.020 | that resveratrol is good for people

01:33:49.360 | and that red wine is enriched in resveratrol.

01:33:52.100 | I hate to break it to you, but the reality is that

01:33:55.300 | if indeed resveratrol is good for us,

01:33:57.360 | and there's some debate about this,

01:33:58.620 | some people say strongly yes, some people say no,

01:34:01.200 | other people say maybe the amount of red wine

01:34:04.340 | that one would have to drink

01:34:06.100 | in order to get enough resveratrol

01:34:07.940 | in order for it to be health promoting

01:34:10.260 | is so outrageously high that it would surely

01:34:13.120 | induce other negative effects

01:34:14.440 | that would offset the positive effects of resveratrol.

01:34:17.280 | So I wish I could tell you different.

01:34:19.740 | Again, I'm not here to be the bearer of bad news,

01:34:22.440 | but the statement I just made was confirmed

01:34:24.500 | by Dr. David Sinclair when he was a guest on this podcast.

01:34:27.580 | It's confirmed by other researchers

01:34:29.620 | who work on resveratrol and related pathways.

01:34:32.280 | I wish I could tell you that red wine

01:34:34.400 | is good for your health.

01:34:35.420 | And indeed it might be through some other mechanisms.

01:34:39.300 | So for instance, there have been studies

01:34:40.940 | of low to moderate red wine consumption.

01:34:44.240 | This would be anywhere from one to four glasses per week.

01:34:48.420 | And I don't mean enormous glasses,

01:34:50.180 | I mean six ounce glasses of red wine.

01:34:53.140 | And in those cases, some of the stress reduction

01:34:56.740 | that can be induced by consumption of red wine

01:34:59.260 | may be some of the other micronutrients and components

01:35:02.480 | within red wines, in particular red wines

01:35:04.500 | that come from particular grapes,

01:35:05.900 | and this gets really nuanced and frankly is not well worked

01:35:09.420 | out in the peer reviewed literature,

01:35:11.580 | certainly not clinical trials,

01:35:13.660 | at least not that I'm aware of.

01:35:14.780 | Tell me if you're aware of a great clinical trial on this.

01:35:17.460 | Well, there may be some positive effects

01:35:19.160 | of that very low level of consumption.

01:35:22.260 | I'm not trying to take away anybody's red wine.

01:35:24.340 | I'm not trying to take away anybody's anything.

01:35:27.540 | I would be remiss, however, if I didn't tell you

01:35:31.980 | that resveratrol as the argument for drinking

01:35:36.240 | and drinking red wine in particular is just not a good one.

01:35:39.060 | It's just not supported by the peer reviewed research.

01:35:42.180 | A few other things about alcohol and health.

01:35:45.620 | The beginning of the episode,

01:35:46.860 | I referenced a study showing that indeed

01:35:49.860 | not just heavy alcohol consumption

01:35:51.960 | of 12 to 24 more drinks per week,

01:35:53.660 | but also light to moderate alcohol consumption

01:35:56.540 | of any type, wine, beer, spirits, et cetera,

01:35:59.740 | does reduce the thickness of the brain.

01:36:03.240 | It really does reduce cortical thickness.

01:36:05.260 | In fact, it actually scales with the amount of alcohol

01:36:09.420 | that people drink.

01:36:10.500 | And this has been well-documented

01:36:12.780 | in a number of different studies.

01:36:13.820 | I can provide a link to several of these.

01:36:16.120 | One of the more striking ones actually shows

01:36:17.780 | that there's almost a dose dependent increase

01:36:21.320 | in shrinkage of the gray matter volume

01:36:23.300 | and in these white matter tracks,

01:36:24.700 | these axons, these wires as it would,

01:36:27.940 | that connect different neurons

01:36:29.820 | as a function of how much alcohol people drink.

01:36:31.540 | And that's also what's been seen in this recent study

01:36:34.100 | that I referenced at the beginning

01:36:35.180 | and that's in the show note captions.

01:36:36.960 | So again, probably the best amount of alcohol to drink

01:36:40.040 | would be zero glasses per week or ounces per week.

01:36:43.620 | For those of you drinking low amounts of alcohol,

01:36:45.680 | make sure you're doing other things to promote your health.

01:36:48.940 | And for those of you that are drinking moderate,

01:36:51.780 | and certainly for those of you that are heavy drinkers,

01:36:53.720 | please do everything you can to move away from that

01:36:56.520 | and to quit entirely.

01:36:58.020 | But even for the moderate consumers of alcohol,

01:37:01.520 | you are going to want to be aware

01:37:03.940 | of some of the negative health effects

01:37:05.140 | and do things to offset those

01:37:06.640 | if indeed you're not going to stop drinking

01:37:09.180 | or reduce your intake.

01:37:10.480 | One of the really bad effects of alcohol,

01:37:12.960 | but that's extremely well-documented,

01:37:15.580 | is the fact that alcohol,

01:37:18.220 | because of this toxicity of acetaldehyde

01:37:20.960 | and related pathways, can alter DNA methylation.

01:37:24.420 | It can alter gene expression.

01:37:26.180 | That can be many things in different tissues,

01:37:28.620 | but it is associated with a significant increase

01:37:33.620 | in cancer risk, in particular breast cancer.

01:37:36.420 | And in particular, because breast tissue

01:37:38.980 | is present in both males and females,

01:37:40.500 | but in women, it's especially vulnerable

01:37:43.360 | to some of the DNA methylation changes.

01:37:45.820 | Well, breast cancer in women

01:37:48.060 | has a relationship to alcohol intake

01:37:49.820 | and alcohol intake has a relationship

01:37:51.300 | to breast cancer in women.

01:37:53.060 | In fact, there has been proposed to be

01:37:56.540 | anywhere from four to 13% increase

01:38:01.100 | in risk of breast cancer

01:38:03.080 | for every 10 grams of alcohol consumed.

01:38:05.900 | How much is 10 grams?

01:38:07.140 | Well, there we need to think a little bit

01:38:08.740 | about the variation in the amount of alcohol

01:38:10.600 | in different drinks across the world.

01:38:12.260 | Different countries serve different sized drinks

01:38:14.140 | and have different concentrations of alcohol

01:38:15.700 | in those drinks.

01:38:16.700 | So without going down too much of a rabbit hole

01:38:18.960 | and just giving you some good rules of thumb to work with,

01:38:21.800 | there have been studies of the percentage of alcohol

01:38:25.020 | included in different drinks

01:38:26.080 | and the sizes of different drinks

01:38:27.440 | that are served in different countries.

01:38:28.620 | And here's a kind of a patchwork of those findings.

01:38:32.740 | In Japan, one beer, one glass of wine,

01:38:37.220 | or one shot of liquor as it's served there

01:38:40.080 | tends to include anywhere from seven to eight grams

01:38:42.740 | of alcohol.

01:38:44.180 | In the US, one beer, which generally is 12 ounces.

01:38:48.260 | If it's in a bottle,

01:38:49.320 | one glass of wine or a shot of liquor

01:38:52.680 | tends to include about 10 to 12 grams of alcohol.

01:38:57.680 | And in Russia,

01:39:00.200 | one drink of the various sorts that I just described

01:39:03.660 | typically will have as much as 24 grams of alcohol

01:39:09.040 | because of the differences in the concentration of alcohols

01:39:12.780 | and the sizes of drinks

01:39:14.600 | that are poured in these different countries, okay?

01:39:16.820 | Of course, there are other countries in the world

01:39:18.200 | those countries are also vitally important,

01:39:19.900 | but those are the ones that extracted from the studies

01:39:22.700 | that I could find.

01:39:23.660 | What does this mean?

01:39:26.020 | Well, what we're talking about is that

01:39:27.560 | for every 10 grams of alcohol consumed,

01:39:29.940 | so that's one beer in the US,

01:39:32.500 | maybe a little bit more than one beer in Japan,

01:39:34.900 | or basically a third of a drink in Russia,

01:39:38.900 | there's a four to 13% increase in risk of cancer.

01:39:43.900 | That's pretty outrageous, right?

01:39:46.600 | And you might think, wait, how could it be that

01:39:49.340 | this stuff is even legal?

01:39:50.620 | Well, look, as I described before, it's a toxin.

01:39:54.020 | It's also a toxin that people enjoy the effects of.

01:39:57.140 | I mean, in the US, at least they tried prohibition

01:40:00.420 | that certainly did lead,

01:40:02.300 | yes, did lead to a reduction in alcohol-induced

01:40:06.820 | health disorders, in particular cirrhosis of the liver.

01:40:09.500 | It also led to a lot of crime

01:40:11.180 | because it became a substance

01:40:12.980 | that a lot of people still wanted

01:40:15.020 | and that people were willing to break the law

01:40:17.220 | in order to provide, or I should say to sell and provide.

01:40:20.780 | But the point is that the more alcohol people drink,

01:40:24.200 | the greater their increase of cancer,

01:40:26.500 | in particular breast cancer.

01:40:27.620 | And that's because of the fact that alcohol

01:40:31.060 | has these effects on cells

01:40:33.460 | that include changes in gene expression.

01:40:36.540 | And cancer, that is the growth of tumors,

01:40:39.380 | is a dysregulation in cell cycles, right?

01:40:42.160 | A tumor is a aggregation or the proliferation,

01:40:45.520 | aggregation is stuff sticking together, by the way.

01:40:47.560 | Proliferation is stuff duplicating.

01:40:50.160 | A proliferation and aggregation of cells

01:40:52.960 | that could be a glioma, glial cells, glioma, brain tumor,

01:40:56.720 | it could be lymphoma, so within the lymph tissue, et cetera.

01:41:00.640 | The mutations that alcohol induces to cause this

01:41:03.960 | are wide ranging.

01:41:05.260 | Some of those are starting to start to be understood.

01:41:07.240 | For those of you that are interested in cell biology,

01:41:08.960 | I'll just mention that the PD-1 pathway,

01:41:11.480 | again, this is super specialized

01:41:14.160 | and for the aficionados only, you don't need to know this.

01:41:17.180 | The PD-1 pathway seems to be upregulated.

01:41:19.280 | And we knew this from the discussion earlier,

01:41:21.840 | there's a downregulation

01:41:23.460 | in some of the anti-inflammatory molecules

01:41:27.760 | that help suppress this proliferation of cancers.

01:41:31.360 | Nowadays, there's a lot of interest in the fact

01:41:33.320 | that the immune system is constantly combating cancers

01:41:37.360 | that exist in us all the time.

01:41:38.920 | Little tumors start growing and our immune system

01:41:41.200 | goes and gobbles them up.

01:41:42.660 | Little tumors start growing,

01:41:44.020 | the immune system senses inflammation,

01:41:45.880 | sends out these incredible cells,

01:41:47.300 | these killers B cells and T cells and beats them up.

01:41:50.260 | Cancers proliferate and take hold and cause serious problems

01:41:55.160 | when the proliferation of cells

01:41:57.260 | exceeds the immune system's ability to gobble up

01:42:00.000 | and remove those cells.

01:42:00.920 | There are other mechanisms of regulating cancers,

01:42:02.920 | but that's one of the primary one.

01:42:04.240 | And alcohol hits it, again, it's a two hit model.

01:42:07.240 | It increases tumor growth and it decreases

01:42:11.340 | the sorts of molecules that suppress and combat tumor growth.

01:42:15.280 | So again, even low to moderate amounts of alcohol

01:42:18.720 | can be problematic for sake of cancers,

01:42:20.660 | in particular breast cancers.

01:42:22.320 | Epidemiologists and health specialists love to try

01:42:26.640 | and compare different substances

01:42:28.680 | in terms of how bad they are.

01:42:30.260 | Rarely do they compare substances

01:42:32.280 | in terms of how good they are, but sometimes they do.

01:42:35.700 | And what they'll sometimes tell you

01:42:38.020 | and what you can find in the literature

01:42:39.340 | is that ingesting 10 to 15 grams of alcohol a day,

01:42:42.620 | so that would be like one beer in the US,

01:42:44.380 | one glass of wine,

01:42:45.460 | is the same as smoking 10 cigarettes a day.

01:42:48.500 | Frankly, it's hard to make that direct relationship

01:42:53.020 | really stick because it's a question of

01:42:56.020 | how long people inhale,

01:42:57.240 | do they have a predisposition to a lung cancer, et cetera.

01:43:00.580 | But even if that number is off

01:43:03.420 | by plus or minus two cigarettes,

01:43:06.660 | or even if that number with the equivalent

01:43:09.540 | of one glass of wine equals one cigarette per day,

01:43:12.260 | I think there's general consensus now

01:43:14.440 | that nicotine consumed by vaping or by cigarette,

01:43:18.500 | it's bad for us in terms of lung cancer

01:43:22.540 | and other forms of cancer.

01:43:24.020 | And for some reason, I don't know why,

01:43:26.500 | because this knowledge about alcohol and cancer

01:43:29.400 | and these established relationships

01:43:31.660 | have been known since the late 1980s.

01:43:33.880 | The first kind of landmark paper on this

01:43:36.220 | was published in 1987.

01:43:37.620 | I can provide a link to that paper.

01:43:38.800 | It's actually quite interesting to read.

01:43:41.820 | Well, the relationship is there

01:43:45.240 | and yet we don't often hear about it, right?

01:43:47.460 | In fact, before researching this episode,

01:43:49.560 | I had heard before that alcohol can increase cancer risk,

01:43:52.960 | but I wasn't aware of just how strong

01:43:55.020 | that relationship is.

01:43:56.280 | Because of the serious nature of what we're talking about

01:43:58.800 | and because I would hate to be confusing

01:44:01.780 | or misleading to anybody,

01:44:03.180 | I wanted to just emphasize that this statistic

01:44:05.760 | that there is a 4 to 13%,

01:44:07.860 | depending on which study you look at,

01:44:09.280 | a 4 to 13% increase in the risk of cancer,

01:44:12.460 | in particular breast cancer,

01:44:13.680 | for every 10 grams of alcohol consumed,

01:44:17.200 | that's 10 grams per day.

01:44:18.740 | So that's one drink per day.

01:44:20.800 | But I do want to emphasize

01:44:22.960 | that if that equates to seven drinks per week

01:44:27.160 | and all those seven drinks are being consumed

01:44:29.800 | on Friday and Saturday,

01:44:31.160 | it still averages to 10 grams per day.

01:44:33.800 | And I also want to emphasize

01:44:35.140 | that there are things that people can do

01:44:37.080 | to at least partially offset

01:44:38.720 | some of the negative effects of alcohol

01:44:40.880 | as it relates to predisposition

01:44:43.320 | to the formation of certain kinds of tumors and cancers.

01:44:46.120 | I also want to be clear before I say it

01:44:49.480 | that doing the things I'm about to tell you

01:44:51.980 | is not a guarantee that you're not going to get cancer,

01:44:55.760 | nor is it a guarantee that alcohol

01:44:58.640 | is not going to lead to an increased predisposition

01:45:02.420 | for certain kinds of cancers.

01:45:03.880 | And the two things are consumption of folate

01:45:07.220 | and other B vitamins, especially B12.

01:45:10.400 | You know, the consumption of folate and B12

01:45:13.320 | has been shown to decrease cancer risk

01:45:16.980 | in people that ingest alcohol,

01:45:19.180 | but not completely offset it.

01:45:21.500 | Why that is isn't exactly clear.

01:45:23.420 | It probably has something to do with the relationship

01:45:25.960 | between folate and B12 and other B vitamins

01:45:29.800 | in gene regulation pathways that can lead to tumor growth.

01:45:33.140 | At some point soon, we will get an expert in cancer biology

01:45:37.100 | and in particular in breast cancer biology on the program,

01:45:40.800 | and we can ask them about this,

01:45:42.400 | but I realize this is going to raise a number of questions

01:45:45.180 | and maybe even cause some of you to go out there

01:45:47.360 | and start taking folate and other B vitamins and B12.

01:45:51.680 | Not incidentally, a lot of the reported

01:45:55.680 | hangover supplements and treatments include folate and B12.

01:46:00.340 | I don't know if they had the cancer literature in mind

01:46:02.840 | when they created those supplements and products.

01:46:06.040 | I doubt they did.

01:46:07.880 | Alcohol really does disrupt B vitamin pathways,

01:46:11.220 | both synthesis pathways and utilization pathways.

01:46:14.240 | So sometimes you'll hear, oh, you know,

01:46:15.780 | if you get your B vitamins,

01:46:16.780 | it helps you recover from hangover more quickly.

01:46:20.280 | Again, the literature doesn't support that,

01:46:22.460 | but also again, there aren't a lot of studies,

01:46:24.560 | but more to the point as it relates to alcohol

01:46:28.080 | and the formation of tumors and cancers,

01:46:30.040 | it does appear that decreased folate

01:46:33.120 | and other B vitamins like B12 are partially responsible

01:46:36.760 | for the effect of alcohol and increasing cancer risk.

01:46:40.940 | And it does appear that consuming adequate amounts

01:46:45.240 | of folate and B12 might, again,

01:46:47.360 | might partially, really want to bold face and underline

01:46:50.620 | and highlight, partially offset some of that increased risk.

01:46:54.320 | There's an additional category

01:46:55.720 | that I want to highlight, of course,

01:46:58.160 | and this is vitally important to state,

01:47:01.200 | even though it's obvious,

01:47:02.580 | which is that people who are pregnant

01:47:05.400 | should absolutely not consume alcohol.

01:47:09.080 | Fetal alcohol syndrome is well-known and established.

01:47:13.240 | It's terrible.

01:47:14.320 | Fetuses experience diminished brain development

01:47:18.160 | that's often permanent, diminished limb development,

01:47:21.100 | diminished organ development in the periphery,

01:47:23.040 | meaning the heart, the lungs, the liver, et cetera.

01:47:25.640 | Ingesting alcohol while pregnant is simply a bad idea.

01:47:28.840 | And the reason I say this at all is,

01:47:31.840 | first of all, it's important to include

01:47:33.280 | in an episode like this,

01:47:34.240 | but also because we can look at two things.

01:47:37.920 | First of all, we can look at mechanism

01:47:39.400 | and then we can also look at some of the lore

01:47:42.000 | that still sadly exists out there.

01:47:44.920 | Let's take care of the lore that sadly exists first.

01:47:48.400 | If you look online,

01:47:50.760 | you will sometimes be able to find, sadly,

01:47:54.440 | that some people believe that certain kinds of alcohol

01:47:58.520 | are not detrimental to fetuses.

01:48:00.360 | They'll say, well, champagne is safe

01:48:02.480 | for a pregnant mother to drink, but beer is not.

01:48:05.320 | That is absolutely categorically false.

01:48:08.400 | Alcohol is alcohol.

01:48:10.300 | There is no evidence whatsoever

01:48:12.000 | that consuming certain types of alcohol

01:48:13.720 | is safer for fetuses than others.

01:48:15.560 | Alcohol is a toxin,

01:48:16.640 | and the reason fetal alcohol syndrome exists

01:48:19.140 | is because the ability of that toxin

01:48:21.980 | to disrupt cellular processes.

01:48:24.160 | Remember tumor growth and the way that alcohol

01:48:27.300 | can accelerate tumor growth by proliferation of cells,

01:48:30.740 | the wrong cells, the ones you don't want to proliferate?

01:48:33.560 | Well, all of embryonic development,

01:48:35.380 | all of fetal development, it's not the growth of a tumor,

01:48:38.340 | it's obviously the growth of an embryo,

01:48:39.940 | and it's done in a very orchestrated way.

01:48:43.440 | I started off studying brain development.

01:48:45.100 | That's where I got my beginnings in neurobiology,

01:48:47.720 | and I still teach embryology to medical students

01:48:50.680 | and graduate students.

01:48:52.440 | The set of coordinated processes

01:48:55.080 | that has to take place from conception to birth

01:48:58.280 | in order to give rise to a healthy embryo

01:49:00.440 | is so dynamically controlled and so exquisitely precise

01:49:05.440 | with checkpoints and recovery mechanisms

01:49:07.940 | and redundancy in the genes that are expressed

01:49:10.360 | to make sure that if anything goes wrong,

01:49:11.920 | it's repaired, et cetera.

01:49:13.720 | Alcohol as a mutagen, I haven't used that word yet,

01:49:17.640 | but a substance that can mutate DNA

01:49:21.040 | through alterations in DNA methylation

01:49:23.120 | and these checkpoints in the cell cycle.

01:49:25.280 | Alcohol as a mutagen is one of the worst things

01:49:29.300 | that a developing embryo can be exposed to.

01:49:31.680 | And again, because it's water-soluble and fat-soluble,

01:49:34.880 | ingestion of alcohol when people are pregnant

01:49:36.680 | passes right to the fetus.

01:49:39.040 | Now, I realize that a number of people out there

01:49:41.540 | might be thinking, "Oh goodness, you know,

01:49:42.920 | I didn't realize I was pregnant

01:49:45.120 | until a certain stage of pregnancy,

01:49:46.900 | and before I realized I was ingesting alcohol."

01:49:50.080 | Obviously, one can't undo what's been done,

01:49:53.900 | but I want to also emphasize that fetal alcohol syndrome,

01:49:57.180 | while yes, there's a full-blown syndrome

01:49:59.520 | that manifests as changes in the craniofacial development

01:50:02.080 | that are very obvious, and you can look these up,

01:50:03.920 | you've probably seen these before,

01:50:05.080 | the pictures before, rather.

01:50:06.720 | It has to do with eye spacing, forehead size,

01:50:08.680 | a number of other features of the craniofacial development,

01:50:11.700 | and of course, stuff's going on in the brain too.

01:50:13.600 | It's along a continuum, so it is possible

01:50:16.600 | that some of the changes that occur are more minor,

01:50:20.040 | and thankfully, the young brain,

01:50:22.680 | in particular the early postnatal brain,

01:50:24.520 | is incredibly plastic.

01:50:25.600 | There are things that can be done

01:50:26.780 | in order to help recover neural circuits

01:50:28.780 | that didn't develop well, et cetera.

01:50:31.780 | But even though it's somewhat obvious

01:50:34.920 | or should be obvious, I really want to make clear

01:50:37.600 | that there's zero evidence whatsoever

01:50:39.020 | that certain forms of alcohol are safer

01:50:40.860 | for pregnant women to ingest than others.

01:50:42.400 | It's absolutely wrong.

01:50:43.600 | No one who's pregnant should be ingesting alcohol whatsoever,

01:50:47.960 | and certainly, if people feel like they can't avoid alcohol

01:50:51.720 | while pregnant, they really need to work with somebody

01:50:54.080 | to make sure that it just absolutely doesn't happen

01:50:55.920 | because it is so detrimental to the developing fetus.

01:50:58.840 | Lastly, I want to talk about the effects

01:51:00.380 | of alcohol on hormones, and I want to distinguish

01:51:03.880 | between low amounts of alcohol intake,

01:51:06.400 | higher amounts of alcohol intake,

01:51:08.000 | and again, this chronic alcohol intake

01:51:09.920 | versus occasional use versus really chronic use,

01:51:13.560 | meaning alcoholic or alcoholic use disorder

01:51:16.560 | where people are drinking an immense amount

01:51:18.320 | on an ongoing basis.

01:51:20.380 | The literature on alcohol and hormones is quite extensive,

01:51:23.140 | and there are, of course,

01:51:23.980 | many, many different types of hormones.

01:51:25.360 | The hormones that most often get mentioned

01:51:28.000 | and talked about on this podcast are the hormones testosterone

01:51:30.440 | and estrogen, which are present in both men and women,

01:51:33.080 | in both men and women are important for things like libido.

01:51:37.140 | They're also responsible for sexual development,

01:51:40.320 | actual development of the genitalia

01:51:42.520 | before birth and after birth.

01:51:43.920 | They're responsible, for instance,

01:51:45.200 | estrogen is important for memory and cognition.

01:51:47.360 | You never want to drop estrogen too low in men or women

01:51:49.840 | 'cause it can disrupt cognition and joint health, et cetera.

01:51:52.840 | To keep this discussion relatively constrained,

01:51:56.820 | it's fair to say that alcohol, and in particular,

01:52:00.080 | the toxic metabolites of alcohol,

01:52:03.320 | increase the conversion of testosterone to estrogen.

01:52:07.640 | Now, this occurs in a number of different tissues.

01:52:10.620 | This is not just occurring in the testes of males.

01:52:12.720 | This is occurring in lots of different tissues,

01:52:14.320 | and I'll refer you to a excellent review.

01:52:16.380 | We'll provide a link in the show note captions.

01:52:18.280 | This is a paper that was published in the year 2000,

01:52:21.280 | but the data are still quite strong.

01:52:23.640 | The journal is called, of all things, Alcohol.

01:52:27.920 | There's, yes, literally a journal called Alcohol

01:52:31.120 | for the publication of data and reviews

01:52:33.560 | on alcohol and its effects.

01:52:34.900 | And the title of the paper is,

01:52:36.000 | Can Alcohol Promote Aromatization of Androgens to Estrogens?

01:52:39.240 | Aromatization is this process of the conversion

01:52:41.640 | of testosterone and other androgens to estrogens

01:52:44.600 | through things like aromatase enzyme.

01:52:46.720 | And this is a beautiful review that describes every tissue

01:52:50.760 | or near every tissue from the ovary in females

01:52:54.800 | to the placenta, to the liver, to the testes,

01:52:58.420 | in which alcohol can increase the aromatization

01:53:02.900 | of testosterone to estrogen.

01:53:04.040 | Now, in females, this may be part of the reason

01:53:06.640 | why there's an increase in estrogen-related cancers.

01:53:09.720 | Breast cancer can be either estrogen-related

01:53:12.040 | or non-estrogen-related.

01:53:13.120 | There are other types of estrogen-related cancers

01:53:14.920 | outside of breast cancer,

01:53:16.720 | but it appears that one reason why alcohol increases

01:53:19.600 | the risk of breast cancer is because of this aromatization

01:53:22.920 | from, of testosterone, excuse me, to estrogen.

01:53:26.560 | In males, accelerated or abnormal conversion

01:53:31.560 | of testosterone to estrogen can actually lead to growth

01:53:34.100 | of the breast tissue in males, so-called gynecomastia,

01:53:37.280 | or other effects of high estrogen,

01:53:39.800 | or I should say of altered testosterone-estrogen ratios,

01:53:43.280 | 'cause that's really what's important.

01:53:45.400 | And these can include things like diminished sex drive,

01:53:48.840 | increased fat storage, and a number of other things

01:53:51.560 | that I think most people would find to be negative effects.

01:53:55.300 | I once talked about the fact that drinking alcohol

01:53:58.640 | can increase the aromatization of testosterone to estrogen.

01:54:01.220 | I posted that online, and I didn't get attacked,

01:54:03.560 | but I did get criticized for the fact

01:54:07.560 | that it has been shown, yes, has been shown,

01:54:09.940 | that small amounts of alcohol ingestion,

01:54:11.800 | so five grams or so of alcohol ingestion,

01:54:14.120 | this would be half a glass of wine or half a glass of beer,

01:54:16.400 | at least in some studies showed increases in testosterone,

01:54:19.740 | which was kind of surprising,

01:54:21.160 | but I should point out other studies have shown

01:54:23.840 | that alcohol ingestion causes decreases

01:54:26.720 | in testosterone over time.

01:54:29.160 | So there's always this issue

01:54:30.640 | of whether or not you're looking at a study

01:54:31.640 | of acute exposure versus chronic exposure,

01:54:33.840 | one dose versus multiple doses and exposure.

01:54:37.040 | I think it's fair to say,

01:54:39.540 | based on my read of the literature,

01:54:41.000 | this review and other reviews

01:54:42.700 | that focus more particularly on humans,

01:54:45.040 | that regular ingestion of alcohol

01:54:47.200 | is going to increase estrogen levels,

01:54:49.540 | whether or not you're male or female,

01:54:50.880 | and it's largely doing that through the aromatization process

01:54:54.200 | by increasing the aromatase enzyme.

01:54:57.360 | Yes, there's some dose dependence,

01:54:59.040 | but I think if you're somebody who's trying

01:55:00.440 | to optimize your testosterone to estrogen ratio,

01:55:03.240 | regardless of whether or not you're male or female,

01:55:05.300 | well, then most certainly you're going to want

01:55:06.880 | to avoid drinking too much alcohol.

01:55:09.440 | So we've covered a lot of topics and data

01:55:11.840 | related to the mechanisms of alcohol,

01:55:14.760 | hangover, tolerance, cancer risk, et cetera.

01:55:18.160 | I acknowledge that I've mainly talked to you

01:55:19.960 | about the negative effects of alcohol.

01:55:21.940 | I want to acknowledge that many people enjoy alcohol

01:55:26.560 | in moderation or even light drinking,

01:55:30.120 | the occasional drink or the occasional two drinks,

01:55:32.720 | or maybe even on average, one drink per night,

01:55:35.380 | so seven drinks per week.

01:55:37.100 | I'm certainly not here to tell you what to do

01:55:39.140 | and what not to do.

01:55:40.760 | I do find it immensely interesting, however,

01:55:43.660 | that first of all, alcohol is a known toxin

01:55:46.760 | to the cells of the body.

01:55:47.920 | Some of you might immediately say,

01:55:49.080 | well, wait, what about hormesis?

01:55:50.520 | What about this phenomenon where

01:55:51.960 | if we regularly ingest a toxin, it makes us stronger?

01:55:54.760 | In other words, what doesn't kill us makes us stronger.

01:55:57.120 | There's some reason to believe that might be beneficial

01:56:00.760 | in terms of some forms of cellular resilience,

01:56:04.040 | maybe, maybe, no, sorry, it doesn't work that way.

01:56:07.640 | There are processes of hormesis in which, for instance,

01:56:10.880 | exposing yourself safely to increases in adrenaline

01:56:14.680 | through ice baths or other things that increase adrenaline

01:56:17.800 | can raise your so-called stress threshold.

01:56:20.080 | But here we're talking about cellular stress

01:56:22.720 | and damage to cells.

01:56:24.760 | So my read of the literature, and again, this is my read,

01:56:27.920 | and I invite others to provide studies

01:56:30.800 | or I would prefer actually collections of studies

01:56:33.240 | that point in the direction, if they exist,

01:56:35.880 | that alcohol can be beneficial.

01:56:39.080 | But my read of the literature, or I should say,

01:56:42.340 | my understanding of what I would call the center of mass

01:56:45.040 | of the literature on alcohol is that no consumption,

01:56:49.640 | zero consumption, consumption of zero ounces of alcohol

01:56:53.840 | is going to be better for your health

01:56:55.980 | than low to moderate consumption of alcohol.

01:56:59.120 | And that low to moderate consumption of alcohol

01:57:02.340 | is going to be better for you, of course,

01:57:04.360 | than moderately high to high alcohol consumption

01:57:08.480 | on the order of 12 to 24 or more drinks per week.

01:57:13.160 | I realize that for most people listening to this,

01:57:15.660 | it's probably low to moderate alcohol consumption

01:57:19.680 | that is part of their standard repertoire.

01:57:23.040 | And I'm not here to give you justification for doing that,

01:57:26.360 | nor am I going to tell you not to do that.

01:57:28.360 | I would like you to consider perhaps, however,

01:57:31.540 | the negative effects that we understand

01:57:33.920 | and that are documented.

01:57:34.800 | For instance, the negative effects of alcohol

01:57:37.560 | in the gut microbiome and the things that you can do

01:57:40.480 | to better support your gut microbiome.

01:57:42.560 | The negative effects on the stress system,

01:57:45.000 | that HPA axis that we talked about earlier,

01:57:47.140 | and the fact that even low to moderate levels

01:57:49.580 | of alcohol consumption can increase our levels of stress

01:57:52.080 | when we're not drinking.

01:57:53.880 | And to think about acquiring some tools

01:57:57.320 | and getting some proficiency with tools,

01:58:00.080 | behavioral or otherwise,

01:58:01.140 | that can help you with stress modulation

01:58:03.280 | that don't involve alcohol consumption.

01:58:06.120 | Again, the point here is to illustrate

01:58:09.000 | where the problems lie with alcohol consumption,

01:58:11.080 | but also what I've tried to do is to point you

01:58:13.800 | to some resources that can help offset

01:58:15.780 | some of those negative effects.

01:58:17.320 | Will they offset all the effects?

01:58:19.400 | I can't say that for sure,

01:58:20.940 | but certainly taking measures

01:58:24.000 | to offset some of the negative effects

01:58:25.560 | of any alcohol consumption

01:58:26.760 | that you might be having or doing

01:58:29.640 | is going to be beneficial to you.

01:58:31.520 | And those tools and protocols

01:58:32.740 | are going to be health promoting in any case.

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

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