This Podcast Will Kill You - Ep 85 Alcohol: Beer for Thought

Episode Date: November 2, 2021

To say that alcohol is a part of human culture is a bit of an understatement. The relationship our species has with alcohol can be traced so far back that we see evidence of it in our DNA, in the way that humans, somewhat unique among mammals, gained the ability to more efficiently metabolize dietary ethanol. But while many of us have personal experience with the effects (and unpleasant aftereffects) that alcohol has on our body, how much do we know about why it makes us feel the way it does? What is alcohol doing to our bodies, to our brains? In this episode, we take a long look at this compound, from the varied effects it has on our bodies to the long history it shares with humans. Tune in to our Season 4 finale to hear why hangovers exist, how fermenting fruits on the forest floor led us to intentional production, and the truth behind all of those headlines advocating for a glass of red wine a day to keep the doctor away. See omnystudio.com/listener for privacy information.

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Raising my cup, I invite the bright moon and turn to my shadow. We are now three. But the moon doesn't understand drinking, and my shadow follows my body like a slave. For a time, moon and shadow will be my companions, a passing joy that should last through the spring. I sing and the moon just wavers in the sky. I dance and my shadow whips around like mad.

While lucid still, we have such fun together, but stumbling drunk each staggers off alone. Bound forever, relentlessly roam, reunited at last on the distant river of stars. Wow. I really like that little poem. I do too. So that poem was by Li Bai, also known as Lee Po, who was, according to this source,

one of the greatest poets of China's Tang Dynasty, or of all of history, perhaps. Leibai was a martial artist, an academic genius, and also a lover of wine, and a member of the group Six Idlers of the Bamboo Brook, which was a group dedicated to literature and drinking. And in general, people at the time would only indulge socially. So this poem, one of his most famous, is exploring the problems of drinking alone. Yeah, all the way back from the 8th century. The 8th century.

And the poem that I read was translated by David Bowles from the original Chinese. And we'll post the link on our website. Yeah. Well, hi, I'm Aaron Welsh. And I'm Aaron Omen Updike. And this is This Podcast Will Kill You. It is. And it's a big episode for a couple of reasons.

Reason number one is that it's our season finale. It's our season four finale. Yeah, four seasons, four finalees. This is a big one. Can you picture us four years ago when we were doing our first season in my back bedroom in our tiny house? Like, can you, could you ever have imagined that we would be here doing this now, Aaron? You know what? I don't know if I, like, dared to hope that we would still be doing it.

But I think it's kind of funny because I think that neither of us maybe would have been that surprised. Because we had lists of like episodes we wanted to cover up to like five seasons worth all the way back then. I think the thing that would have really shocked us and we would not have believed is just like is our listenership being so incredible and so supportive and so wonderful. Yeah. It's you all listeners, thank you so much. we would not be still making this podcast without you, or if we were, it definitely wouldn't be as much fun. Yeah, it's true. Yeah, so after this episode, don't worry, we will be coming back.

So it's kind of like not that sad in a way. Because, you know, we are, I think it would be a lie to say that we're not looking forward to the break a bit. No, we're highly looking forward to it. Yeah, just a little bit of time to rest our brains. and to get some other stuff done in the background. And, you know, if you're looking for more of TPWKY to, like, fill that need while you're gone, you should definitely check out our reading lists, our bookshop.org affiliate account, our Goodreads list, which, by the way, I'm not allowed to add any more books.

I've capped it at 100. Like, I've added 100 books so far, and so I can't add any more. So if there's a helpful listener out there that wants to add the books that I mentioned, would be lovely. That's hilarious. Oh my goodness. Problems of a podcaster. Okay, so that's one of the reasons that this is a big episode. The other reason is because today we're talking about alcohol. Alcohol. Like all of it, just alcohol. Yeah. You know, it sounded fun. It still sounds fun. It sounded manageable. Yeah, yeah.

Well, we'll see if it was. Yeah, you be the judge. Yeah, you guys tell us. Well, it wouldn't be an episode of TPWKY or just an episode of a podcast about alcohol without a quarantini. Exactly. So, what are we drinking this week? We're drinking poor choices. Get it like P-O-U-R.

I think this is the second poor-related pun that we've done. This season. Yep. This season. But it's a really good one. It is. It is a really good one. And in addition to having a really good name, it's also a really fantastic drink.

And I'm not exaggerating. Tell us what's in it, Aaron. So you start with Mead. And we chose Mead because Mead is one of the oldest alcoholic beverages, also known as Honey. wine. And then we kind of did a little fun side step. We're doing a shrub. A shrub. If anyone hasn't had a shrub before, it's basically like, you know, drinking vinegar. Like it's, you make a little recipe with macerated fruit usually or like pulped fruit and then some sort of sweetener and then vinegar and some spices if you want. And you let it sit and then you, you know, filter it out. And

It's absolutely delicious. I made a shrub for this of honey crisp apples and honey, apple cider vinegar, the zest of a lemon, all-spice, anise, and cinnamon sticks. Yum. Also, don't be afraid of the sound of a vinegar drink. It's actually delicious. It's like really complex and delicious and you can do so much with them. Yeah, it makes a very good placebo rita. And don't worry, we'll post the full recipe.

for that quarantini and the non-alcoholic placebo Rita on our website, this podcast with kill you.com, and all of our social media channels. We will. Other business. Other business. Our website. There's lots of good stuff on there.

You can find all of our sources for all of our episodes. You can find links to, like I said, our bookshop.org affiliate account and Goodreads list. You can find links to Patreon, to our merch, to transcripts, and also I am excited to announce that Bloodmobile, who provides the music for this episode and all of our episodes, is now on Spotify, and we will post a link to that as well. So definitely check all of that stuff out. Is that all of our business today, Erin?

I think so. Should we dive in? Can we dive in? I think that we can. We'll take a sip and a break and then get to it. Perfect, perfect. Dinner shows up every night, whether you're prepared for it or not. And with Blue Apron, you won't need to panic order takeout again. Blue Apron meals are designed by chefs and arrive with pre-portioned ingredients so there's no meal planning and no extra grocery trip.

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amazing, and they come in a bunch of different washes, so I'm about to go order some more. Refresh your wardrobe with Quince. Go to quince.com slash this podcast to get free shipping on your order and 365-day returns, now available in Canada, too. That's Q-U-I-N-C-E.com slash this podcast to get free shipping and 365-day returns. Quince.com slash this podcast. So alcohol. By which I mean, Aaron, ethanol. assuming that's what you mean. Okay, good. Yeah, by the way, I think we're going to be using these interchangeably throughout. Okay. We for sure. Yeah, ethanol is the form of alcohol that we drink. It's the form that's used for recreational purposes. So when we say alcohol, that's what we're talking

about in this context. All right. So ethanol, alcohol, is a psychoactive drug. I think it's important to frame it that way because, A, that is, in fact, what it is. And, be, it's not uncommon that we frame it either as something completely harmless or fairly harmless or on the flip side as a recreational substance or something that is really bad, right? What is the definition of a psychoactive drug? So glad you asked, Erin. I actually don't know if I have a formal definition. But it's a substance that acts directly on the brain, on the central nervous system.

Okay. Can you remember something else that we covered on this podcast that is also a psychoactive drug? Caffeine. Caffeine! Yeah, exactly. So alcohol has direct effects on our brain, both in the short and the long term, that are not only important to understand, but are also fascinating. As per usual, I'm not going to be able to cover it all. And alcohol affects a lot more of your body than just your brain, but for most of this episode, I'll be

focusing on the effects on the brain. I'll get in a little bit to some of the kind of long-term effects on other organ systems. So let's get into it. Here's how I'm going to break this down. First, I'm going to talk about the direct effects of alcohol in kind of the short term and how it produces what we all know of as drunkenness. And then we'll talk about one of my favorite parts, which is the dreaded aftermath, the hangover. Yeah. All right. And, To discuss that, we do have to get a little bit into the metabolism of alcohol, but I promise I'll keep it biochemistry light. And then, Erin, I want to hear from you about how long we've been giving ourselves hangovers.

And then at the end, we'll wrap it up with like the status of alcohol in the world today by at least a couple of measures that I have data on. All right? Okay. So alcohol, ethanol, it's freely absorbed across our GI tract. the same way that water is. So it can easily pass through any and all of our biological membranes, including, of course, our blood-brain barrier.

So after you drink a beer or a glass of wine or a quarantini, ethanol rapidly reaches peak concentrations in our bloodstream and tends to go first to areas of high blood flow, which includes our liver, where it causes lots of damage that we'll talk about later, our kidneys, and what it does in our kidneys is it interferes, is it interferes with water reabsorption. It does this by inhibiting the function of proteins that usually allow water to escape.

And so it functions as a diuretic. Why does it do that? Is it just sort of... Why does it do... The question of why, Erin, is when I'm never going to be able to answer in this episode. Fair warning. But it interacts with a specific protein called vasopressin.

and vasopressin normally allows aquaporins to go into our kidneys, but it basically inhibits the function of that in our kidneys. So it causes you to lose a whole bunch of water. Hence, you pee a lot. And then, of course, it also goes to our brain, which is full of blood flow for important reasons. So ethanol enters our central nervous system, and in truth, it acts on so many different receptors,

in a lot of ways that are very complex and we don't fully understand them despite loads of research. But what we do know is that a large part of the effect that ethanol has is on a specific receptor in our brain called our GABA receptors. And if you think in very basic terms of our brain as having both excitatory, like stimulatory and inhibitory pathways, excitatory ones making you alert and vigilant or whatever, and inhibitory ones being more sedating or more calming, which is an oversimplification. But what alcohol does is it binds indirectly to GABA receptors, which are inhibitory receptors,

and it makes these more active or more receptive to the effects of GABA. So what that does in practice is it makes us feel more calm. Okay. And it's a sedating drug. Is that how all sedatives work, like the basic mechanism? There are, so benzodiazepines are another class of drugs that are sedating that also act on the gabber receptors in a slightly different way. But there are lots of other sedating drugs that act on different receptors. Different pathways or receptors.

Okay. Yeah. I have a question about diuretics. Okay. Oh, gosh. Do diuretics sort of all function in the same way that alcohol does or, like, lead to the same, you know, water loss? You mean like diuretics, like other drugs that we have for diuretics? No, there are whole, like tons of different classes of diuretics that all act in different areas of the kidney on different ways.

I need to know more about diuretics. Oh, we could do a whole episode about diuretics. I'd love it. Okay. Okay. You know, what we can do is do an episode about heart failure and then we can talk a lot about diabetics. Oh. Oh.

Okay. Okay. Yeah. Anyways, back to alcohol. So it makes us feel more calm. It also makes us feel more happy because alcohol also serves to stimulate the dopamine pathways in our brain, which are our brain's innate reward system. Mm-hmm. Right.

So then. How do we generally feel after a glass or maybe two of wine? We feel more relaxed. We might feel a boost in our happiness. We might feel even euphoric or super chatty because of those effects of dopamine. We feel generally good. And then maybe a tequila shot sounds like a good idea. Friends, it is rarely a good idea.

And as our blood alcohol content increases, that feeling of relaxation progresses, it might progress to suppression of our anxiety. It might suppress our stress response. But at the same time, our central nervous system is also becoming more depressed. We aren't able to think as clearly. We might, through both central nervous system and also just GI-related effects, start having some nausea or vomiting. Our motor and our sensory systems can start to become in-pair.

and you lose especially that like motor coordination. And as that blood alcohol content continues to increase, our brain becomes flooded with ethanol, and then the blood flow to our brain is impaired, which can cause things like blurry vision, slurred speech, dizziness, confusion, eventually possible loss of consciousness, coma, and even death. can you put this in terms of like blood alcohol content or like number of drinks type thing which i know

varies because tolerance really varies person to person etc etc yeah so that question gets at a couple of different things both how much of the ethanol that you consume is absorbed and how quickly does it take effect as well as like what specific concentration of alcohol produces those specific effects And you're right, there isn't really a clear-cut answer because there's a lot of variability. The rate at which alcohol is absorbed across the GI tract varies a lot. For example, if you have a full stomach, then it's absorbed a lot more slowly. If it's an empty stomach, it's absorbed more quickly. And then you also have not only metabolic differences in how quickly you metabolize alcohol,

but also tolerance effects depending on how often you drink. in general though so we measure alcohol in your blood by blood alcohol concentration so you've heard like 0.08 percent is like the legal limit in the U.S. At concentrations below 0.08 percent in general you're not having as much of the motor and cognitive deficits. At concentrations above that especially approaching 0.1 percent that's when you have like sedation impaired motor and sensory once you get to like 0.3 to 0.4. or above, especially above 0.5%, that's when you can see acute alcohol toxicity or death. It's hard to say exactly how many drinks it takes. It really varies person to person.

Okay, so I feel like maybe this is just something that you hear in college, and that's like, oh, eat a full meal before you drink and you won't get drunk. And I always kind of thought, well, I think it's just you get drunk more slowly, or it affects you more slowly. or it affects you more slowly, but like is there actually a maximum at which like your body just can't absorb a certain amount of alcohol in a certain time period? And you'll like, you know what I mean? Yeah, it's a good question. It does seem to be the case that if you have a full stomach, it leads not only to slower absorption, but over time to lower blood alcohol concentrations. So part of that might be, and I'll get into this a little bit more in a minute, is that alcohol is methamptuble. tabalized by what's called zero order kinetics. So the rate of excretion is constant regardless of the

concentration. So it could just be that if you're absorbing it more slowly because of the full stomach, then you are excreting it at a rate that is such that when you're absorbing it slowly, you don't, your blood alcohol concentration doesn't rise as high. Right. You keep up with absorption. Exactly. Okay. Yeah. Interesting. Yeah. Eating does help. And as we can continue talking about, important the day after too, so let's talk about it. Yeah. Shall we move on to the biochemistry of a hangover? Perfect.

So to be eliminated from our bodies, alcohol has to be metabolized, which just means broken down. Eventually, it's broken all the way down into carbon dioxide and water. And at some point can be used for, like, actual energy production. But along the way, it's metabolized first into a top. toxic intermediate. So we already talked about the direct effects of alcohol. So now we get to talk about these toxic intermediates and the aftermath. So alcohol is metabolized first into a compound called acid aldehyde, which is toxic in a whole number of ways. It first induces

oxidative damage, both directly. And then as we'll continue talking about, it has a lot of other downstream effects as well. Alcohol dehydrogenase is the enzyme that breaks alcohol down into acid aldehyde. And while it's present in a lot of our body, primarily alcohol is metabolized in our liver, like over 90% of it. And so this is where acid aldehyde tends to build up, and that's why drinking alcohol can have such drastic impacts on our liver. Right. And result in things like cirrhosis, which is chronic liver damage. But since this intermediate is toxic, our body obviously wants to get rid of it as quickly as it can. So it further breaks it down via another enzyme called aldehyde dehydrogenase, right? And then it breaks it into acetate,

further breaks it down, et cetera, et cetera, et cetera. What's important to know about this metabolism of alcohol, what I think is so interesting, is that this process inadvertently, ends up interfering with a whole host of our normal metabolic processes, which explains some of the symptoms that you feel when you've been drinking alcohol, but also it explains a lot of the symptoms of a hangover, which anyone who's experienced a hangover knows these symptoms can last a long time and really make you feel like trash. So without getting into the weeds too much of the different biochemical cycles, let me just say this. We talked in our diabetes episode. about how, like, glucose is one of our main substrates that our body uses.

We talked a lot about it. But our cells have a lot of different complex cycles that they use to break down different compounds to create ATP for energy so that our cells can use them. And all of these different cycles are interdependent. They overlap with each other. And by overlap, what I mean is that these different metabolic pathways use a lot of the cofactors. And cofactors are substances that are necessary as part of a chemical reaction, but they aren't the actual parts of the chemical reaction. They're like helpers that you need for

this reaction to happen. This is like way flashback. So cell bio and it's kind of given me the hebi genes. I'm sorry. I'm trying to avoid saying like the TCA cycle. So let's get back to alcohol. The process by which alcohol is metabolized first into acid aldehyde and further and further all the way to like acetic acid, these steps of metabolism use up certain co-factors in our body and change the ratio of what's available for other essential cycles in our body. So what that looks like is a whole host of screw-ups in the way our body is supposed to do basic metabolism. Okay. So it's not alcohol directly, but it's the process of alcohol metabolism and the metabolites themselves that cause a lot of the symptoms that we know of as a hangover. So we can go through some specific examples if you want to. That's, yeah, I do. But that's really interesting because one of the ways I remember hearing hangovers described is sort of the result of stealing happiness from tomorrow. Yeah, that's kind of true.

So like you go out, you go drinking, you have lots of fun, and then you have used up the happiness that you like the ability to kind of have a good day the next day. That's so funny. Same as with cofactors. That's exactly what it is. You're using up your body's NAD plus, which is a happiness. Okay. Yeah. Yeah.

So we can go over some of the specifics. Okay. If you want to. Yeah. All right. Of course. Great. So one of the things that happens as a result of stealing these happiness cofactors is that the metabolism of alcohol ends up blocking the process of gluconeogenesis.

This is the process by which you make more glucose in your body in times when your glucose is low. So without the ability to do this, you end up with hypoglycemia, which we talked about in our diabetes episode, that, can make you feel shaky. It makes you feel super hungry, probably nauseous, weak, trembly. But the thing about this is, it's not always even a true hypoglycemia. It's what's called a relative hypoglycemia because you're not able to make glucose from what you already have available in your body because you're missing these cofactors. And on top of that, because of missing these cofactors, you're also not able to undergrateful. You're also not able to undergo the right kind of catabolism to use what you do have already. Wow. Water, water,

everywhere, nor any drop to drink. That's exactly what it is. The metabolism of alcohol, as well as some of the actions of alcohol itself on our brain, also uses up all of our body's glutamine stores. Glutamine is an amino acid, which is used to make proteins. It's also an essential neurotransmitter in our brain. So by using up all of our glutamine, it makes us feel very tired. And then as our body makes more and our glutamine can rebound, it can lead to things like tremulousness, anxiety, restlessness, things that we might see in like alcohol withdrawal syndrome. We already talked as well about how alcohol is a big diuretic. So then you likely are going to end up dehydrated, which might make you feel awful in and of itself, also give you things like a headache.

In the mid to longer term, the metabolism of alcohol also inhibits the breakdown of fatty acids, which means you have a bunch of fat, like little chunks of fat floating around. And your body then stores those in our liver, which causes further damage to your liver because of this inflammatory response to this fat. Interesting. So that is why you feel so cruddy with a hangover. It makes sense? Mm-hmm. Yeah.

So that's all of kind of the acute symptoms of alcohol and hangovers. Of course, it's important to talk about long-term exposure. Chronic high levels, especially, of alcohol use can lead to a lot of different health problems. And I'll just go through kind of the biggest ones, which we've kind of already touched on as well. cirrhosis, cirrhosis being chronic inflammation and eventual scarring of the liver, happens both because, like I said, of the fats that are deposited causing inflammation, as well as direct damage from both acid aldehyde and alcohol in the liver itself. In your brain, chronic alcohol use can also lead to a syndrome known as Wernicke-Korsikov syndrome.

Have you heard of this, Erin? No, I don't think so. So Wernicki Korsakov, it's actually two different syndromes that are kind of lumped together as one. It's Wernicke's encephalopathy, which is an acute and potentially fixable disorder, as well as a longer-term irreversible dementia that's known as Korsikov syndrome. Both of these are actually caused not by alcohol directly, but by a thiamine or a vitamin B1 deficiency. So this is a syndrome that can occur with no alcohol whatsoever. But today, because we like four to five flour and things like that, over 90% of cases tend to be associated with chronic long-term alcohol use.

And alcohol results in vitamin deficiencies. I can see your face that you're going to ask how. Uh-huh. Uh-huh. You got it. So alcohol use results in vitamin deficiencies, not just thiamine, but especially thiamine, in a few different ways. it can reduce overall absorption of our vitamins by just interfering with our gut.

The metabolism of alcohol uses up cofactors. We know that. That are essential in the recycling of thiamine as well as other vitamins as well. The effects of alcohol on our kidneys also cause us to lose thiamine more easily. So we're peeing more thiamine out. And then alcohol use also, in part because of its effect on the kidneys, affects our overall electrolyte balance, including magnesium, which is an important electrolyte and an essential co-factor in thionine utilization.

It really is all about the co-factors. It really is all about the co-factors. And then on top of that, alcohol itself and acid aldehyde both do cause chronic damage to our brain that can lead to generalized volume loss. So it does a lot of different things in a lot of different ways. Yeah. So I mentioned already that alcohol is excreted by what we call zero order kinetics. What that means is that no matter how much alcohol that you have in your system,

so even at very low concentrations or even at very high concentrations, the enzyme that breaks down alcohol, that alcohol dehydrogenase has such a strong affinity for ethanol. that it gets completely bound up. Like all of the ADH, the alcohol dehydrogenase, gets completely saturated with ethanol, even at really low concentrations. So it's working at its max from day one, right? Mm-hmm. But we know that tolerance exists.

And so one thing that it seems is that when alcohol use is chronic, it actually serves to upregulate a different type of alcohol metabolism. So it uses a completely different set of enzymes. And this is called the microsomal ethanol oxidating system. This is a separate enzyme in our liver. That's just basically another way that ethanol can be metabolized. Everyone does it at a low level. But in some people, or over time for some people,

this kind of gets upregulated as a bigger chunk of health. how much alcohol is metabolized, if that makes sense. Yeah. And what's really interesting is that along those lines, there's actually a lot of genetic variation in alcohol metabolism. Yeah, right. So there are certain alleles, certain genetic changes that have been identified that result essentially in an increase in that same system that gets upregulated with chronic use.

And so this means that some people just genetically, are much faster metabolizers of alcohol, which is so fascinating. It is interesting. And then there's the flip side of that. And not on the flip side. There's other genetic variants not in alcohol dehydrogenase, but in aldehyde dehydrogenase, a LDH, that downstream metabolism. And it makes that super slow.

What that leads to is a buildup, not of alcohol, but of acid aldehyde, the toxic intermediate. Yeah, it's not good. It's really not good. So that's why for some people, they have like one single drink and they end up flushed, nauseous, feeling terrible, just bodily feeling awful without even any of the cognitive effects that we attribute to drunkenness. It's like going straight to a hangover. Uh-huh. Right. So there's a lot of genetic and also just individual variation in how people metabolize alcohol.

Pretty cool, right? It's interesting, and I'm going to talk a little bit more about it in the history section. Oh, good. I can't wait. Yeah. So do you have any questions, Aaron? I mean, so I guess I have lots of questions. One has to do with sort of how either the role of genetics or the way that we metabolize alcohol, how that plays a role in addiction. And the other thing is also about like alcohol and people who are not yet adults, whether that means like exposure while a fetus or exposure while you're young. What are the effects of alcohol on you? Oh, great question. So I don't have a good answer to your first question about sort of genetic variation in sort of susceptibility to alcohol addiction.

Okay. That would be a really interesting topic that I just didn't have time to research with all of the other things. But, yeah, I feel like the genetics of addiction are really, really fascinating in general. And there is a very strong genetic component to alcohol use disorder. But to my knowledge, at least from what I found, I didn't see any specific genes that are necessarily related to it. Okay.

Like individual genes. So it's a lot of probably G by E, gene by environment interactions that seem to affect it. Right, of course. In terms of the effects of alcohol on the young, certainly anything that affects your central nervous system is going to have more drastic effects on people that are younger. Alcohol crosses the placenta freely the same way that it crosses our blood-brain barrier. So it's able to reach a developing fetus and to reach that fetus's central nervous system. We have very, very good data of the effects of moderate to high levels of alcohol use on the fetus, which produces a syndrome known as fetal alcohol syndrome,

which is a real constellation of a lot of different potential problems, ranging from mild cognitive deficits all the way up to more severe or even spontaneous pregnancy loss type complications. I think a thing that's important to point out is that while we have very, very, very clear data of the harms that can come from drinking moderate to heavy amounts of alcohol during pregnancy. Obviously, all of these studies are very difficult to do in humans for so many different reasons, and a lot of them are sort of epidemiological studies that are rife with things like recall bias, etc. But in general, the kind of consensus among public health agencies is that there is no evidence of a safe level of alcohol consumption during

pregnancy. There was a study that came out in 2017 that suggested, and it got a lot of press at the time, that like, oh, less than 32 grams a week, which is two alcoholic drinks, it was like two glasses of wine a week or something. There was only a modest risk of premature birth and small for gestational age babies. Both of those can carry serious downstream health problems, and I'm not sure how long that study actually followed those babies after birth. But other studies have also shown things like an increased risk of spontaneous pregnancy loss, but most of those were with five or more drinks per week. So we don't have a lot of good data for like smaller amounts of alcohol. But in general, the public health agencies both here in the U.S. and across the world take the stance of no level is known to be safe.

So is that I mean that's also sort of the same stance for just alcohol consumption generally right? I mean like you know I feel like every other week there's a study that's like oh a glass of red wine. Oh no, a beer. Oh no. It's actually you have to do like this very particular recipe. Yeah. It's interesting because if you look at sort of all cause mortality and especially cardiac mortality, there is a kind of J shaped curve where it seems like one to two drinks. a week might be a little bit protective in epidemiological studies against cardiac mortality. I think that in general, a lot of the public health thought is that there are so many known risks to alcohol that the maybe small evidence that there could be a maybe benefit to cardiac mortality is probably outweighed by all of the other risks, if that makes sense.

So there's not like super strong data. I don't think in general it's something that is recommended as a thing to keep you healthy for by any means. Right. Right. Yeah. That makes sense. But so that's pretty much the biology of alcohol, Aaron. This is a lot.

I have one more question. Oh, gosh. It has to do with hangovers. Okay. And so if we know what causes hangovers, like how do you. replenish co-factors besides just time. Time, Aaron. Yeah.

Did you read the paper? I found a paper that was just 18 pages of hangover cures. No. Oh, my gosh. I have nothing about hangovers in my history section. Okay, well, I will post a paper that's like 18 or more pages of just old-timey hangover cures. It's amazing.

Oh, my gosh. You would love it. Oh, I can't believe I did see that. Yeah, none of them are real. To actually treat a hangover, sleep is important because alcohol messes with your sleep cycles. And so even if you pass out, you're not getting quality sleep. Right. So sleep is important.

Drinking lots of water because you're dehydrated. Eating food because you know you're hypoglycemic. Ibuprofen or other medicines that are inhibitors of prostaglandin synthesis tend to have at least a modicum of evidence that there may be a little bit helpful. Like ibuprofen specifically, not acetaminophen. Right. So acetaminophen is Tylenol, which is, yeah, going to go to your liver. So you don't take that while you're drinking, please. Don't take ibuprofen while you're drinking either.

I'm talking about the next day. Yeah, yeah, yeah. There's also some thought that B vitamins, since those are cofactors for a lot of different forms of metabolism. If you replenish those levels, maybe. But yeah, none of those have like actual data. It's really just time. And also hair of the dog does not work. No, it does not work.

Yeah. Okay. Is that it? You have more questions? I think that's it for now. That was a lot. It was pretty long. Sorry.

So can you tell me how long have we had a hangover collectively? Oh boy. I can't wait. I will get started right after this break. Anyone who works long hours knows the routine. Wash, sanitize, repeat. By the end of the day, your hands feel like they've been through something. That's why O'Keefe's Working Hands hand cream is such a relief. It's a concentrated hand cream that is specifically designed to relieve extremely dry, cracked hands caused by constant handwashing and harsh conditions. Working hands creates a protective layer on the skin that locks in moisture. It's non-greasy, unscented, and absorbs quickly. A little goes along well. moisturization that lasts up to 48 hours. It's made for people whose hands take a beating at work, from health care and food service to salon, lab, and caregiving environments.

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Hello, hello, I'm Malcolm Gladwell, host of the podcast Smart Talks with IBM. I recently sat down with IBM's chairman and CEO, Arvin Krishna. And I asked him, how can companies use AI to its fullest potential to create smarter business? My one advice to that. Pick areas you can scale. Don't pick the shiny little toys on the side. For example. If anybody has more than 10% of what they had for customer service 10 years ago,

they're already five years behind it. If anybody is not using AI to make their developers who write software 30% more productive today, with the goal of being 70% more productive, Yeah. Wow. So we are not asking our clients to be the first experiment on it. We say you can leverage what we did. We're happy to bring out all our learnings, including what needs to change in the process, because the biggest change is not technology,

is getting people to accept that there's a different way to do things. To listen to the full conversation, visit IBM.com slash smart talks. Okay, the history of alcohol. Yes, all of it. Simple enough, right? And I'm going to try to not do the thing that we always do, which is apologize in advance for not including every tiny piece of information about the topic we're covering. Even though I'm like right now I'm actively resisting the urge to apologize.

I know. I do it every time, Erin. I know. It's really hard not to. And everyone knows the drill anyway, right? Like we're not experts. and this is not a comprehensive audio textbook on alcohol. It would be very challenging to do that.

And it would require like a whole team of people, not just two people. Two humans. Instead, I'm going to tell you what I am going to cover and hope that we all have fun along the way, even if I miss some things like here and there. And if you're left wanting more, that's great because curiosity is the best. and you can check out further reading for the topic on our website post for the episode where we include all our sources. And also there is no shortage of books about alcohol, you know, as like specific as like the history of bourbon in this one county and as broad as like the global history of alcohol. So there's anything you want.

Okay. So what am I going to cover about the history of alcohol? Basically, the way that I set this up is to first talk a bit about the evolutionary origins of alcohol metabolism or ethanol metabolism. So when did humans and other animals evolve this ability and how much does it vary across species? And then just kind of like play the hits in the history of intentional alcohol production by humans, starting all the way back at the beginning thousands of years ago and ending at today or at least like the last few decades. decades or so because yeah. Yeah. There's a lot there.

Let's get started. Aaron, you answered how humans can metabolize ethanol and what it does to us and all that good and bad stuff. But I want to get at the why of this. Like why we possesses ability, where did it come from and when did it come from under what circumstances? And then I might dabble a bit in another why, like why we get drunk. What are the benefits and drawbacks of alcohol consumption from an evolutionary perspective?

Do the pros outweigh the cons? But first things first. Many, many organisms possess the ability to metabolize ethanol. But humans are somewhat unique in that we possess a particular form of that alcohol dehydrogenase gene. And it's specifically for, if you're interested, the alcohol dehydrogenase-4 enzyme. And this form, this mutated form, allows us to metabolize alcohol much more efficiently than most other animals, like 40 times more efficiently, as compared to the non-mutated version. I did not know it was that big of a difference. Yeah, it's really big.

And I say somewhat unique, because we aren't the only animals to have this mutation. Chimpanzees, bonobos, and gorillas also have the same type of mutations. at the same spot in that gene for ADHD4, alcohol dehydrogenase. From this point on, I'm just going to call it alcohol dehydrogenase and acknowledge freely that it is just one of the enzymes, okay? Not all of them. But there are other animals that also have the same type of mutation at that same spot, and that is the large fruit bat, the common vampire bat, i.is, and koalas. What? That's such a random assortment. Well, or is it? Oh. And then there are a couple other animals, a couple other species of bats that also have a mutation in that gene, but not the same exact kind. So we also don't really know, like beyond chimpanzees, bonobos and gorillas, we're not really sure, you know, physiologically, vampire bats, a large fruit bat, I-eyes, koalas, they have like different, um, gastrointestinal systems compared to like great apes, right? And so whether the function of that

mutated alcohol dehydrogenase is the same in those as it is in these, you know, great apes, we don't know for sure. But there's also like some hints that it might be at least somewhat similar. Okay. Basically, there's a lot that we don't know about alcohol metabolism in other species. But what is the whole point of this section? Well, it's, okay, it's one thing for a mutation to occur. Like it happens all the time, but it's another for it to stick around. In order for that to happen, it has to be a useful mutation, generally speaking, could just be, you know, drift, whatever. But it turns out that this mutation in the gene for alcohol dehydrogenase appeared in the ancestor of humans, chimpanzees, and gorillas about 10 million years ago.

So that's when this mutation, this new enhanced form first appeared. And that's right around the same time that our primate ancestor started venturing down onto the ground from the trees, becoming more terrestrial than arboreal. On the ground, they would have found a great food source, fallen and fermenting fruit. That's right. That's right. Okay, yeah. Uh-huh. And some of this fruit would have contained ethanol concentrations as high as like 8.1%. Wow.

Mm-hmm. This new mutation, which helps us metabolize ethanol more efficiently, it would have been a big advantage in utilizing this new food source and also not getting too impaired by it and getting picked off by predators, or, you know, your neighbor. So it makes sense that it was retained and then spread throughout subsequent generations all the way down to modern humans. The other animals that have this mutation, chimpanzees, bonobos, gorillas, eye-eyes, etc., these are animals also known to forage extensively on fruit and nectar, which may also be fermented and may also contain ethanol. So it seems as though diet plays a big role in the evolution of these genes for the metabolism of ethanol,

why we can process it more efficiently, and why some animals have actually lost the ability altogether. So there's a recent study from 2020 by Janniak at all that showed that the gene for ADHD 4, for this alcohol dehydrogenase 4 enzyme, is non-functional in some animal species, meaning that it was once there and it once worked. Right. And then it accumulated at least one mutation that would have made it stop working. Huh. Yeah. Interesting. And it turns out that there's a pattern among these animals with the non-working alcohol dehydrogenase. They don't really have nectar or fruit in their diets.

And so it wouldn't have been that important to keep that functional gene. So relax selection and boom, some of them just long. lost it. Okay. So I feel like I've already gotten a bit into the weeds here, but I wanted to bring this up because I think it's an absolutely fascinating look, not just at the evolutionary origins of the way humans metabolize dietary ethanol, but also why this ability might vary across the animal kingdom. Like, what are you eating? And how is that affecting your physiology in the way you metabolize certain compounds. And I also should end this part with a caveat that is that this is just looking at one enzyme

for a dietary ethanol metabolism. Granted, it is the first enzyme that would encounter ethanol after it's consumed because it's the one that's like in your, you know, the first part of your gastrointestinal tract and whatever. And that there are many other enzymes involved that are part of this process and that metabolize other forms of alcohol as well, such as some that would be encountered by, like, consuming certain plant leaves, for example. All right. So we've now established the likely origin story of our enhanced ability to metabolize alcohol and to some degree why it gave us

an evolutionary advantage. Because it allowed us to use a new food source. Firmutation can actually increase the nutritional value of things, make it like more bio. available, I guess. So drink your kombucha, that's what you're trying to say. And also, don't forget that it can decrease the prevalence of harmful pathogens and parasites. Yeah, that's pretty major. It's pretty major. And that's something that became especially more important later on.

The importance of dietary ethanol to humans and other primates is also maybe illustrated by just how sensitive we are to the smell of it. a smell that signaled to our evolutionary ancestors, hey, here's some ripe fruit to eat, here's some good food here. Interesting. Like, it's interesting to think about what we're more sensitive to in terms of smell, in terms of, like, taste. Yeah. All of these things might have roots.

Yeah. Huh. And let's also not forget that we're sensitive to the effects that it has on our bodies. It makes us drunk. It makes us feel good. it triggers these reward systems in our brains that evolve to encourage adaptive behavior. Like, hey, dietary ethanol is a good food source. Keep seeking it out. And this hijacking of our reward systems, like, it might have worked out great when the sources of alcohol were limited to the, you know,

piles of fermenting fruit on the forest floor. Right. But then, once humans began to actually intentionally produce alcohol, some more of the downsides began to appear. Right. And there still seems to be some debate on when this was, like when humans began to first intentionally produce alcohol. It's like this question of chicken or egg, but instead of chicken or egg, it's what came first beer or bread. Did humans begin to settle in large groups and domesticate grains, aka the agricultural

Revolution and then noticed that rain-soaked grains produced a fermented alcoholic beverage? Hmm. Or did they settle in large groups and domesticate grains so they could produce alcohol? Huh. Over the past few decades, the second hypothesis, the beer before bread won, it's become increasingly popular. Rather than the agricultural revolution providing the means and locations for large gatherings, for which alcohol might have been produced, those might have led to the agriculture.

the agricultural revolution. Huh. So people started to settle because of the large gatherings, rather than being able to settle because of agriculture. They started to like get together, hang out more in groups, eat fermented fruit and be like, we should be able to make more of this. Like, why don't we try and do it ourselves here? Let's plant some barley.

Yeah. What? Yeah. I mean, yeah. It is like there is some support. from archaeological evidence, such as what we see is Gobeckley-Tepe, a super old, like 11,000 years old archaeological site in what's now Turkey. It's really cool.

You should definitely read more about it. I am fascinated by it. And at the site, which was constructed at the very beginning of the agricultural revolution, there's evidence of big fermentation vats and storage basins used to brew beer. And that's not that surprising, except for the fact that some archaeologists believe that this was not a continually occupied site, but more of a site that, like, groups of nomadic hunter-gatherers would congregate at during certain times. So it was, like, sort of a meeting place. Yeah. Interesting. I will say that more recently, the supposed, like, transient use of this site has been called into question, and some people are saying, well, maybe it was continually occupied.

Okay. All right. But there's still more. In the Fertile Crescent, some of the earliest archaeological sites show tools and grains that are more in line with beer making than bread making. Okay. Personally, this is my opinion. I feel like it doesn't necessarily have to be one than the other.

Right. Why can't humans have begun to settle in large groups and domesticate grains for both beer and bread? Right. And also, like, what do you do with the grains when you're done fermenting them? You make bread. So you do both. You do both. Waste not want not, Aaron.

Exactly. But anyway, the point that I'm trying to make here is that humans around the globe have been intentionally making alcohol for a very long time. Yeah. Like they saw this, they tasted it, they recognized it, and said, I want to be able to have this all the time. Mm-hmm. Mm-hmm. And to underline that, here are some examples. Yes.

There's a 20,000-year-old carving from southwest France that shows a woman, possibly a fertility goddess, drinking out of a horn. Maybe it's been speculated it was some fermented beverage. Maybe. It's thought that some strains of yeast associated with wine and sake production might have been domesticated over 12,000 years ago. Whoa. Which is really cool. domestication now. I know. Let me say, wow. Oh, yeah. The oldest physical evidence of an alcoholic beverage comes from the Yellow River Valley of China from around 7,000 BCE. And it was made from

like wild grapes, hawthorn fruit, rice and honey. Grapes were domesticated in what is now Georgia, from around 7,000 to 6,000 BCE. In what is now Iran, there is evidence of grape wines and ceramics from 5,500 to 5,000 BCE. In Armenia, there's an ancient cave site that seems to have been a winery complete with grape stomping basins, presses, fermentation vats, storage jars, drinking vessels. The oldest surviving recipe is a recipe for beer from 3,400 BCE. Fascinating, Erin. The oldest preserved liquid alcohol was found in China and dates back to 1900 BCE.

And there are references to alcohol in our oldest surviving literary document, the epic of Gilgamesh from 1800 BCE, and in our oldest law document, Hammurabi's Code from 1770 BCE, which regulated the strength and price of beer and forbade women from drinking it. Oh, okay, a lot of woes on that. Also, we're going like way back further than the Eber's papyrus. Is that where you're telling me here? Oh, yeah. I mean, I'm sure that it's in the Iber's papyrs. Shame on me for not finding it explicitly. Wow. It's, yeah, I mean, the evidence for, like, early and thoughtful production and consumption of alcohol is, like, vast and varied. As are the ingredients used in fermentation. It's so interesting to me that you brought up grapes so early. Like, grape, people were like, hey, grapes, grapes,

Graves make really good alcohol from day one. That's so interesting. It's really interesting. And I think I don't know much about the domestication process of grapes, but grapes for like just one of many ingredients that people use. And I'll definitely go into some more of these or at least like a list of examples of things that people use later on. Okay. So now we're in the agricultural revolution. We're there. I'm taking us there. And so with this period of time of huge change, alcohol took on many other important roles, not just as a food source, but also as a medicine or a good to trade, as a component of religious ritual or a celebration. You know, Dionysus, Jesus. There were many gods or religious figures associated with. with like certain alcoholic beverages, wine in particular.

Yeah. But the availability of alcohol in large quantities also revealed, of course, it's dark side. In many ways, these structured rituals or ceremonies at which alcohol was consumed helped to regulate consumption. Like they created these boundaries between what was acceptable drinking and what was too much. They weren't like free for all. It was very like, you know, you want to be respectful of the gods. You want to commune with.

them in a way that is like the right way. Drinking too much was seen to have negative health consequences, to lead to alcohol dependence, to lead to accidents, and at the very least, lead to negative social interactions. For about as long as humans have been making alcohol intentionally, we have also been issuing proclamations against it. The most famous is probably, of course, the prohibition of alcohol in Islam. which began in the 7th century CE, but even before then, China attempted to ban alcohol in the second century BCE. And it wasn't necessarily all or nothing. Like in many places, alcohol consumption

in moderation was fine, but excessive drinking was looked down upon. Like, for example, there's an inscription on a stadium in ancient Greece that forbids spectators from bringing wine into the arena, which like it cracks me up because I'm like that is still on like every stadium, every concert hall, every whatever. You can't bring your own. Oh my goodness. Yep. Yeah, I wonder if they sold it for like, you know.

Of course they sold it. $15 for like three ounces of wine. Oh, my goodness. Humans have long recognized the cost of alcohol consumption, even if we've been able to quantify it or like understand the nuances of it only you know more recently and the costs are substantial. Aaron, you went over a lot of them both in the short term and the long term. And like you said, there's like most public health officials or groups will conclude that there is no real safe level of alcohol, no tablespoon amount of red wine that's going to make us like live longer. Right. So that

begs the question, maybe, why do we drink it? And maybe not that so much as why haven't we evolved to dislike it to undo that pleasure center hijacking? And we kind of have, actually. So, Erin, you talked a little bit about ALDH, aldehyde dehydrogenase that causes this build up these like immediate negative effects of, you know, like a hangover immediately. This buildup of acid aldehyde with these symptoms of facial flushing, hives, nausea, heart palpitations, difficulty breathing, et cetera, et cetera. Basically, it makes drinking alcohol extremely unpleasant. Right. Some people speculate that this mutation, which evolved independently in parts of East Asia, the Middle East and Europe, may have evolved in response to the increase in alcohol

consumption as a way of curbing the negative effects of alcohol. So looking at one of the evolution events, it originated between 7,000 to 10,000 years ago in East Asia, which is around the time that rice-based agriculture was spreading, and thus the availability of rice wine. So is this a defense mechanism against drinking too much? It's not clear. Yeah. If it is, we might expect it to be more widespread than it is if it confers such a strong selective advantage. And other researchers think that it might protect against fungal poisoning.

And like the alcohol is just a side effect of that. Yeah. And especially the fungal strains that would have affected, you know, stored grains. Or it might protect against tuberculosis. I don't know. But I think the other thing to consider is how we're looking at this equation of the pros and cons of alcohol consumption. In the ancestors of humans, the advantages were clear. Like, I've gone over them, right?

But did the ability to metabolize alcohol outlive its usefulness? Was it all just backfiring and hijacking after the agricultural revolution? The author of one of the books I read for this episode says no. that while there are clear disadvantages to the consumption of alcohol in an evolutionary sense, there are also reasons why it would have been selectively advantageous, even like after or during the agricultural revolution. For a long time, probably at least since humans have been settling in large groups, the primary adaptive challenge that humans have faced is not the environment and overcoming the environment,

but it's other humans. Right. It's everything we talk about in this podcast. Uh-huh. And like from a more social standpoint, like humans don't just need food, shelter, and water to survive. We've evolved to exist in groups where social cooperation, creativity, and tolerance and trust of non-relatives is necessary. The author of this book suggests that alcohol in moderation can help with those things. Quote, by enhancing creativity, dampening stress, facilitating social contact, enhancing trust and bonding,

forging group identity, and reinforcing social rules and hierarchy, intoxicants have played a crucial role in allowing hunting and gathering humans to enter into the hive life of agricultural villages, towns, and cities. It does make you more sociable. It does. So I bring this up, not because I necessarily agree. or disagree with it. But I think it's interesting food for thought or beer for thought. But I also think it shows that it's important to consider how the pros and cons equation of alcohol is specific

to a time and place and even to an individual when you're talking about it. Or I also have to say, maybe it's not as complicated as all that. This book had a very adaptationist perspective on the consumption of alcohol where like there has to be some evolutionary reason for it some way it increased our ability to survive and reproduce just beyond the fact that we like the way we feel when we drink it yeah um maybe as my younger sister would say it's not that deep i mean maybe the reason human's drink alcohol is just because we like it yeah and that's reason enough for it to have persisted for so so long. Definitely. Yeah. Yeah. It makes you feel good, literally. Yeah, exactly. Okay. Evolution talk over. Do you want to hear a very general history of alcohol? Always. Okay. Where did I leave off? So I've already covered some of the

archaeological and historical evidence of early alcohol consumption and production around the world. And I think that it shows not only how important alcohol was to many cultures, but also how creative humans are at coming up with new ways to make it. For instance, in the Orkney Islands, people included oats and barley with some additional flavors and maybe a light hallucinogen or two to make a kind of beer. Spice it up. In Tasmania, sap from a gum tree was fermented, and what is now Victoria and Southeast Australia, People mixed flowers, honey, and gum into a liquor.

In parts of Africa, people made banana beer and palm wine, which was also made in parts of South Asia. In Mexico, people made pulke from the fermented sap of the agave plant. And in Southeast Asia, people made tapai from fermented cassava. And of course, there was wine and beer and mead, made in many, many different places. Much of the very early history of alcohol is a bit like guesswork, but starting around 3,000 BCE and on is when our knowledge gets a bit more refined. And this is when we see the spread of technology for alcohol production along trade and

exploration routes. Wine-making knowledge and technology, for instance, seems to have originated in Western Asia, like modern-day Eastern Turkey, Eastern Iraq, northwestern Iraq, and northwestern Iraq. and then was brought to the Eastern Mediterranean and Egypt and then on to Crete, Greece, and southern Italy before arriving to the rest of Europe around 2,000 years ago. Helped along after that point very much by the spread of Christianity, which directly led to the spread of wine-making technology throughout the Western Roman Empire. Beer production, on the other hand, seems to have begun simulmonary.

in many different places, such as Egypt and Scotland. In ancient Egypt, wine-making technology seems to have been well-integrated into the culture, with production seriously ramped up. In 1000 BC, there's a list of 513 vineyards owned by temples, mostly in the Nile Delta. Wow. Yeah, it's like full-on production scale type stuff. Wow. And there are other writings from ancient Egypt.

showing that beer was a common form of payment, especially for the lower classes. And from the beginning, there seems to have been, in many wine and beer-drinking cultures, a class structure to these drinks. The wealthy and elite drank wine, the poorer drank beer, and the poorest drank water. The inherent greater value placed on wine does make sense in some ways. There was a shorter growing season. it couldn't be produced in the same quantities as beer, and it kept better than beer, which was important in long-distance trading. And these qualities led wine to be scarcer and thus more valuable than beer, which is one of the reasons why wine was included in rituals and ceremonies more often than beer, and why it was written about, like, we have more ancient writings, it seems like, of wine than we do, or references to wine than we do of beer.

That makes a lot of sense, actually. Yeah. And it also led to a class division between these drinks, one that we'll see time and time again throughout history. Beer was cheap. It was consumed by everyone, but wine was consumed only by those who could afford it. This attitude carried over into ancient Greece and Rome, where the climate was more suitable for grape growing. And beer was seen as like the drink of barbarians coming from like, those northern Germanic tribes that, you know, they couldn't grow wine up there, so they were clearly not cultured.

Goodness. Yeah. Wine production turned into like a full-on industry in Greece, even more so than it was in Egypt. And by 400 to 300 BCE, it took its place alongside olive oil and grain as one of the big three products of economy and commerce in the Mediterranean. In addition to transporting enormous quantities of wine in amphora's, and I mean enormous. So there's one shipwreck I read about that contains 10,000 amphora's, which is about 300,000 liters of wine. Oh, yeah, or about 400,000 modern wine bottles. Whoa.

Uh-huh. Yeah. And ancient Greece also held sympositions. where wine was consumed in moderation with strict rules. The word symposium actually means fellow drinker or drinking together. I did not know that. Yeah. And it was first used for these wine parties attended by upper and middle class men

from which women were excluded except to serve. Uh-huh. And boy, does this echo throughout history. I bet. Uh-huh. In many cultures throughout history, there are laws that deal in some way with restricting women from drinking alcohol, usually on the grounds that women who drink alcohol will commit adultery or be sexually promiscuous or whatever. In ancient Rome, there was a law that allowed a man to divorce his wife if she had been drinking. And alcohol consumption by women could also be punishable by death, which, Which is what happened to one woman, death via starvation in her case, who had been caught, not drinking, but just caught with the keys to the wine cellar. Oh, my goodness gracious. In the early Middle Ages in Europe, women in a household were the ones doing the brewing primarily.

That's why you hear the term like ale wives or brewsters. and so it would be like beer made at each house, right? Each household had their beer. But this changed starting in the 1400s, when women were essentially excluded from making beer as beer began to be made in commercial production facilities rather than an individual households as cities grew. Right. Like once it became a job rather than a household job.

Sure. Right. Yeah. Commercial brewing was regulated and required. acquired licenses, which women were forbidden from applying for. And this also marked the start of taverns. The first tavern license in London was actually in 1189. It's just like really old. But also women were forbidden from entering taverns as well for the most part. And these shifts to exclude women from beer production, they weren't just accidents of history, like a natural consequence,

but intentional, like, misogynistic exclusion, which is pretty easily seen in the depictions from this time showing women brewers as dishonest and unhygienic and women who drink in taverns as immoral. Of course. I mean, and this whole thing gets repeated again in Europe in the 1500s or so when distillation began to be widespread with women starting small-scale distilleries and then being shoved aside because they were forbidden to have licenses. But that's getting a bit ahead of things.

The Middle Ages in Europe led to an increase in beer and wine-making technology, a shift towards commercial production of these alcoholic beverages, and a big growth in long-distance trade as the preservation of wine and beer improved, for example, through the addition of hops to ale. All of these things marked a shift, where alcohol had moved beyond just being something reserved for rituals. And the huge spread of Christianity had certainly cemented wine as a sacred part of ritual by this point, or for just personal household consumption.

Alcohol at this point was now a key part of the economy. Alcohol production and consumption began to be taxed, and those taxes funded many a government. and the growth of cities and trade also led to a larger consumer market where variety was demanded. People wanted to choose what they drank, what vintage, from what region, and some places began to specialize in this. They began to be known for their wine or beer. And then distilled spirits entered the picture. I'm excited for this.

Distillation is a fairly old concept with fairly old technology. Experimental distillation was practiced in ancient China, India, Egypt, Mesopotamia, and Greece, with the technology most probably originating in the area around the border between modern Pakistan and India. But it wasn't really until the 13th century in China and the 16th through the 18th centuries in Europe that it became widespread. Brandy, distilled from wine, was the first spirit produced in large quantities in Europe, and then there was whiskey, gin, vodka, and others that followed. Production of distilled spirits became especially popular in places where the climate had prohibited growing grapes for wine. So, for instance, vodka, meaning little water, was developed in northeastern Europe,

in what is now parts of Russia, Poland, Belarus, and Ukraine. Rum, on the other hand, which was not the first liquor made from sugar cane. There were earlier ones in China and India. Rum was made in the sugar plantations in British and French colonies in the Caribbean by distilling molasses, which had increased in availability due to the huge numbers of people they were enslaving. This rum would then be used in trade, and this is where distilled spirits absolutely were far superior. to wine or beer for long-distance travel. Right.

And rum would also be added to water barrels on boats, with each member of the crew getting a ration of rum, which is sort of how like sailors and pirates around this time became to be so associated with the drink. And contrary to popular belief, the Puritans drank their fair share of alcohol. I just wanted to, mostly I bring this up because I wanted to include these numbers

is just a visualization of how much alcohol people brought with them on journeys. Okay. On the Puritan ship Arbella, which carried around 700 people from England to Massachusetts in 1630, there were 10,000 gallons of wine, 42 tons of beer, 14 tons of water, and 12 gallons of brandy. Oh, my goodness. Yeah. Yes. The introduction of distilled liquors was kind of huge and it really changed the way people interacted with alcohol. Historically, beer and wine averaged maybe 2 to 4% or 6 to 12% respectively. It's actually much more alcoholic nowadays. Like your standard beer or wine is more alcoholic than they used to be. But does. Distilled spirits, like, they can be incredibly alcoholic. Right.

Right. I mean, I would say the range was typically 20% to 100%, like just pure ethanol. Mm-hmm. And this was an amount of ethanol in any distilled spirit far beyond what our primate ancestors had ever encountered. Oh, my goodness. Yeah. And some people, like, use that to their advantage. The role of alcohol in colonialism is obviously deserving of much more attention than I can give it here,

but I do want to mention some of the ways that European colonizers used alcohol to subjugate and control the people whose lands they invaded. Generally speaking, most of the places that Europeans sought out to colonize already had a relationship with alcohol. Like alcohol, like I said, had almost a global distribution by this point. with one notable exception in North America where fermented beverages were less common, although not entirely absent, and rituals did not typically include alcohol, but that's painting with a very broad brush, and there are exceptions to that. But when Europeans invaded those places, whether they had a relationship with alcohol or not, they didn't drink the local fair, but rather they just drank the alcohol that they brought with them, wine, beer, spirits. And when they set up

permanent settlements there, they often planted vineyards or built breweries to make beer and wine for trade, for religious ceremonies, because most colonizers practice Christianity, and to just drink themselves. But it wasn't drink and let drink. It was, let's ban all of the local drinks because they weren't mentioned in the Bible. Oh, that didn't work? Okay. Well, let's just tax only those drinks instead. Colonizers also used alcohol as a currency or as payment for workers with the intention of dulling the impact of horrific working and living conditions and keeping them in a state of subordination. It was a weapon. Like alcohol was a weapon, a tool of colonization. In North America, colonizers created and spread the stereotype of the, quote, drunken Indian, which was used to

exclude and undermine Native Americans from any discussions of government policies or treaties that affected them, and was then used as justification to prohibit the sale of alcohol and guns to Native Americans 28 years before the 1920 legislation that led to the U.S. wide alcohol prohibition. and this specific prohibition wasn't repealed until 1953, which is 20 years after nationwide prohibition ended. I'm sorry. Yeah. And like similar things just like that happened in Canada,

but with slightly different time frames. Hmm. Mm-hmm. Which brings me to the last part of the history of alcohol I'm going to cover, also not in any great detail. Prohibition. Specifically, prohibition in the U.S. Don't get too excited. There's like not that much detail. I'm so sorry. Like I mentioned a long time ago in this episode, people have been trying to ban or limit the use of alcohol for about as long as we've been making it, with some bans or restrictions more effective than others. And I'm going to focus primarily on the

trend towards prohibition that began in the late 1700s, early 1800s, and then like, you know, culminated in the early 20th century in places like the U.S., Russia, Mexico, Canada, Belgium, Japan, and Finland, among others. It was like surprisingly widespread, more than I had realized. Starting around this time, starting in the late 1700s, morality around alcohol began to change. possibly due to the increasing availability of safe drinking alternatives such as tea or coffee, see our caffeine episode, and also the growth of distilled spirits, which was seen by many as like a negative consequence or like a negative thing. The gin craze in parts of England, which is like a thing that happened, took place between 1700 and 1750. This may have had something to do with it, but many accounts are super exaggerated and probably

just like an example of moral panic. But essentially what happened was that gin, like to men by gin, I mean all grain-based alcohol, not just juniper flavored. It increased in popularity in England from around 1700 to 1750 following a brandy shortage. And this led to people saying that women were unable to resist the call of gin. and that they were leading their unborn children to be addicted and that, you know, it was a lot of, oh, gin is disrupting family life and the father has to care for the children. Crime and immorality are on the rise, et cetera, et cetera. Overall, the gin craze seems to be more of like a class and gender war, which is not that surprising, considering how drinking had long been portrayed.

If you were poor, it was a criminal issue. If you were rich, it was a moral failing, but don't worry, all is forgiven. Tomorrow is a new day. These class distinctions around drinking and moral panic about alcohol consumption by women sort of like fed into each other, especially as industrialization meant denser populations in cities and a larger working class, both of which alarmed the wealthier classes who wanted to shut down the bars and taverns and public houses that were frequented by the working class, which the wealthier classes saw as the breeding grounds for criminality,

especially like the consumption of distilled spirits playing this big, you know, scary role. And the consumption of distilled spirits did massively increase. Like I said, it changed the relationship between humans and alcohol. So over the 1800s, for example, in Paris, although this trend is repeated in many other places, per capita consumption of pure alcohol from spirits rose from 2.9 liters in the early 1800s to 5.1 liters in the 1840s to 9.1 liters in the late 1800s. So that's like if you just take what they were drinking and then calculate the pure alcohol concentration of it. Okay.

With the introduction of distilled spirits, there was a lot of like, okay, this is scary. too much drinking, but alcohol is here. It's been such a part of our lives, maybe drink in moderation. And that was sort of the temperance movement. That's what it started out as, just drink in moderation and, you know, try not to overconsume. This gained a lot of traction in the second half of the 1800s with a push to replace alcohol with like tea or coffee or hot chocolate or water. And then starting in like the early 90s, the early 90s, and then starting in like the early 1900s, it turned into just prohibition, no alcohol, period. Eugenicist took up the cause, kind of, by listing alcoholism, which was first used as a term in 1849 by Swedish physician

Magnus Huss. They listed alcoholism as an undesirable trait that shouldn't be passed on to offspring. Uh-huh. It's always. I mean, yeah, I know. Always. There's always a tie to eugenics. And morality statistics were used to support the claims of anti-alcohol writers. Morality statistics? Uh-huh. Okay. Yeah, I know, I know. A big turning point came in World War I.

During that time, there was a change in the gender balance of some pubs, where women who were increasingly joining the workforce began to go. They began to, like, actually, you know, frequent these bars. and taverns and pubs. And this led, of course, to increased regulations on drinking and fewer operating hours. I read a quote in one of the books for this episode. It was something like men have always historically been anxious about the consumption of alcohol by women, which I think is like a very valid statement.

So interesting. Alcohol was viewed also during this time as weakening the soldiers and the morale of those at home. By 1916, 45 U.S. states had enacted prohibition statutes. The social cause of prohibition had been turned into a political one as politicians realized how strongly people felt about the issue, like strong enough to get them on their side to vote. Yeah. And on January 1st, 1920, the east. 18th Amendment took effect, which banned the production, sale, transportation, and importation

of alcohol for beverage purposes. And if you want to know more about that part of it, there's a whole Ken Burns' five-and-a-half-hour documentary on prohibition in the U.S., which I did not watch, but I want to. But from the research I did, it seems that the long and short of it, this period of prohibition, And it didn't actually seem to slow drinking rates all that much. But what it did seem to do was maybe normalize social and public drinking, which had been under attack for the preceding decades as the temperance movement and prohibition movement sort of ramped up.

And it also made drinking less gendered with more women attending speakeas than they had attended bars in the years before prohibition. There was also an increase in unsafe alcohol production and consumption since there was no regulatory oversight to ensure that people weren't drinking just like methanol rather than ethanol, for instance. Yeah, big deal. Mm-hmm. And 13 years later, it was repealed by Franklin Delano Roosevelt, FDR, largely because of a need for tax revenue, which grew actually incredibly. was like very a big source of tax revenue in the years after. And FDR ran on a repeal platform, still a political issue back then, and he won pretty

handedly, probably in part because of the way people had come to see prohibition, which was as an unwelcome intrusion into the private lives of U.S. citizens. most countries that attempted some form of prohibition or other did so in a fairly short window of time from around 1914 to 1933 with most never making it off the ground or ending up being repealed showing how difficult or even impossible it is to ban any commodity or service for which there is significant consumer demand and that often regulation and education and o'clock oversight might be more helpful than anything? I don't know. Yeah. It feels ridiculous that I am going to try to sum up the rest of the 20th century in alcohol in like two sentences, but that's just how big the history is. Yeah.

Since Prohibition, our relationship with alcohol and our understanding of it has changed, like, quite a bit. Yes, our good old friend, Louis Pasteur, discovered the process. of fermentation in the mid-1800s, which kicked off germ theory. But it wasn't until the 1940s that we understood the exact mechanism of fermentation, which allowed for quantification of blood alcohol content and more specific guidelines for what could be considered, you know, quote, safe consumption, question mark. Minimum drinking age was instituted in some places. attitudes towards alcohol on both individual and cultural levels became more nuanced as we gained a better

handle on what it does to our bodies, to our health, to our relationships with each other. Alcohol use disorder has been increasingly part of the discussion. Alcoholics Anonymous was first founded in 1935 and the stigma surrounding not drinking for whatever reason, you choose has also lessened somewhat, although still like kind of a long way to go there. When someone says, oh, I don't drink alcohol, and someone just goes, why? Why don't you drink alcohol? Come on, have you tried it before, you should try it. Like, maybe don't do that. Alcohol is a complicated subject. The biology is complicated, the history is complicated, our feelings about it are complicated. Yeah. And I'm sure that the current status,

is also complicated. Yeah. So, Aaron, what's happening with alcohol today? Oh, let's try and find out at least right after this break. So we'll just go over, I don't know, maybe the worst of it at first and then try and end on a semi-higher note. I don't know. Let's see what we can do here, Aaron. Okay.

Okay. So looking first at the U.S., in a paper from 2019, I found that between 2006 and 2010, so this is kind of old data still, the annual number of alcohol-associated deaths in the United States. So this encompasses anything from things like drunk driving or accidents where alcohol is involved, but also things like cirrhosis or. more chronic causes of alcohol associated death, et cetera, just any kind of alcohol associated death in the U.S. was about 88,000 a year, which represents almost 10% of all deaths in the United States. Wow. Yeah. That's a lot higher than I realized. Yeah. In 2010, and remember that costs in the U.S. have to be taken with a grain of salt, but the estimated alcohol-related costs in the United States were almost $250 billion, 77% of which were attributable to binge drinking.

Okay. Yeah, we didn't really talk about binge drinking. Yeah, but that, yeah, we didn't. Binge drinking is very bad. If we take a broader perspective and look worldwide, worldwide, according to the World Health Organization, about 3 million deaths every year result from harmful use of alcohol, which worldwide represents 5.3% of all deaths. Wow. And overall, about 5.1% of the global burden of disease and injury,

So the disability-adjusted life years measure is attributable to alcohol, which is way more than I would ever have guessed. And what is important is that if you actually look back a little bit further, there's a paper from 2004 from the World Health Organization because that data that I just said is from 2018. But a 2004 paper estimated that 1.5% of global deaths were attributable to alcohol and 3.5% of disability. adjusted life years were associated with alcohol. So that's a huge change. Yeah, what's happening? Yeah, that's a good question. I don't have the answer to that. Is it better reporting where we're getting better at identifying not just acute but also chronic causes that are associated with alcohol? Is it better awareness of the types of deaths that we might be contributing to alcohol? Or is it because alcohol use is increasing? I don't have a good answer for it, quite honestly.

Hmm. But... Interesting. It is interesting. And so you mentioned at the end of your history section, Aaron, alcohol use disorder. So the DSM-5, which I think that we've talked about on this podcast before, right? I think so. I think a long time ago. A long time ago. The DSM-5 is in the United States, the manual of psychiatric diagnoses. It encompasses very specific criteria on how to diagnose a whole number of psychiatric diagnoses, including what is now called alcohol use disorder.

And I won't go through the very specific criteria, but essentially they all tend to revolve around things like trying to cut down on drinking and not being able to, or taking in alcohol in larger amounts or over a longer time period than was intended, missing out on personal or occupational or social obligations because of alcohol use. Basically, alcohol use interfering with your daily life, as well as symptoms of tolerance or withdrawal symptoms, which we didn't even get into in detail, but withdrawal symptoms are actually really important because alcohol withdrawal, unlike withdrawal from a lot of other recreational substances, can actually be fatal in and of itself.

In what way? So alcohol withdrawal, because of its effects on the brain, especially with chronic use of alcohol, the effects on the brain, sudden withdrawal can precipitate seizures, which can then lead to death. Okay. So alcohol withdrawal is very, very serious. And we talked a little bit about this a lot earlier on, but in terms of like the overall risks of alcohol use disorder, since you talked so much, Aaron, about how. All humans, for the most part, are able to metabolize alcohol in the same way. Alcohol is affecting our brains in essentially the same way. Hijacking these dopamine pathways, any human has the potential of being susceptible to an

alcohol use disorder, to an addiction associated with alcohol. But we also know that there are variation in things like metabolism. There are genetic components to alcohol use disorder. but again, I don't know of any specific genes that would make one more or less susceptible, per se, that we have a lot of evidence for. Right. And then there are, of course, a lot of environmental risk factors, especially increased stressors that lead to increased risk. So things like a history of abuse of any kind, household instability, other psychiatric disorders, etc. And I think what's really depressing is that alcohol use disorder and its risk actually peaks among young.

adults age 18 to 25. But of course any age group is also susceptible. I think too there, like you said, Aaron, there's so much stigma surrounding alcohol, alcohol use, alcohol use disorder. Not drinking alcohol. Right. It goes on so many different spectrums. And I think it varies so much culture to culture as well as varying so much over time. So I would. So I would, was trying to find, like, data on, like, real data on the perceptions and stigma, but I didn't really find data on it. But I do think that these sort of dichotomous perceptions of, like, is alcohol good? Is alcohol what, you know, rich people drink alcohol or is alcohol for, is it what poor people do? Is it associated with, you know? Is it good for you when you drink red

wine or is it bad for you when you drink beer or whatever? Or vodka or whatever. Right. I think that these sort of dichotomous perceptions really wax and wane over time. So I wish that we could just not stigmatize one way or the other and rather just kind of understand this drug, understand the effects that it's having on our brain and why it's making us feel the way that we feel and understand what it means if we do and vibe versus don't imbibe. I don't know. But that's just me. Yeah. I mean, I think like more nuanced discussion.

And that's what I think is really frustrating about a lot of the headlines that you see, whether it's about, you know, a glass of red wine or coffee or whatever. Like it's sort of, well, here's the sound bite. Here's the one bottom line. And that is that it's going to help you. And that's, it's way more complicated than that. It's so much more complicated than that. As usual. As usual. And it's never. going to be like it's never going to be as simple as right i don't know yeah we always like i feel like the increasingly persistent theme in this season is nuance nuance yeah it's going to be our subtitle next season season four nuance it is though it really is especially when it comes to alcohol you know

right it's like i mean i found this episode challenging to research on a number of levels. One is like the sheer overwhelming, you know, abundance of literature about the subject. But the other is sort of like all of the stuff that I found was very, you know, there was a certain bias to it. Yes. Whether it was pro-alcohol or whether it was anti-alcohol, like there was something, you know, and I really don't want to present my, you know, views as the right views. Right. This is the truth or this is not the truth.

or this is not the truth. Like I wanted to present a variety of things. I wanted to, I don't know. But yeah, I found it challenging to do also in thinking about how I feel about alcohol. Right. Trying not to put our own biases into it. Obviously, we make quarantinis for every one of these episodes. Right.

But we also make placebo-tas for every one of these episodes. And sometimes they're way more delicious than, and way more appetizing. Definitely try the placebo-a for this episode. It's great. It is. No, I know. It's a difficult subject to navigate. I will say in talking a little bit more specifically about alcohol use disorder,

because I think especially when it comes to alcohol use disorder, there is such a heavy stigma with addiction in general. Addiction is so heavily stigmatized. Oh, yeah. So I do want to mention that we have a lot of new therapies to treat alcohol use disorders. disorder. There was a time where we had nothing in terms of pharmacologic treatment and kind of for a while it was like AA is the only thing. And then there was a Cochran review from 2006 that concluded there was no evidence to show that AA, so that's Alcoholics Anonymous or any other treatment modality was more effective or even effective at all. And then another review came out in

2020, which media reports were like, A, A, and other 12-step programs were the only thing that works in there the best. That's how the media reported it. Of course. But there were kind of a lot of methodological flaws in that analysis. And the two studies, the 2006 and 2020 study, they don't really actually use the same outcome measures. And okay, maybe this is me expressing my bias. But I also found a commentary on the most recent Cochrane review that was pointing out that the studies really just measured the total amount of abstinence, like the total days of abstinence as their main outcome measure. And like maybe that's not the best outcome measure that we should be using as treatment success. Because for one, a lot of people might be deterred from ever seeking treatment at the prospect of having

to have lifelong abstinence be the only correct outcome. Right. non-abstinent goals might be a lot more retainable for a lot of people. And also just in general, quality of life and psychological well-being weren't considered as outcomes in these studies. I will post all three of those articles so that people can freely read and choose and judge them for themselves. But we do also now have a number of different pharmacological treatments for alcohol use disorder. We actually have one that's not great. It's called dysulfram, and it basically inhibits aldehyde dehydrogenase. So it's like basically mimicking that form of genetic, yeah,

right, right? It's exactly what it does. So you have to take it if you plan on drinking or you think that you're going to drink, and then if you drink, you will feel terrible and you will barf and you'll be flush and you will feel awful. You'll have all of the. symptoms of, yeah. Exactly. So it's not very effective because if you, you just don't take it if you want to drink. You know what I mean? So it takes a lot of willpower to take that and then know, et cetera. There are other pharmacologic treatments that interact more directly on your brain to basically decrease the dopamine mediated reward effects of alcohol. So you don't get that feel good reward system as much. And it has been shown to reduce alcohol consumption.

Huh. And then there are other ones as well that seem to have evidence to help maintain abstinence in people who have already started to abstain and want to continue to abstain. And then there are still more that are not necessarily in the U.S. FDA approved but are used in other countries or maybe are used off-label. So I think the overall message is that if somebody feels like they might have alcohol use disorder or like they might want to get help with their alcohol use disorder, but they don't know where to look, there is help out there. And I think that's important to know because there's a lot of studies that demonstrate how widespread alcohol use disorder is in the United States and in other countries as well, but how few people ever actually seek help for it. Yeah.

Yeah. That's all I have, Erin. Oh, are we done? Two hours later? Just two short hours. This was, I learned a lot. Yeah, me too. I mean, I always do, but this one was sort of hit a lot of different corners of my brain.

Should we do sources? Yeah, we should. So I read a couple of great papers about sort of the evolutionary origins of alcohol. dehydrogenase. One I already mentioned Janiac at all from 2020, and there's another one from Kerrigan at all 2014. And I also read a couple of books. One is by Rod Phillips, and it's just called Alcohol, a History. It's very thorough. And the other one is by Edward Slingerland, and it is called Drunk. And so this is the one that talks a lot about why humans drink and why do we keep drinking? So I will say I have mixed feelings about it simply because I don't know

if there necessarily has to be a reason, like an evolutionary reason for all the things that we do or choose to do. It just, anyway. But I talked a lot about that in the history section. So anyway, Aaron. I have a large number of papers for this episode. A whole bunch of things. A whole bunch of that go into way more detail than I did on the pharmacokinetics of alcohol metabolism, as well as the chronic effects of alcohol, etc. I will post all three of those, the two Cochrane reviews, and the response commentary to the Cochran Review about Alcoholics Anonymous and other 12-step programs, and a whole host more, including that really great paper of a list of common

hangover cures throughout history. Yeah, I can't wait to read that. It's really good. You can find all of our sources from this episode and every one of our episodes on our website. This podcast will kill you.com. Thank you to Bloodmobile for providing the music for this episode and all of our episodes. Thank you to the exactly right network of whom we are so proud to be a part. And thank you to you, listeners.

You made it not only through this long episode, but also this long season. Yeah, and like three seasons before it too. Yeah, and hopefully you'll wait for us on the other side for season five. Thank you also to patrons who support us on Patreon. We cannot express enough how much it means to us. Thank you from the bottom of our hearts. And in the meantime, you know, make sure that you're subscribed to all of our social media channels and to our podcast on whatever podcast app you use.

that when season five drops, you'll get a heads up. If you need more podcasts in your ears in the meantime, Exactly Right has a whole host of so many shows that you can choose from. So definitely check out the other Exactly Right shows as well. Exactly right. Well, until next season. Yeah. Wash your hands. You filthy animals.

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