Among the blossoms, waits a jug of wine. I pour myself a drink. No loved one near 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 Lee Bi, also known as Lee Poe, who was, according to this source, one of the greatest poets of China's Tang dynasty, or of all of history.
Perhaps.
Lee Bi was a martial artist, an academic genius, and also a lover of wine and a member of the group Six Eyed 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 eighth century.
The eighth 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 Ollman Updike, and this is this podcast will kill you.
It is and it's a 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 finales. This is a big one.
Can you can you picture us four years to go when we were doing our first season in my back bedroom in my in our tiny house, Like can you could you ever have imagined that we would be here doing this now?
Eric, You know what, I don't know if I like dared to hope that we would still be doing it.
Yeah, 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 it's true. Yeah, so after this episode, don't worry, we will be coming back. So it's 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.
You're highly looking forward to it.
Yeah, just a little bit of time to rest our brains and to get some other stuff done that in the background. And you know, if you're looking for more of tpwk hy to like fill that need while you're gone, you should definitely check out our reading lists, our bookshop dot Org affiliate account, our Goodreads list, which, by the way, I've I'm not allowed to add any more books. I've capped it at one hundred, Like I've added one hundred 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 that 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'd 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 quarantiney exactly. So what are we drinking this week?
We're drinking poor choices? Get it like po you are. 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 I'm not exaggerating.
Tell us what's in it? Aarin?
So you start with mead, and we chose mead because meat is one of the oldest alcoholic beverages also known as honeywine. And then we kind of did a little fun sidestep. We're doing a shrub and 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,
filtered out and it's absolutely delicious. I made a shrub for this of honeycrisp apples and honey apple cide or vinegar, the zest of a lemon, all spice annis 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 placy Brita. And don't worry, we'll post the full recipe for that quarantine and the non alcoholic Plasy Brita on our website, this podcast with kill you dot 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 dot 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.
So alcohol, by which I mean Aaron ethanol? That's what you mean? Okay? Good?
Yeah, by the way, I think we're going to be using these interchangeably throughout Okay.
Well 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 b 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 Arin.
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 effects 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 Aaron, I want to hear from you about how long.
We've been giving ourselves heny over.
And then at the end we'll wrap it up with like this 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 quarantinie, 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 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 Aaron is what 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 kidnies. 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 gabba 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 GABBA. 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 GABA receptors in a slightly different way. But there are lots of other sedata drugs that act on different.
Receptors because different pathways. Okay, yeah, yeah, I have a question about diuretics. Okay, oh God, 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 love it.
Okay, okay, we You know what we can do.
Is do an episode about heart failure and then we can talk a lot about diuretics.
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 our brain, which are our brain's innate reward system. 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 nod
or vomiting. Our motor and our sensory systems can start to become impaired 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, et cetera, et cetera.
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 special 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 point zero eight percent is like
the legal limit in the US. At concentrations below point zero eight percent, in general, you're not having as much of the motor and cognitive deficits at concentrations above that, especially approaching point one percent. That's when you have like sedation impaired motor and sensory Once you get to like point three to point four or above, especially above point five percent, 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. 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 metabolized 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 a 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 the absorption exactly.
Okay, Yeah, interesting.
Yeah, eating does help, And as we can continue talking about, it's 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 toxic intermediate. 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 ninety percent 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 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 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 same 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 flashbacks to sell bio and it's kind of given me the hebgen.
I'm sorry, I'm trying to avoid saying like the TWCA cycle. Okay, 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 cofactors 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.
HM. 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.
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, the night before you're the same as with cofactors.
That's exactly what it is. You're using up your bodies 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, 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, trembling.
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 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 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 bodies 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. 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 creddy with a hangover.
It makes sense.
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 Wernicky Corsicov syndrome.
Have you heard of this?
Aarin, No, I don't think so.
So Wernicky Corsicov It's actually it's two different syndromes that are kind of lumped together as one. It's Wernickey's encephalopathy, which is an acute and potentially fixable disorder, as well as a longer term, irreversible dementia that's known as Corsicov syndrome. Both of these are actually caused not by alcohol directly, but by a thiamine or a vitamin B one DIFFI. So this is a syndrome that can occur with no
alcohol whatsoever. But today, because we like fourti fy flower and things like that, over ninety percent 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.
Gotta 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 care, affects our overall electrolyte balance, including magnesium, which is an important electrolyte and an essential cofactor in thiamine utilization.
It really is all about the cofactors.
It really is all about the cofactors.
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 ada the alcohol dehydrogenase gets completely saturated with ethanol, even at really low concentrations, so it's working at its max
from day one. 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 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 a 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 build up not of alcohol, but of acid aldehyde, the toxic intermediate.
Yeah, and so 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 gonna talk a little bit more about it in the history of section.
Oh good, I can't wait. Yeah.
So do you have any questions, Arin, 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 questions. 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 that 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, 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 the thing that's important to point out is that while we have 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, et cetera.
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 twenty seventeen that suggested, like and it got a lot of press at the time, that like, oh, less than thirty two grams a week, which is two alcoholic drinks. Those 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 US 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.
And 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 dated I don't think in general, it's something that is recommended as a thing to keep you healthy by any means, right, right, Yeah, that makes sense.
But so that's pretty much the biology of alcohol. Aaron's a lot.
I have one more question, and it has to do with hangovers. Okay, and so if we know what causes hangovers, like, how do you replenish cofactors besides just time?
Time eron? Yeah, did you read the paper?
I found a paper that was just eighteen pages of hangover cures.
No, oh, my gosh, I have nothing about hangovers in my history sections.
Okay, well, I will post a paper that's like eighteen or more pages of just old timey hangover cures.
It's a mold gosh, you would love it.
Oh, I didn't see that.
Yeah, none of them are real to actually treat a hangover, A 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 your 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 aceta menifin.
Right, So, Aceta menifin is thailenol, 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, 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. Okay, the history of alcohol.
Yes, all of it.
It's 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. I know.
It's really 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 or so, because yeah, anyway, 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 possess this 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 for enzyme, and this this mutated form allows
us to metabolize alcohol much more efficiently than most other animals, like forty 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 mutation at the same spot in that gene four eighth four 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 Iis and koalas.
What there'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, the large fruit bat Iies koalas, they have like different gastrointestinal systems compared to like grade apes, right, and so whether the function of that mutated alcohol dehydrogenase is the same in those as it is in these you know, grade 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 ten 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.
And some of this fruit would have contained ethanol concentrations as high as like eight point one percent. Wow, 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 neighbors. 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, Iies et. Cetera. 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 efficient, and why some animals have actually lost
the ability altogether. So there's a recent study from twenty twenty by janiac at All that showed that the gene for eighty h four for this alcohol dehydrogenase four enzyme, is non functional in some animal species, meaning that it was once there and it once worked, 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 relaxed selection and boom, some of them just 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 metabolized 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 foods.
Fermentation can actually increase the nutritional value of things, make it like more bioavailable 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, 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 piles of fermenting fruit on the forest floor.
But then once humans began to actually intentionally produce alcohol, some more of the downsides began to appear, 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
soak grains produced a fermented alcoholic beverage. 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 one, 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 agricultural revolution.
Huh.
So people started to settle because of the large gatherings rather than able to settle because of agriculture.
They started to 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 our chaeological evidence, such as what we see as go Beckley Tepe, a super old, like eleven thousand 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 the 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 then the other, Like, 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?
Uh huh?
So do you do both? You do both?
Waste not want not wait 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. And to underline that, here are some examples. Yes, there's a twenty thousand year old carving from south west 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 twelve thousand 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 seven thousand BCE, and it was made from like wild grapes, hawthorn fruit, rice, and honey. Grapes were domesticated in what is now Georgia from around seven thousand to six thousand BCE. In what is now Iran, there is evidence of grape wines in ceramics from fifty five hundred to five thousand BCE.
In Armenia, there's an ancient cave 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 thirty four hundred.
BCE, fascinating Aaron.
The oldest preserved liquid alcohol was found in China and dates back to nineteen hundred BCE, and there are references to alcohol in our oldest surviving literary document, the Epic of Gilgamesh from eighteen hundred BCE, and in our oldest law document, Hammerabi's Code from seventeen seventy BCE, which regulated the strength and price of beer and forbade women from drinking it.
Oh oh, okay, a lot of woes on that.
Yeah.
Also, we're going like way back further than the Ebers Papyrus. Is that what you're telling me here?
Oh?
Oh yeah, I mean I'm sure that it's in the Ebers Papyrus. Shame on me for not finding it explicitly.
Wow mm hmm.
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 make really good alcohol from day one.
That's so interesting.
Really, 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 used. And I'll definitely go into some more of these or at least like, you know, a list of examples the things that people used 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 and 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 celebration, you know, Dionysus, Jesus. There were many gods or religious figures associated with like certain alcoholic beverages, wine in particular. But the availability of alcohol in large quantities also revealed, of course, its 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 alls. It was very like, you know what, 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 all 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.
Huh.
The most famous is probably of course the prohibition of alcohol in Islam, which began in the seventh 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 and 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 it cracks me up because I'm like that is still unlike every stadium, every concert hall, every whatever.
You can't bring your own Oh my goodness.
Yep, yeah, I wonder if they I wonder if they sold it for like you know, of course they sold it fifteen dollars for like three ounces of wine.
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 Aarin, 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 seven thousand to ten thousand 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 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 by 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 and 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.
Everything we talk about in this podcast.
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 reliveives is necessary. The author of this book suggests that alcohol and 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 reproduced, just beyond the fact that we like the way we feel when we drink it. Yeah. Maybe, as my younger sister
would say, it's not that deep. Maybe the reason humans drink alcohol is just because we like it, right, 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 ch logical 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 in 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 to pie 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 three thousand 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 Iran, 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 two
thousand 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 simultaneously 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 one thousand BCE, there's a list of five hundred
and thirteen vineyards owned by temples, mostly in the Nile Delta. Wow. Yeah, 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 drink 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 could 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 German 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 four hundred to three hundred 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 amphoras, and I mean enormous. So there's one shipwreck I read about that contains ten thousand amphoras, which is about three
hundred thousand leaders of wine. Ooh yeah, or about four hundred thousand modern wine bottles.
Whoa, uh huh.
Yeah. And ancient Greece also held symposia where wine was consumed in moderation with strict rules. The word symposium actually means fellow drinker or drinking together. I 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. And boy does this echo throughout history.
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 is 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 fourteen hundreds, 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 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 eleven eight nine, was like really old, yeah, 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 misogynistic exclusion, which is pretty easily seen in the depictions from this time showing women brewers as dishonest and unhygienic, and women who drank in
taverns as immoral. Of course, I mean, and this whole thing gets repeated again in Europe in the fifteen hundreds 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 toward its 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 like specialized 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 thirteenth century in China and the sixteenth through the eighteenth 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. 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 seven hundred people from England to Massachusetts in sixteen thirty, there were ten thousand gallons of wine, forty two tons of beer, fourteen tons of water, and twelve 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 two to four percent or six to twelve percent, respectively. Like, it's actually much more alcoholic nowadays, Like your standard beer or wine is more
alcoholic than they used to be. But distilled spirits, like they can be incredibly alcoholic, right, I mean, I would say the range was typically twenty percent to one hundred percent, like just pure ethanol. 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 and 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 practiced 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 were 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 twenty eight years before the nineteen twenty legislation that led to the US wide alcohol prohibition,
and this specific prohibition wasn't repealed until nineteen fifty three, which is twenty 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, 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 US. 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
bands or restrictions more effective than others. And I'm going to focus primarily on the trend towards prohibition that began in the late seventeen hundreds early eighteen hundreds, and then like you know, culminated in the early twentieth century in places like the US, 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 seventeen hundreds, 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 seventeen hundred and seventeen fifty.
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 seventeen hundred to seventeen fifty 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, right 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 dictions around drinking and moral panic about alcohol consumption by women sort of like fed into each other, especially as industrialization meant denser populations and 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 eighteen hundreds, for example, in Paris, although this trend is repeated in many other places, per capita consumption of pure alcohol from spirits rose from two point nine leaders in the early eight eighteen hundreds to five point one leaders in the eighteen forties to nine point one leaders in the late eighteen hundreds. So that's like if you just take what they were drinking
and then calculated the pure alcohol concentration of it. With the introduction of distilled spirits, there was a lot of like, Okay, this is scary, there's 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 eighteen hundreds with a push to replace alcohol with like tea or coffee or hot chocolate or water, and then starting in like the early nineteen hundreds, it turned into just prohibition no alcohol period. Eugenesis took up the cause kind of by listing alcoholism, which was first used as a term in eighteen forty nine by Swedish physician Magnus Huss.
They listed alcoholism as an undesirable trait that shouldn't be passed on to deep spring. It's always I mean, yeah, I know, always, 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 One. 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 very valid statement.
So interesting.
Alcohol was viewed also during this time as weakening the soldiers and the morale of those at home. By nineteen sixteen,
forty five US 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, And on January first, nineteen twenty, the Eighteenth 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 can burns five and a half hour documentary on prohibition in the US, 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, 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 speakeasies 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 m H. And thirteen years later it was repealed by Franklin Elean R. 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 US citizens.
Most countries that attempted some form of prohibition or other did so in a fairly short window of time from around nineteen fourteen to nineteen thirty three, 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 oversight might be
more helpful than anything. I don't know. It feels ridiculous that I am going to try to sum up the rest of the twentieth century and alcohol in like two sentences. But that's just how big the history is. Since prohibition, our relationship with alcohol and our understanding of it has
changed like quite a bit. Yes, our good old friend to Louis Pasture discovered the process of fermentation in the mid eighteen hundreds, which kicked off germ theory, but it wasn't until the nineteen forties 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 nineteen thirty five, 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, and I'm sure that the current status is also complicated.
Yeah.
So, Aaron, what's happening with alcohol today?
Let's 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, Arin, Okay, Okay.
So, looking first at the US, in a paper from twenty nineteen, I found that between two thousand and six and twenty ten, 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 orrhosis or more chronic causes of alcohol associated death, et cetera.
Just any kind of alcohol associated death in the US was about eighty eight thousand a year, which represents almost ten percent of all deaths.
In the United States. Wow. Yeah, that's a lot higher than I realized.
Yeah, in twenty ten, and remember that in the US have to be taken with a grain of salt, but the estimated alcohol related costs in the United States were almost two hundred and fifty billion dollars, seventy seven percent of which were attributable to binge drinking.
Okay, so yeah, we didn't really talk about binge drinking.
Yeah, but that, yeah, we didn't. Bine drinking is very bad if we take a broader perspective and look worldwide. Worldwide, according to the World Health Organization, about three million deaths every year result from harmful use of alcohol, which worldwide represents five point three percent of all deaths. Wow, and overall about five point one percent 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 two thousand and four from the World Health Organization, because that data that I just said is from twenty eighteen, but at two thousand and four paper estimated that one point five percent of global deaths were attributable to alcohol, and three point five percent 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, but interesting, it is interesting. So you mentioned at the end of
your history section EIR and alcohol use disorder. So the DSM five, which I think that we've talked about on this podcast before.
Right, I think so think a long time ago, A long time ago.
The DSM five 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 an 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 symptom 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 erin 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 and 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. 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 eighteen to twenty five. But of course
any age group is also susceptible. I think to their, like you said, Aaron, there's so much stigma surrounding alcohol, alcohol use, alcohol use disorder, and.
Drinking alcohol 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 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 im vibe.
I don't know, 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 exactly, 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 months.
Yeah we are so title next.
Season four nuance.
It is, though, it really is, especially when it comes to alcohol, you know, m.
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, 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 quarantine for every one of these episodes.
Right, but we also make plasy beritas every one of these every one of these episodes, and sometimes they're way more delicious then and way more appetizing.
Definitely try the plasi berita 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. So I do want to mention that we have a lot of new therapies to treat alcohol use 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 Cochrane review from two thousand and six 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 twenty twenty which media reports were like AA and other twelve 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 two thousand and six and twenty twenty 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 abstinate goals might be a lot more.
Attainable 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 disulfram and it basically inhibits aldehyde dehydrogenase.
Oh so it's like it's like that basically mimicking that.
That genetic Yeah, right, that'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 flesh and you will feel awful.
You'll have all of the symptoms of exactly.
So it's not very effective because if 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 etc. 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 US 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 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, that's all I.
Have here in Oh, are we done? Two hours later? Just two short hours, this was I learned a lot. Yeah, 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 jenik at All from twenty twenty, and there's another one from Carrigan at All twenty fourteen. 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 that go into way more detail than I did on the pharmacokinetics of alcohol metabolism as well as the chronic effects of alcohol, et cetera. I will post all three of those, the two Cochran reviews and the response commentary to the Cochran review about Alcoholics, Anonymous and other twelve step programs, and a whole host more, including that really great paper of a list of common hangover cures throughout.
History, and you can't glad 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 dot com.
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Yeah, and like three seasons before it too.
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You feel the animals
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