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Why Does Alcohol Affect People So Differently? · So That's Why

• 0:05
  Jen: Welcome to the So That's Why podcast, where we unpack the
• 0:08
  science behind everyday questions.
• 0:10
  I'm Jen.
• 0:11
  Chris: I'm Chris.
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  Matt: And I'm Matt.
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  Jen: Okay, so here's one that can sometimes be slightly awkward, but
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  is actually genuinely fascinating.
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  Why does alcohol affect people so differently?
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  'Cause in any group you'll see that one person getting visibly merry
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  after two drinks, while someone else can go through the whole evening
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  looking completely unaffected.
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  Matt: Yep, we've all seen it, that social dynamic that has a different person
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  responding to alcohol in a different way.
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  Uh, one who's chatty after half a glass, and then there's one who's treating their
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  first bottle of wine like it's a warm-up.
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  And neither of them can really explain why that sort of phenomenon exists.
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  And I possibly would, would, uh, posit to you that they might not even care.
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  Chris: Or remember the next day.
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  Yeah,
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  Jen: yeah, yeah.
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  Or either.
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  Yeah.
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  Chris: Um, and the answer here actually turns out to be one of the most
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  individual pieces of biology there is.
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  So it's shaped by, uh, genetics, by body water content, by sex, age, what
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  you've eaten, medications, even how you're feeling before that first drink.
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  Jen: So by the end of this episode, you'll understand why the same few drinks
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  can land completely differently on two people sitting side by side, and we'll
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  also look at how drinking patterns are changing and what the science actually
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  says about lower risk approaches.
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  Matt: Yeah, and just to say upfront, we're not here to tell
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  anyone what to do with alcohol.
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  It's more about understanding why responses differ so
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  much in the first place.
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  Chris: Yeah, exactly.
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  So the science we're looking at is the same for everyone, it's just
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  with different starting points.
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  And just to also say, we're only covering the science today.
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  We're not discussing that one friend that you always have who seems to go missing
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  every time it's their turn to buy a round.
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  Jen: Yeah.
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  Matt: I wonder if there is actually science for that.
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  Jen: Yeah.
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  Or if you are that friend, buy a round.
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  Chris: Sha- Shauli looked at me when you said
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  that.
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  Jen: Okay, so let's start with, um, giving this a number to
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  give it, like, a sense of scale.
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  So researchers have identified over 400 genomic regions and more than 500
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  genetic variants linked to how people experience and metabolize alcohol.
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  Matt: Which again, just wanna meet the person that counts these, right?
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  So there's over 500 genetic factors influencing how you respond before
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  you've even had a sip, uh, of the drink.
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  Uh, which is a lot of va- variation, I think, baked in right from the start.
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  Chris: Yeah, it really is, and that's why kinda blanket advice doesn't really
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  fit well when it comes to alcohol.
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  So two people can have the same drink, or drink the same amount at the same pace,
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  but still end up with very different blood alcohol levels and, of course, effects.
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  Jen: Which makes the idea of, "I know my limits" only part- True, because
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  those limits, they shift depending on sleep, food, stress, age, and
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  like we said before, medications
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  Matt: Yeah.
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  So the same person, uh, on a Tuesday after dinner has a very different sort of
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  physiological setup, uh, from that exact same person- Mm … on a Friday night
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  after a long week and possibly no food.
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  Jen: Mm.
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  Chris: Yeah, and this whole thing comes down to how the liver
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  processes the alcohol that we drink.
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  So alcohol, or ethanol, it gets absorbed through the stomach and the
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  small intestine into the bloodstream.
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  Then the liver breaks it down in, in two main steps.
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  Jen: Okay, so step one, it uses an enzyme called alcohol dehydrogenase,
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  or ADH, and that converts the alcohol into acetaldehyde.
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  And acetaldehyde is the nasty part, so it's toxic and carcinogenic,
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  and it's responsible for a lot of the unpleasant effects of drinking.
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  Matt: Yeah, like the headaches and the nausea.
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  They don't really come from the alcohol itself.
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  It's what the body, um, turns it into, isn't it, while processing it?
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  Chris: Mm. Yeah, that's right.
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  And step two uses another enzyme called aldehyde dehydrogenase.
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  So this is ALDH, and this is to convert the, the acetaldehyde into
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  acetate, which is then broken down into water and carbon dioxide.
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  Sorry, I know we're using a lot of, uh, chemically rich names here, and I'm not
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  quite pronouncing some of them correctly.
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  But, uh, there you go.
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  Matt: Yeah, I'm just
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  glad I'm not supposed to say any of them.
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  That's-
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  Jen: But the key, um, point in this process is speed.
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  So the liver can only process alcohol at roughly one standard drink per hour.
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  So anything faster than that, it just builds up in your system.
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  Matt: Yeah.
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  So it's not that the liver is struggling per se.
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  It's, you gotta think of it more like a single, uh, road, a single lane road
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  with traffic sort of building up behind
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  it.
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  Jen: Mm-hmm.
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  Yeah.
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  Chris: Yeah, pretty much.
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  It is like that.
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  And, um, that speed is largely genetically determined, uh, because
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  those enzymes vary between people.
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  Jen: So the two main ones are ADH1B, and that enzyme controls how quickly
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  alcohol becomes acetaldehyde, and then ALDH2, and that controls how quickly
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  the acetaldehyde then gets cleared.
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  Matt: Can I just say well done, guys, on the, uh, on the naming
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  conventions going on here.
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  Chris: Yeah.
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  Jen did better than me on that one.
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  One, one-nil.
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  One-zero.
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  Jen: Woo.
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  Matt: Jen's degree in biochemistry.
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  Jen: It's finally coming into
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  play.
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  Matt: Yeah.
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  Well done.
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  So if one, uh, runs fast and one, one of these processes runs fast
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  and one runs slow, you're gonna get this backlog, aren't you?
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  You're gonna get, um, a buildup.
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  Uh, and that's the toxic bit, isn't it, in the middle?
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  Mm-hmm.
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  Which sounds, if I'm honest, a little bit unpleasant.
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  Chris: Yeah, it certainly can be.
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  And, um, it's especially well-studied in East Asian populations.
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  And around a third carry a variant of this ALDH2 that doesn't work properly, which
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  causes flushing even after small amounts.
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  Jen: And then there's been, there's been lots of other genetic studies that have
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  confirmed that both of these enzymes, they strongly influence that response.
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  So it's not psychological, it's the body genuinely struggling to
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  clear the acetaldehyde efficiently.
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  Matt: And I guess that would naturally discourage, in theory, heavier drinking
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  for, uh, a lot of people perhaps.
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  Jen: Mm.
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  Chris: Yeah, that's one of the leading theories.
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  Um, the physical reaction acts as a pretty good built-in deterrent, doesn't it?
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  Uh, but where people do drink through it, just through kind of stubbornness
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  or desire- … um, the acetaldehyde exposure carries increased long-term risk,
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  like particularly with certain cancers.
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  Jen: So genetics is the foundation, isn't it?
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  Then everything else layers on top.
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  Um, I think what, biological sex, that's one of the most consistent
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  differences, and also a lot of it comes down to body water.
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  Matt: Yeah, so when people say men and women can't really be
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  compared drink for drink, unless they're talking about my mum-
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  there's actually a sort of physiological reason, reason behind that, right?
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  Jen: Shout out to Matt's mum.
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  Matt: Yeah, yeah.
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  Legend.
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  Chris: Yeah, there is.
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  I can't comment about your mum.
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  And I, I've not had a drink with her, but it sounds like it'd be good fun.
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  Um, but alcohol is water soluble, so it distributes through, um, evenly
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  through the body in, in its water.
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  And on average, men have more total body water.
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  So the same drink in men is of course more diluted than in women.
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  Matt: Mm.
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  Jen: And here's another interesting difference.
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  So men have ADH activity, so the enzyme, in their stomach lining, so they can
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  metabolize part of the alcohol before it even reaches the bloodstream.
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  And guess what?
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  Women don't have that same level of enzyme, so they can't, um, metabolize it.
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  So for men then, the same glass of wine doesn't enter the system in quite the same
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  way from the start as it does for women.
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  Mm.
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  Chris: Um, yeah, precisely.
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  And if you combine that with body water differences and you get a
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  higher blood alcohol concentration from the same intake in women.
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  Jen: So body composition matters too then, doesn't it?
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  So muscle holds more water than fat tissue, so higher muscle mass
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  generally means lower blood alcohol concentration for the same drinks.
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  Matt: So two people of the same weight can still have very
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  different responses depending on their actual bodily composition.
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  So the scales themselves don't really tell the full story.
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  Jen: Mm.
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  Chris: Yeah, it's true.
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  And then we come to age, and age adds another layer.
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  So we lose roughly 3 to 8% of lean muscle mass per decade after 30.
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  That's not great, is it?
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  I'm not, always be these bad stats are good for that.
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  Um, I'm sure there are benefits of getting older but, you know.
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  We, we, we bring the facts.
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  Losing lean muscle mass is one of them, yeah.
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  Um, and of course, if you lose lean muscle mass, your kinda total body
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  water is gonna decrease over time too
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  Jen: Well, I'm joining your joy-bringing party.
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  The, uh, liver also becomes less efficient, so alcohol
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  stays in the system longer.
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  And that's why people often say, don't they, that drinks hit harder
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  in their 40s than their 20s?
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  It's a real physiological shift.
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  Matt: Yeah.
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  And it also explains why people naturally start moderating as they get older.
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  Their body actually starts to give some immediate feedback.
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  Jen: Mm.
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  Chris: Yeah.
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  And another consideration with age is that, um, around 80% of adults over
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  65 are taking at least one medication that can interact with alcohol.
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  So the situation does become more complex with age anyway.
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  There's more kind of factors going on.
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  Jen: Yeah.
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  And then there's what's happening in the moment, isn't it?
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  Like food, drink type, and context.
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  They all matter.
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  Matt: Yeah.
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  And there's this idea that I've heard, you know, that you're lining
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  your stomach before drinking.
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  My question is, does that actually work?
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  Chris: It does, and, uh, it works because food slows gastric emptying, which I
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  appreciate sounds pretty disgusting.
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  Jen: Very
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  scientific there, Chris.
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  Chris: Yeah.
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  Sorry about that.
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  That's put me off my lunch now.
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  Um, but especially meals that have got, um, fats and carbs.
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  They reduce how quickly that alcohol is absorbed, so it can significantly
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  reduce peak alcohol blood levels by eating the right kind of food.
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  Jen: And drink type matters, too.
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  So spirits absorb faster, while beer and wine are slower.
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  And then carbonation speeds up absorption, so, like, sparkling drinks, they often
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  hit faster than people would expect.
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  Matt: That's an interesting one, isn't it?
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  So your prosecco at a wedding on an empty stomach is basically
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  the perfect storm of chemistry.
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  Jen: Or a way to get people to buy more at the bar, maybe.
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  Matt: Yeah.
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  You put… But e- I'm not saying either way.
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  Chris: So if you have a prosecco on an empty stomach at a wedding
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  reception, you can say, "This is just a chemistry experiment gone wrong."
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  Jen: Absolutely.
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  Chris: Who knows?
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  Jen: And here's another one, though, that's worth us clearing up.
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  Um, water doesn't lower blood alcohol levels or speed up metabolism.
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  It can help with hydration and headaches, but not the intoxication itself.
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  Chris: Yep, it's true, and studies have shown that, um, water only
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  has a modest effect on hangovers.
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  Uh, so the main drivers of inflammation and oxidative stress aren't
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  really fixed by hydration alone.
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  Matt: So, you know, the big sort of glass of water fixes everything
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  strategy is mostly for comfort.
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  It's not chemistry.
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  Jen: It's always a good idea, though, isn't it?
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  Chris: That's right.
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  I mean, hydration, as we've covered a lot, helps, kind of, everything.
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  It's the root to- goodness across the board.
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  Um, and it, course it will make you feel a little bit better, but it doesn't really
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  address what's going on biologically.
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  And, uh, that's where medications become another huge factor here.
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  So as I mentioned earlier, a lot of adults are taking medication, particularly
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  as they get older, and I think it's around 40% of adults across all ages
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  are taking something, some form of medication that can interact with alcohol.
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  And these interactions show up a significant proportion of emergency
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  admissions related to alcohol.
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  Jen: Mm.
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  Matt: That includes pretty common things too, doesn't it?
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  Like we've got painkillers, we've got antihistamines, sleep
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  aids, they're all involved.
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  Chris: Yeah, all of those.
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  And some amplify sedation, others affect, uh, liver metabolism, some
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  increase bleeding risk, and all of these effects can happen at actually
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  relatively low alcohol levels.
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  Jen: And that ties into how people think about tolerance.
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  So when someone says they hold their drink well, that's usually functional
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  tolerance, the brain adapting, so the outward signs are reduced.
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  Matt: Yeah, but that doesn't mean the internal effects are reduced.
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  Chris: No.
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  So the, the brain compensates behaviorally, but the liver
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  and other organs are still processing that alcohol load.
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  Jen: And over time, um, reverse tolerance can happen in heavy drinkers too.
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  So where liver damage reduces metabolism, so small amounts
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  suddenly have a stronger effect.
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  Matt: Yeah, so the system can actually swing the other way entirely.
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  Jen: Mm.
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  Chris: Yep, it can.
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  And of course, um, mood and stress also matter a great deal here.
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  So anxiety, uh, fatigue, low food intake, they all reduce your body's
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  resilience to the effects of alcohol.
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  Jen: And those kinds of factors are, they're partly why drinking
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  patterns are shifting more broadly.
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  So it's worth us, um, noting that behavior is changing.
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  So in the UK, around a third of 18 to 24-year-olds don't drink at all.
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  That's quite big.
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  Matt: It's a real shift, eh?
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  Compared to certainly, I would say my generation.
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  Mm. You know, previous generations.
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  And there's also this sort of drink less, drink better trend, which seems
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  to be happening more broadly as well.
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  Jen: Mm.
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  Chris: It is, and so many young people seem to just go out at
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  midnight and, and dance rather than frequent the pubs, isn't it?
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  Mm. Yeah.
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  Which is not good for the pubs.
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  You gotta keep the pubs going.
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  Or be a thing of the past before too long.
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  Do you get pubs in the US?
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  Sorry, US customers, bars.
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  Yeah.
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  Matt: Yeah, yeah.
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  Yeah.
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  There we go.
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  Yeah, yeah.
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  Chris: Um,
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  Matt: there was a- We should do for pubs what Clarkson did for farming.
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  Oh, no, wait, he's doing pubs as well now, isn't he?
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  Jen: Yeah, he is.
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  Matt: Okay, carry on, Chris.
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  Sorry.
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  Chris: Can you explain Clarkson for our listeners?
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  Matt: Oh, they all know who Clarkson is.
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  Clarkson's a worldwide phenomenon.
• 14:05
  Oh,
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  Chris: is
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  Matt: he?
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  Is he?
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  Yeah, yeah.
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  Mm. Clarkson Farms.
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  Chris: Is, is he our best export?
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  Matt: I… Best is probably a l- Yeah.
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  I don't know.
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  Chris: Yeah.
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  Anyway.
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  Sorry, I took us completely off on a tangent.
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  Yeah, yeah.
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  But I'll try and bring it back.
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  So back to Gen Z, there was a 2024 study, and it found that most Gen
• 14:21
  Z consumers, they've reduced this alcohol intake in the past six months.
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  But there is a bit, bit of a change.
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  So some more recent data has shown some slight re-engagement with alcohol
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  w- among the Gen Z. Mm. So it's not kind of straight line, that's it.
• 14:35
  Uh, there is a bit of a shifting pattern.
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  But the overall trend is this- Mm … reduced alcohol intake.
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  Mm. Which is probably not a bad thing.
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  Jen: No.
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  But, and across all age groups, I think moderation is increasing,
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  even if the reasons why differ.
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  Chris: So the UK guidance recommends no more than 14 units of alcohol
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  per week spread across several days, and you've also got to
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  include regular alcohol-free days.
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  Jen: So to put that into context, that's roughly like six pints or six
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  medium glasses of wine across the week.
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  And importantly, there is no completely risk-free level.
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  It's not.
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  It's about reducing risk, isn't it?
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  Not eliminating- Mm … it entirely.
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  Matt: Yeah.
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  So the pattern that seems to emerge is pacing, spreading intake, sort
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  of eating properly, and being aware of personal factors like
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  medication and mood, for example.
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  Chris: That's a fair summary, and I think you've definitely taken
• 15:29
  my captain sensible hat today-
• 15:30
  Matt: I have
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  … Chris: which is good.
• 15:31
  Matt: I, I don't know what's going on, Chris
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  … Chris: I'll pass the baton.
• 15:33
  Jen: Do you like, do you like this role?
• 15:34
  Yeah.
• 15:34
  Matt: No.
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  You can have it back for the next one.
• 15:38
  Jen: Okay.
• 15:39
  So why does alcohol affect people differently?
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  Chris: It's because it passes through a system that varies
• 15:45
  massively between individuals.
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  So genetics set enzyme speed, uh, body composition sets distribution, age
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  shifts metabolism, and food, drink type, medications, and mood, they all modify the
• 16:00
  response we have to alcohol in real time.
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  Jen: Which means the same drinks can land completely differently depending
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  on the person, not because anyone is doing anything wrong, but because
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  everyone's biology is different.
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  Matt: Yeah, and it's less about willpower and less about tolerance,
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  um, but more about individual chemistry doing really what it's built to do.
• 16:22
  Chris: Yep.
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  And once you understand that, a lot of the kind of variation we see
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  between people, uh, like that you see socially starts to make more sense.
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  Mm.
• 16:29
  Matt: So next time you're out, you're basically watching, uh,
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  multiple different biological systems sort of reacting in real time.
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  One big human experiment- … which is actually slightly humbling.
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  Jen: It is.
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  And it's a good reminder that normal is a wide range when it comes to biology.
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  So that's why alcohol affects people differently.
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  That's it for this week.
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  Hit subscribe and let us know what we should explore next.
• 16:58
  Thanks so much for geeking out with us.
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  But for now, that's it from me.
• 17:02
  Matt: That's it from me.
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  Chris: And that's it from me.
• 17:05
  Jen: Bye for now