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Jen: Welcome to the So That's
Why podcast, where we unpack the

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science behind everyday questions.

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I'm Jen.

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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.

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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

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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.

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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

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my captain sensible hat today-

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Matt: I have

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…
Chris: which is good.

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Matt: I, I don't know
what's going on, Chris

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… 
Chris: I'll pass the baton.

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Jen: Do you like, do you like this role?

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Yeah.

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Matt: No.

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You can have it back for the next one.

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Jen: Okay.

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So why does alcohol
affect people differently?

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Chris: It's because it passes
through a system that varies

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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

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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.

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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.

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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.

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Thanks so much for geeking out with us.

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But for now, that's it from me.

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Matt: That's it from me.

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Chris: And that's it from me.

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Jen: Bye for now