we all know too much alcohol is unhealthy but what about moderate drinking, like one or two
glasses a day? the idea that moderate drinking can have health benefits, particularly for the heart,
goes back decades. after all, red wine contains antioxidants like polyphenols
and wine is a feature of the mediterranean diet so it all seems to come together. and science appears
to back it up, people who drink moderately tend to have less cardiovascular disease
less than those who drink a lot, that's not surprising, but get this, also less than those
who don't drink at all. that's what's known as a u-curve, sometimes also called a j-curve
because it kind of looks like those letters. okay but this is observational evidence aka
epidemiology, we just ask people how much they normally drink and then try to relate that to
health, and as we've discussed in previous videos we want to be cautious with this type of evidence
it's important data but we can't assume that it's cause and effect. it could be a real effect
of the moderate drinking or it could just be a coincidence. maybe moderate drinkers also
exercise more and eat better in general. so are the heart benefits of moderate drinking the real deal
or just a myth? how can we even tell? well, the gold standard is a randomized clinical trial
split volunteers randomly and put them on different amounts of alcohol for a while
ideally years, and see what happens. that's really hard to do, it's really expensive and there
are ethical issues. there actually was a large trial in the works looking at moderate drinking
but they ended up pulling the plug over concerns with its design. a team in australia did complete
a randomized trial in 2020. they looked at patients with a heart condition called atrial fibrillation
and who were also regular drinkers. they asked half of them to just say no for six months. yeah
if that was here in portugal you couldn't get people to stop for like six hours. it wasn't easy
in australia either, in order to carry out the trial they had to eliminate 70 percent of their
volunteers because they wouldn't even consider not drinking, so you see how hard these trials can be
but they were able to complete the trial and in the group asked to cut back average intake came
down from 17 drinks a week, that's a little over two a day, to two a week, an almost ninety percent
reduction. impressive. and the heart condition was significantly improved in the group that cut back
so those results suggest a benefit of reducing alcohol, even from a consumption level around the
moderate range, at least for people who already have heart issues to begin with. okay, what about
healthy people? well, this study can't address that, and also we don't want to base public health
on individual studies, you always want to see a body of evidence to be sure. so if these trials
are so difficult to carry out, what else can we do? crafty scientists figured out a way to simulate a
randomized trial by looking at the genes we carry. if some genes cause us to drink more
then we can look at people carrying those genes which tells us something about alcohol intake
this technique was named after gregor mendel, the father of genetics and philip seymour hoffman
look-a-like. they called it mendelian randomization because genes are randomly assigned to the sperm and the egg that later meet to become you and me
meaning that which set of genes we inherit from each of our parents is a lottery. it's random.
this element of randomness is crucial because it reduces a lot of the confounders in traditional epidemiology.
carrying the gene is not a choice so the results are less confounded by other lifestyle factors.
for example, if i choose to moderate my drinking because of health concerns, it's likely i'm also doing other things that i also perceive as being healthier,
like exercising more, smoking less, eating better etc. but if i happen to just carry a gene that, for example, makes me sick when I drink,
then that's much less likely to involve other lifestyle factors, as long as the effect of the gene is specific to drinking. we'll come back
to this in a minute. so mendelian randomization is the closest thing to a randomized controlled trial
without the enormous costs and the logistical nightmare. such a study
was just published last week. they used mendelian randomization to ask if moderate alcohol intake
is indeed cardio protective. their results were striking. so striking that a renowned cardiologist
at the cleveland clinic said "this study totally changes my life". now, rather than go straight
into the study, i thought we'd do something a little different. in science, discoveries rarely
happen in a vacuum, it's more like a gradual accumulation of evidence in a given direction
way less exciting for media headlines and social media fights but it gives us more confidence. so
let's look at the build-up to this study, which will make more sense and we'll understand better
what they figured out and it's also a window into how science works. okay, let's travel
back in time all the way to 2011. at this point, a decade ago, so many observational studies had
shown the cardio protective association, that U curve, that some experts were convinced.
one of the lead scientists at the national institute on alcohol abuse and alcoholism declared
that "there have been enough studies showing the heart-healthy benefits of moderate alcohol. now
it's time to focus on why alcohol is good for the heart". let's just say that unlike some good wine,
this statement has not aged well. only three years later, in 2014, the first big shock wave was to hit
this research field. an international team looked at people carrying a mutation
in alcohol dehydrogenase, one of the key enzymes breaking down alcohol in our body. people carrying
this mutation are worse at metabolizing alcohol, they get flushed after drinking and they tend
to drink less overall. the researchers found carriers of this mutation indeed drank less
and had lower risk of coronary heart disease across categories of alcohol consumption, including
moderate and light drinkers, so individuals with a genetic predisposition to consume less alcohol
had lower, not higher, odds of developing coronary heart disease, regardless of whether they were
light, moderate or heavy drinkers. this suggested reduction of alcohol consumption even for light to
moderate drinkers is beneficial for cardiovascular health, in direct contradiction to the u-curve idea
in science, after a paradigm shifting discovery like that, you want to see confirmation, but
we would have to wait another five years before another test of this idea emerged
in 2019, a team from china analyzed the drinking habits of half a million people and they looked
at mutations in different genes, alcohol dehydrogenase, same as the previous study
and aldehyde dehydrogenase, a different enzyme in the same pathway. they used both approaches side
by side, traditional epidemiology and mendelian randomization. in traditional epidemiology they
saw the typical u-curve, the population who drank moderately, one to two drinks a day, tended to have
the least strokes. lower than heavy drinkers and lower than non-drinkers. but mendelian
randomization told a very different story. a straight line. the lower the genetic propensity to
drink, the lower the risk. the authors concluded the apparently protective effects of moderate alcohol
are largely non-causal. in other words, because the genetic experiment is less prone to confounders
the u-curve may be an artifact caused by other healthy habits in those same people who drink
moderately rather than being caused by the alcohol itself. so this is suggesting that unlike the idea
of the u-curve, not drinking maybe even more cardio protective than drinking moderately
this study had two strengths, first it showed the effect in a different ethnicity, the previous study
was in a european population and this one was in china so that adds some confidence that
it's a real effect reproducible across cultures and ethnicities, and second in this population
there was a huge gender disparity with regards to drinking, with men doing the bulk of the drinking
and almost 100% of women being non-drinkers. and accordingly, the benefit of carrying the mutations
was only seen in men, not women, so this adds some confidence that the benefit of these genes really
is reducing alcohol intake, which in women had no effect since they don't drink to begin with
rather than the genes affecting some unspecific physiological phenomena. on the other hand there
were a couple of weaknesses, first the effect on stroke was significant but the effect on
myocardial infarctions, on heart attacks, was not, possibly because the total number of myocardial
infarctions was too low to pass statistical tests. another caveat was that the participants drank
mainly spirits, so the effects of other drinks like wine could not be assessed. remember the meat video
from a couple weeks ago? there's no such thing as a perfect study, we add them all up to increase
confidence. and speaking of imperfect, people often smoke when they drink so maybe people who drink
more have more cardiovascular disease because of the tobacco that goes with it, not the alcohol
itself. fast forward to 2020, two years ago, where this study asked that exact question, also using
mendelian randomization. they found that alcohol retained its association, even after accounting
for smoking, on coronary heart disease, and they could not find a cardioprotective role of alcohol
on cardiovascular disease, similar to the previous studies, suggesting that observational studies
identifying a cardioprotective effect of light to moderate alcohol may be due to confounders
such as healthier lifestyles. so you see how studies build on top of each other,
right? to fill the gaps and to answer increasingly detailed questions and to raise confidence. and
that's where our recent study comes in, the one that changed the life of that famous cardiologist
in the present. or almost. last week. some of their findings will now be familiar to you
in traditional epidemiology they found the u-curve. moderate drinking, about five drinks a week, had
the lowest risk of coronary artery disease. but mendelian randomization showed a different picture
risk went up continuously with alcohol intake. the innovation in this study was a more sophisticated
type of analysis, which showed for the first time that the effect is not a straight line
like we saw in some of the older studies, it's exponential. risk always goes up, unlike the u
curve, but the rise is subtle at first and as the dose increases the effect becomes stronger
and stronger. they concluded that alcohol consumption of all amounts was associated
with increased risk, with marked differences across levels of intake. also, unlike in the chinese study,
here most of the alcohol consumed was beer, wine and champagne, suggesting that risk is not specific
to strong drinks like spirits. so this is where the science is at the moment. this doesn't give us 100%
certainty. nothing ever does. and every study has some weaknesses, some blind spots, some uncertainty
like every study ever, and also the more specific the question, the harder it is to answer, like "i
drink wine but it's specifically chardonnay and it's three times a week after dinner, does that
raise my risk?". nobody can tell you that with certainty. because mendelian randomization
is generally more reliable than traditional epidemiology, what the balance of evidence is
telling us is that there may be no sweet spot at moderate intake, unlike what we used to think. now,
the current recommendations by the usda are to not go over two drinks in a day for men and one
for women. i suspect this will change and will be tightened in the next edition coming out in 2025
we'll find out. so hopefully this information helps you make your informed decisions
one option out there that might work for some people are non-alcoholic wines and beers, i don't
know too much about them so if you've tried them by all means let us know below what you thought
hit or flop. interestingly, the demise of the u-curve we watched today is something very
common in nutrition so you can start to see those patterns. u-curves have also been suggested with
salt intake and with serum cholesterol levels, and in both cases the strongest evidence indicates
the u curves are also an artifact. we covered the u curve for cholesterol in this video
and we have a video in planning on salt intake so stay tuned, take care, see you next time, bye