lower cholesterol levels in the blood associate with higher risk of death. why is that,
and does that mean I should try to keep my cholesterol level high? we've talked
about this a couple times in the past and we actually made a whole video about it
over two years ago, so an older video, but yet this still remains the number one most frequently
asked question about cholesterol on social media. I even see doctors on social media puzzled by this
phenomenon on a regular basis. so I just wanted to make a quick update on this because I just
found some evidence that I was not aware of before that I think might help settle this and I've never
seen anyone on social media discuss and show this evidence. and this is exactly how science works,
evidence builds gradually over time and it either increases or decreases your confidence in a given
direction. so just to recap real quick in case you have no idea what we're talking about here,
in several epidemiological studies looking at the relationship between blood cholesterol levels,
levels of cholesterol in the blood, and risk of death in a number of populations, they see a curve
that's shaped like a U, so kind of like a valley, with a lower point in the middle and the two ends
curving up, so death risk, risk of dying of any cause, is lowest at this point in the middle, the
valley. now, this point in the middle is a total cholesterol of about 230 milligrams per deciliter,
which is considered high. 200 is normally the cutoff, under 200 is considered normal and
over 200 is considered hypercholesterolemia, high cholesterol. now, from that valley, as
the cholesterol level goes up even more, risk of death goes up, that's not incredibly surprising,
but as the cholesterol level comes down into the normal range, risk of death also goes up.
so this is very puzzling when you see it for the first time, and in fact this is often referred to
as the cholesterol paradox. the paradox of course being that levels of cholesterol that are thought
to be healthy are associated with higher risk of death. now, in the old video from two years
ago we showed that BMI, body mass index, shows a similar pattern, lowest mortality at about a BMI
of 28 in some studies, which is in the overweight range. 25 is the cutoff. under 25 is normal,
over 25 is overweight and over 30 is obese. and so here again, as the BMI goes into the normal range,
under 25, mortality, risk of death, seems to go higher. again very weird observation and
this is also sometimes referred to as the Obesity Paradox. now, at the time, two or three years ago,
when we made that video, BMI was the only other example I knew of this paradox
but I've recently realized this is a lot more common than I thought. here's the curve for blood
pressure. lowest risk of death is seen around 140 to 150 millimeters mercury of systolic blood
pressure, the higher number in your reading. but that's high blood pressure, that's hypertension.
the new guidelines consider 120 to be the cutoff. under 120 is normal, over 120 is elevated or
pre-hypertension and over 130 is hypertension. but yet again we see this pattern, with mortality
going up when blood pressure comes into the normal range. here is hemoglobin A1c, which for people
who don't know is a measure of glucose levels over three months. same pattern, mortality is
lowest in the middle range, six to eight percent hemoglobin A1c, but the cutoff for normal is 5.7.
under 5.7 is normal. so again we see mortality, risk of death, going up as hemoglobin A1c comes
down into the normal range. and this range with the lowest mortality, the valley, actually
corresponds to pre-diabetes and diabetes. so what we explained in the old video is that cholesterol
levels are lowered in all kinds of conditions and disease States. cancer, infections, liver disease,
malnutrition, malabsorption etc etc. it's a long list. so if we grab a random sample of people in a
population and their cholesterol level is low but we don't know why, their low cholesterol can be a
proxy for disease and sickness. some scientists call this the unsuspected sickness phenomenon,
so basically the lowering of cholesterol by underlying disease. so it's not that having
low cholesterol itself kills you, it's that a lot of disease states that raise risk of death also
lower cholesterol. we know the low cholesterol in all likelihood has nothing to do with the
rising mortality because if you directly lower your cholesterol by tweaking diet, with drugs,
with a cholesterol-lowering treatment like statins for example, or if you win the genetic lottery,
if you have the right genes and you have low cholesterol from birth, we don't see this rise in
mortality. in fact, if the study is large enough, enough people, long enough follow up so that you
have statistical power to detect a difference in mortality, we tend to see lower risk of death when
cholesterol is directly lowered into the healthy range. and those are much stronger data sets,
placebo-controlled double-blind randomized trials and genetic studies, much more conclusive than
these associations with the U Curves. in fact, even in these epidemiological studies that show
that U-curve, when you look specifically at people who are taking a statin for example,
who are having their cholesterol lowered by a cholesterol-lowering drug, the paradox goes away,
you do not see that association between lower cholesterol and higher death. so for people
who are actively lowering their cholesterol, low cholesterol does not associate with higher
risk of death. so the problem is not having low cholesterol, the problem is what lowered it. if
cholesterol was lowered by an underlying disease process like cancer for example, yeah that's a red
flag and it'll raise your risk of mortality. in fact, cholesterol levels gradually dropping over
the years with no obvious explanation, the person didn't clean up their diet, they're not on a drug,
can be a red flag, can be an indication to check for underlying disease like cancer,
infections etc. so all lines of evidence point in the same direction, scientifically this makes
perfect sense, but this was always a little bit confusing seeing this curve with higher death
correlating with lower cholesterol. it's scary. the realization that this pattern is common,
that we see it with BMI and blood pressure and hemoglobin A1c, this makes this point very
powerfully that this U-curve, this Association in epidemiological studies, does not mean we want to
have high cholesterol any more than it means we want to be overweight and pre-diabetic and a bit
hypertensive because of those U curves. and the explanation is likely the same for all of them,
states of disease Frailty and malnutrition like cancer, infections Etc raise our risk of death
and they also make us weaker, less well-fed, they affect our appetite, they mess up our metabolism,
and as a result these parameters often come down. there can be weight loss,
not for the right reasons, blood pressure can come down, glucose levels can come down etc. now,
let's do a thought experiment. let's say that I go on social media and I start showing these U curves
and I start arguing that we should try to be overweight and hypertensive and pre-diabetic
because of these associations and that we should just ignore our doctors´ desperate
pleas and just not worry about these high values because here's this association in all
of these epidemiological studies. I don't think I could find one soul who would get behind that.
people would just dismiss me and my message, they would just say I'm crazy and they would
immediately suspect that there's something off with these curves, that they probably don't
reflect the actual effect of these parameters. and yet when the same logic is proposed for
cholesterol, with curves that look identical, not only are people not resistant to this idea,
it seems to be welcomed. this seems to be a very popular idea on podcasts, on Twitter, on TikTok...
there's entire communities of people on the internet calling themselves cholesterol skeptics
largely on the back of data like that. I've never seen anyone calling themselves diabetes skeptics
or obesity skeptics. the idea of the cholesterol paradox, that because of these associations,
these U-shaped curves in epidemiological studies, we should try to keep our cholesterol high,
is contradicted by every line of evidence. it doesn't have a leg to stand on. it's time
to let it go. let me know your questions, your comments below, I'll see you next week