[superqd]

So much nutrition research is all correlation and no causation. Statements like this, which over-infer, kill me:

"There is little doubt that people with high cholesterol have an increased risk of disease."

It's just as valid to say that people with heart disease are more likely to have high cholesterol. When all you have is correlation, there is a heart disease group, and a high cholesterol group, and all you shown with correlation is that there is a third overlapping group of people with both. With only correlation, you don't know how/why, or even if, members of one group transform into the other. Which is partly the underpinning of the article.

It's possible that high cholesterol is a result of underlying heart disease (which the article says is possible), rather than a cause. But what shocks me is that people, even researchers, seem surprised to realize such possibilities.

[123409871234]

We know that high cholesterol is a cause of heart disease rather than a mere correlation because people with genetic Hypercholesterolemia have a rate of heart disease 10-20x that of the general population, independent of other risk factors: https://www.acc.org/latest-in-cardiology/articles/2020/06/01...

[tsimionescu]

Do we know that people with hypercholesterolemia don't just have a heart/blood vessel/metabolic defect that also causes high cholesterol?

[rictoo]

By definition, Familial Hypercholesterolemia is a genetic defect of the receptor responsible for clearing cholesterol-containing droplets from the blood.

[tsimionescu]

I understand that, but my point was that it's in principle possible that the exact effects of a particular genetic disease are hard to discover. Serum cholesterol is easy to measure, so it could be just the easiest to notice sign of a more complex metabolic modification induced by the specific genes. I doubt we are at a point where we can look at a gene and say exactly what it affects in the entire body.

[superqd]

That doesn't rebut my assertion or complaint at all, since you are referring to a specific type of genetic disorder.

The research in general on nutrition and hearth health is still mostly correlation. Definitely someone with a specific disorder could have a more obvious causal link with cholesterol and cardiac events, but I've read a bunch of different papers, many from respected institutions, and the conclusions usually are, IMHO (I studied physics), garbage.

[sjwright]

That's still only evidence of correlation, not causation.

[JacobSuperslav]

No we actually understand the underlying mechanisms here, to a decent extent.

In case of people who have a high level LDL cholesterol, the phagocytes - the scavenger cells in blood consume more cholesterol particles in general. The result is cholesterol is more likely to stick to the walls of affected blood vessels.

This is one of the most thoroughly researched topics in medicine.

Does it mean high LDL will always result in a heart attack? No! Just like not every cigarette smoker dies of lung cancer.

[sfink]

The "thoroughness" of the research doesn't matter much when it's based upon a false assumption or two.

You describe one mechanism by which cholesterol could cause heart disease. As you say, there is lots of evidence that it happens -- in an unknown subset of the population, with defining characteristics that nobody's managed to figure out.

The science just isn't there. And the financial success of statins seems to really get in the way of people wanting to work it all out.

[123409871234]

The molecular mechanism by which cholesterol causes heart disease is well understood, and atherosclerosis has been experimentally induced in every species of mammal ever studied by either feeding the animals a high cholesterol diet or knocking out genes related to LDL metabolism, and these results are consistent between hundreds of studies performed over the past 100 years. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4525717/