Discussion of a Norwegian study looking at 50,000 people who didn't have pre-existing heart disease for ten years. http://drmalcolmkendrick.files.wordpress.com/2012/09/mortality-and-cholesterol1.png?w=600&h=309

As you can see, for women the story is very straightforward indeed. The higher the cholesterol level, the lower the risk of overall mortality. With regard to heart disease alone, the highest risk is at the lowest cholesterol level. For men there is more of a U shaped curve, but overall mortality is highest at the lowest cholesterol level.

Here's the study.

Here's the actual conclusion from the study, which dhoe pointed out in comments is considerably milder than the quote above:

Based on epidemiological analysis of updated and comprehensive population data, we found that the underlying assumptions regarding cholesterol in clinical guidelines for CVD prevention might be flawed: cholesterol emerged as an overestimated risk factor in our study, indicating that guideline information might be misleading, particularly for women with ‘moderately elevated’ cholesterol levels in the range of 5–7 mmol L-1. Our findings are in good accord with some previous studies. A potential explanation of the lack of accord between clinical guidelines and recent population data, including ours, is time trend changes for CVD/IHD and underlying causal (risk) factors.

‘Know your numbers’ (a concept pertaining to medical risk factor levels, including cholesterol) is currently considered part of responsible citizenship, as well as an essential element of preventive medical care. Many individuals who could otherwise call themselves healthy struggle conscientiously to push their cholesterol under the presumed ‘danger’ limit (i.e. the recommended cut-off point of 5 mmol L-1), coached by health personnel, personal trainers and caring family members. Massive commercial interests are linked to drugs and other remedies marketed for this purpose. It is therefore of immediate and wide interest to find out whether our results are generalizable to other populations.

However, the chart (the png link above-- I don't know how to make the image appear) shows that the all cause mortality for women was lower if their cholesterol results were higher.

A different big study which also found that low cholesterol was dangerous, but high cholesterol was also dangerous in terms of heart attacks, though mostly for men under fifty, and (I think) not so much for women.

A comment explains that the usual test for cholesterol isn't actually for cholesterol, it's for the lipoproteins which keep all sorts of fat molecules from forming large blobs in a watery environment.

This sort of thing appeals to a number of my prejudices, so I'm hoping to get some more meticulous angles on it from LW.

Post edited to add discussion of the conclusion of the Norwegian study.

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I may have missed it on my cursory glance, but a possible confounder is not checking for the presence of cholesterol lowering medication. Those would "artificially" lower cholesterol scores while not decreasing the risk to the levels of someone who naturally has low cholesterol levels.

Edit: One of the staples for any aspiring contrarian in the medical community: Controversy surrounding the lipid hypothesis


This (admittedly biased) youtuber has a pretty thorough criticism of the study. The bottom line is that cholesterol tends to drop off before death (6:26 in the video), not just because cholesterol-lowering medications are administered to those at highest risk of heart attack (as Kawoomba points out), but also because of other diseases. When you correct for this, or follow people throughout their lives, this reverse causation effect disappears, and you find exactly the association you would expect: higher cholesterol associates with higher cardiovascular and total mortality (10:21).

I think that studies like this one are like studies showing that overweight is "protective" against mortality - when the obvious alternative explanation is that smoking, cancer, and other diseases can prevent weight gain, or cause weight loss, just before they kill you! Obviously, this would mask or even reverse the association between overweight (high cholesterol) and death, even if overweight (high cholesterol) causes death.

It's a good theory and the priors for it being true are high, but the one study that should have been able to test it directly got the opposite results as the theory would have predicted; patients with consistently low cholesterol over twenty years had higher mortality rate than patients with sudden drops in cholesterol.

One study isn't enough to draw any conclusions, but it does prevent me from considering the issue completely solved despite the elegance of this explanation.

Fascinating. But note that these are still very old people with declining cholesterol as they age. The study is more relevant to physicians deciding whether to prescribe statins to their elderly patients, and less relevant to young people deciding whether to keep cholesterol low throughout life with diet.

I'd need to read the whole study, but what I see so far doesn't even contradict the hypothesis I outlined. The abstract says that people who had low cholesterol at the last two examinations did worse than people who had low cholesterol at only the last examination. But most of these old people had declining cholesterol. So maybe this just means that the earlier your cholesterol starts to decline from aging, the sooner you die.

Anyway, I put more stock in the cross-cultural epidemiology and intervention trials, than in these observational studies trying to parse small differences within relatively homogeneous, free-living populations. We know that the longest-lived, healthiest populations in the world ate a low saturated-fat diet that induces low cholesterol. And we know that Dean Ornish was able to reverse heart disease with a lifestyle intervention including a cholesterol-lowering diet. Show me a population as healthy as the Okinawans with high cholesterol, or an intervention as effective as Ornish's without lowering cholesterol, and I'll reconsider. Otherwise, I do consider the issue settled from a pragmatic perspective, even if some of the academic questions remain to be answered. That is, it may be possible to have a healthy lifestyle that raises cholesterol, but we don't have any proven examples of such a lifestyle to emulate, do we? Mike Darwin gave a good explanation of this idea in "Interventive Gerontology".

I think it's already pretty-well established in medical literature that not all cholesterol is equivalent; LDL and HDL cholesterol are associated with higher and lower risks, respectively. The abstract for this study doesn't suggest they were differentiated.

More speculatively: Given this is in Norway, which non-authoritative sources on the internet suggest has an average diet consisting largely of fish, which is relatively high in HDL and low in HDL cholesterol compared to red meat, their diets would favor HDL cholesterol.

(I'm a dietary skeptic; I've seen the consensus reverse itself too frequently to take it seriously as a science, and I've seen too many people whose overall apparent health improved switching to diets which the consensus claims is unhealthy. But these seem like serious confounding issues for conclusions drawn from this study.)

The second study was of Austrians, who probably don't eat as much fish. It's interesting that, while it also found that low cholesterol is dangerous, it found somewhat more danger from high cholesterol.

At least some of the objections seem to be that low cholesterol is a common side effect of being very ill, and that lifelong low cholesterol is healthy.

This sounds as though an unexplained drop in cholesterol should be used as an indicator that a person is in trouble, just as an unexplained drop in weight should be, and also that longitudinal studies of individual health and cholesterol should be done.


The conclusion of the authors of the Norwegian study sounds quite a bit weaker: "cholesterol emerged as an overestimated risk factor in our study, indicating that guideline information might be misleading, particularly for women with ‘moderately elevated’ cholesterol (...)".

Thanks. I've added a quote of the conclusion from the study and a comment that it doesn't match a chart from the study to my post.