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Cholesterol and mortality: Evidence of a U-shape Relationship

nature.com

51–60 of 66 posts

Re: Cholesterol and mortality: Evidence of a U-shape Relationship

#51
post #47

Earlier quoted context omitted.

> Yes, this is a necessary consequence of the first observation. Not necessarily. The cholesterol could be redundant.

No, that's not the case. If your natural weight is 150 pounds, but you've gotten to the point where you contain 700 pounds of cholesterol, you'll die.

I was referring to the lower bound.

Re: Cholesterol and mortality: Evidence of a U-shape Relationship

#52
post #12

I wonder how this would look if we consider LDL, HDL and triglycerides individually... Perhaps that would be more telling than just considering total cholesterol.

Diet is also a factor. Nicotinic Acid (vitamin B3) will lower Cholesterol because it converts cholesterol into hormones starting with Pregnenolone, 500mg of nicotinic acid on an empty stomach or fat free meal is the fastest cheapest way to get a growth hormone boost, if you can handle the prostaglandin 9sun burn) flush! https://en.wikipedia.org/wiki/Steroid_hormone#/media/File:St... Manganese also affects cholesterol…

The part about B3 sounds very interesting but whats a prostaglandin flush?

Re: Cholesterol and mortality: Evidence of a U-shape Relationship

#53
post #14

This is not a new finding. It's common enough to have a name: the cholesterol paradox ( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374572/ ). Also replicated in a more recent n=100k Denmark study: https://www.bmj.com/content/371/bmj.m4266 These are all observational studies, meaning cause and effect is not established. It's relevant that people with some cancers will have very low cholesterol (the cancer apparentl…

"...there are no strong theories for the diseases caused by low cholesterol..." Well, the body has a whole mechanism for manufacturing cholesterol, so it must be good for something. It seems obvious that there's some level at which low cholesterol must cause death. A U-shaped cholesterol-mortality curve is pretty much guaranteed to exist. The only question is where the minimum is.

Hemorrhagic stroke is a leading candidate for the mechanism of low cholesterol induced mortality. It is a known side effect of statins, albeit rare.

Re: Cholesterol and mortality: Evidence of a U-shape Relationship

#54
post #51

Earlier quoted context omitted.

No, that's not the case. If your natural weight is 150 pounds, but you've gotten to the point where you contain 700 pounds of cholesterol, you'll die.

I was referring to the lower bound.

You think we have a working system producing a substance that is only ever harmful?

If it's ever helpful, that's already guaranteed to produce a U-shaped curve. Just like I say in the quote you pull.

(It's theoretically possible that mortality won't go to 100% at zero cholesterol. But that's not the quote you pulled.)

Re: Cholesterol and mortality: Evidence of a U-shape Relationship

#55
post #14

This is not a new finding. It's common enough to have a name: the cholesterol paradox ( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374572/ ). Also replicated in a more recent n=100k Denmark study: https://www.bmj.com/content/371/bmj.m4266 These are all observational studies, meaning cause and effect is not established. It's relevant that people with some cancers will have very low cholesterol (the cancer apparentl…

"...there are no strong theories for the diseases caused by low cholesterol..." Well, the body has a whole mechanism for manufacturing cholesterol, so it must be good for something. It seems obvious that there's some level at which low cholesterol must cause death. A U-shaped cholesterol-mortality curve is pretty much guaranteed to exist. The only question is where the minimum is.

Right, but this is blood cholesterol concentration, not total body cholesterol.

Re: Cholesterol and mortality: Evidence of a U-shape Relationship

#56
post #12

I wonder how this would look if we consider LDL, HDL and triglycerides individually... Perhaps that would be more telling than just considering total cholesterol.

Well, we already have PCSK9 inhibitors, which came about because people with PCSK9 mutations have very low LDL levels as well as very low risk of coronary artery disease.

So it appears that you can drive LDL levels quite low without harm.

https://en.wikipedia.org/wiki/PCSK9

Re: Cholesterol and mortality: Evidence of a U-shape Relationship

#57
post #51

Earlier quoted context omitted.

I was referring to the lower bound.

You think we have a working system producing a substance that is only ever harmful? If it's ever helpful, that's already guaranteed to produce a U-shaped curve. Just like I say in the quote you pull. (It's theoretically possible that mortality won't go to 100% at zero cholesterol. But that's not the quote you pulled.)

If substance X produces Z and substance Y produces Z, then removing X still gives you Z. Or, removing a substance that is produced by the body does not necessarily leads to mortality.

I'm not saying that Y exists, just that the argument is either incomplete or the logic unsound.

Re: Cholesterol and mortality: Evidence of a U-shape Relationship

#58
post #39
post #34

Earlier quoted context omitted.

> However, logically my post does not entirely rely on knowing the precise in vivo mechanism of statins and their causal health effects. We only need to see that in RCTs, lowered cholesterol doesn't cause increased mortality as these observational studies would suggest. That is a pretty direct test of the null hypothesis. It doesn't quite prove that, though. It proves that statins do not increase mortality risk on ne…

> it doesn't prove that reducing cholesterol by other means wouldn't increase mortality risk. It's possible, for instance, that lower cholesterol does increase mortality, but that statins are offsetting that increase in some other way. It's within the realm of possibility, but very unlikely given the state of the evidence. Ok, ignore statins because that seems to be a trigger. Another way to test this hypothesis is t…

That's just one disease, that one wouldn't expect to be associated with low cholesterol to begin with, though.

Re: Cholesterol and mortality: Evidence of a U-shape Relationship

#59
post #58
post #39

Earlier quoted context omitted.

> it doesn't prove that reducing cholesterol by other means wouldn't increase mortality risk. It's possible, for instance, that lower cholesterol does increase mortality, but that statins are offsetting that increase in some other way. It's within the realm of possibility, but very unlikely given the state of the evidence. Ok, ignore statins because that seems to be a trigger. Another way to test this hypothesis is t…

That's just one disease, that one wouldn't expect to be associated with low cholesterol to begin with, though.

There exist MR studies on cholesterol levels vs. longevity as well: https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bcp....

These nits really aren't worth picking over when you haven't presented any RCT or MR evidence for your alternative theories.

Re: Cholesterol and mortality: Evidence of a U-shape Relationship

#60
post #57

Earlier quoted context omitted.

You think we have a working system producing a substance that is only ever harmful? If it's ever helpful, that's already guaranteed to produce a U-shaped curve. Just like I say in the quote you pull. (It's theoretically possible that mortality won't go to 100% at zero cholesterol. But that's not the quote you pulled.)

If substance X produces Z and substance Y produces Z, then removing X still gives you Z. Or, removing a substance that is produced by the body does not necessarily leads to mortality. I'm not saying that Y exists, just that the argument is either incomplete or the logic unsound.

Well, the body can utilize energy by either an aerobic or anaerobic pathway, but that doesn't mean we'd be fine if either of these pathways were disabled. We'd die without the aerobic pathway and have much reduced capabilities (probably fatal too, I'd guess - certainly if a tiger is chasing you) without the anaerobic pathway.

If a mechanism has been produced/preserved by natural selection, it's hard to believe that disabling it wouldn't lead to death (or infertility), or to serious debilitation (also likely to lead to death, in a non-benign environment).

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