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Cholesterol and mortality: Evidence of a U-shape Relationship

nature.com

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

#11
post #2

Can someone tl;dr? Not that the paper is too long, but I think I'd need to go back to university and major in biology or statistics to understand what they discovered and more importantly what it might mean.

Here's the hazard graph for total cholesterol:

https://www.nature.com/articles/s41598-018-38461-y/figures/2

230 mg/dL is associated with the lowest mortality, and anything below or above that increases mortality.

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

#13
post #5

Am I the only one that seems to think there is some correlation is not causation here with the numbers?

Agreed. I'd bet money that 20 years from now, the anti-cholesterol fad will be viewed just like the anti-fat fad.

Cholesterol is an essential building/repair block that our body makes, with very little absorbed from diet.[1] Since cholesterol responsible for repairing damaged tissue in the body[2], how do we know know that inflamed, unhealthy individuals don't generate high cholesterol amounts for repair and not from an unhealthy diet? .... Time will tell.

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257636/#:~:tex....

[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4630197/

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

#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 apparently using it as fuel source), which reverts to normal in remission. Other medical conditions can lower serum cholesterol, from IBD to chronic liver disease (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3271321/).

If low cholesterol is inherently mortality inducing, lowering it directly in otherwise healthy people should cause more deaths. This is a testable hypothesis. The Denmark study found that people on statins (cholesterol lowering) did not die more, even when they were on the lower side of the U curve.

There have also been countless RCTs with statins (or other cholesterol reduction drugs) being the only controlled intervention, finding that low TC improves total mortality.

A long term study tracking change in total cholesterol found that people who always had low TC (genetically) did not have a higher risk of death, but those whose TC suddenly dropped from normal to low had a higher risk of cancer: "We observed a significant risk of cancer, noncardiovascular noncancer, and all-cause mortality in men whose TC levels changed to low (https://www.ahajournals.org/doi/10.1161/01.cir.92.9.2396)

These points together point to the low cholesterol -> high mortality link as being a biomarker of underlying disease, not a direct causal link.

(Info taken from this video: https://www.youtube.com/watch?v=CxX51n2Z0vc)

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edit: skimmed the paper, authors mention everything in this post but have some counterpoints. They point to other longitudinal studies where consistently low cholesterol was a risk factor for death (a point against the sudden lowering due to cancer hypothesis). There are many studies like this, but the problem is while we have shown the link b/w cardiovascular death and high cholesterol through RCTs, there are no strong theories for the diseases caused by low cholesterol, while we know cancer and chronic liver disease cause low cholesterol. It could just be a marker of general frailty in old age.

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

#15
post #7

Earlier quoted context omitted.

When you have TC (total cholesterol) When you have TC > 200 mg/dL - each 1mmol/L increases mortality. The confidence interval was high. > In the age groups of 18–34, 35–44, 45–54, 55–64, 65–74, and 75–99 years, each 1 mmol/L higher TC increased mortality by 14%, 13%, 8%, 7%, 6%, and 3%, respectively (P < 0.001 for each age group), for TC ≥ 200 mg/dL, while the corresponding TC changes decreased mortality by 13%, 27%,…

So basically the 170 mg/dL TC limit that my lab shows is very suboptimal, and I should go for 230 instead?

No. Please don't make health decisions off of incorrect inferences from observational studies. https://news.ycombinator.com/item?id=30893041

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

#16
post #11
post #2

Can someone tl;dr? Not that the paper is too long, but I think I'd need to go back to university and major in biology or statistics to understand what they discovered and more importantly what it might mean.

Here's the hazard graph for total cholesterol: https://www.nature.com/articles/s41598-018-38461-y/figures/2 230 mg/dL is associated with the lowest mortality, and anything below or above that increases mortality.

> increases mortality

Implies a causal relationship. In reality, it's much more likely that causality points the other way, and an underlying disease like cancer is causing low cholesterol: https://www.ahajournals.org/doi/10.1161/01.cir.92.9.2396

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

#17
post #16
post #11

Earlier quoted context omitted.

Here's the hazard graph for total cholesterol: https://www.nature.com/articles/s41598-018-38461-y/figures/2 230 mg/dL is associated with the lowest mortality, and anything below or above that increases mortality.

> increases mortality Implies a causal relationship. In reality, it's much more likely that causality points the other way, and an underlying disease like cancer is causing low cholesterol: https://www.ahajournals.org/doi/10.1161/01.cir.92.9.2396

That's interesting, thank you.

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

#18
post #5

Am I the only one that seems to think there is some correlation is not causation here with the numbers?

No, scientists have studied this phenomenon for decades. This is a study specifically interrogating the direction of causality for low cholesterol and mortality: https://www.ahajournals.org/doi/10.1161/01.cir.92.9.2396

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

#20
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. https://pubmed.ncbi.nlm.nih.gov/3705654/ "a favourable influence of manganese was shown which effected a decrease of the cholesterol content of serum, liver and aorta and inhibited the entry of lipids into the aorta. The influence of the manganese on various enzymes as well as a manganese-copper interaction are discussed as possible causes." Manganese is one of those minerals in constant decline from birth when Reactive Oxygen Species starts, before then we all get about 9months to build up levels in the body, provided the mother is healthy and has an healthy diet.

And there isnt much discussion on the content of HDL. https://en.wikipedia.org/wiki/High-density_lipoprotein#Overv...

And on the point of macrophage accumulation, no mention of how vit K1 keeps calcium out of tissue which prevents elastic fibres from hardening and thus causing their own problems.

Thing is whatever science looks at can be portrayed in a positive or negative light.

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