> 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 to look at people with polymorphisms in their lipid regulation genes that cause different cholesterol levels, ranging from familial hypercholesterolemia to the opposite, lifelong low cholesterol. Drugs don't come into this, so it's not an intervention trial or RCT, but it's called a Mendelian randomization trial. Here's one: https://www.jacc.org/doi/full/10.1016/j.jacc.2012.09.017
> All 9 polymorphisms were associated with a highly consistent reduction in the risk of CHD per unit lower LDL-C, with no evidence of heterogeneity of effect (I2 = 0.0%). In a meta-analysis combining nonoverlapping data from 312,321 participants, naturally random allocation to long-term exposure to lower LDL-C was associated with a 54.5% (95% confidence interval: 48.8% to 59.5%) reduction in the risk of CHD for each mmol/l (38.7 mg/dl) lower LDL-C. This represents a 3-fold greater reduction in the risk of CHD per unit lower LDL-C than that observed during treatment with a statin started later in life (p = 8.43 × 10−19).
