Dozens of papers have shown an association between low LDL cholesterol levels and an increased risk of death (for example, PMID: 33293274), now for over half a century. Yet we are told that lower LDL cholesterol is good for us. Which is it? Why do doctors and scientists advise the reduction of cholesterol if lower cholesterol causes a higher risk of death?

In this podcast, I explain the association between low LDL cholesterol and an increased risk of mortality. Specifically, it is probably due to confounding by age-related chronic illnesses, which in turn causes a reduction in eat, and therefore calorie restriction and malnutrition (PMID 33293274) and therefore reduced cholesterol (PMID 4828569, 15096581). I explain that weight loss near the end of life is a normal part of age-related disease, probably universal in mammals, and that weight loss indeed does indicate the end of life (PMID 24941891). In other words, chronic illness causes death, but it also causes malnutrition weight loss which causes low cholesterol. The lower cholesterol levels and the higher risk of death are each independently caused by chronic illness, rather than the higher risk of death being caused by the lower cholesterol.

We know this especially by meta-analysis of randomized controlled trials looking at the effect of cholesterol-lowering medications on the risk of death. These trials very conclusively show that cholesterol-lowering medications directly reduce the cause of death (PMID 28444290, 29677301).

So while chronic illness may reduce cholesterol levels, chronic illness has a much more deleterious effect on risk of death than the reduction of cholesterol has. Direct reduction of cholesterol is beneficial. Cardiovascular disease is the leading cause of death in the United States (as well as erectile dysfunction). Therefore, all else equal, when one can reduce cholesterol, one should do so to optimize cardiovascular disease risk.

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