Evidence check: HDL in the context of longevity

HDL (high-density lipoprotein) is often called 'good cholesterol,' but the evidence for a direct causal role in longevity is moderate. Observational studies show that higher HDL-C levels are associated with lower cardiovascular mortality, yet Mendelian randomization studies and clinical trials with HDL-raising drugs (e.g., CETP inhibitors) have not demonstrated a benefit for all-cause mortality. HDL function (e.g., cholesterol efflux capacity) appears more important than concentration alone. Direct-to-consumer tests typically measure only HDL-C, not function. Genetic variants affecting HDL-C have small effect sizes and are not suitable for clinical decision-making. For longevity, lifestyle factors (diet, exercise, non-smoking) are far more impactful. The evidence level is human-moderate, with the caveat that HDL-C alone is not a reliable predictor of longevity.