Intake of phytosterols from natural sources and risk of cardiovascular disease in the European Prospective Investigation into Cancer and Nutrition-the Netherlands (EPIC-NL) population

Background Phytosterols (PSs) are known to lower low-density lipoprotein cholesterol (LDL-C), an established risk factor for cardiovascular disease (CVD). Whether a high intake of PS reduces CVD risk is unknown. This observational study aimed to investigate the associations between intake of naturally occurring PSs, blood lipids and CVD risk. Methods The study included 35,597 Dutch men and women, participating in the European Prospective Investigation into Cancer and Nutrition-the Netherlands (EPIC-NL) study. At baseline, intakes of naturally occurring PSs were estimated with a validated food frequency questionnaire and non-fasting blood lipids were measured. Occurrence of CVD, coronary heart disease (CHD) and myocardial infarction (MI) was determined through linkage with registries. Results The average energy-adjusted PS intake at baseline was 296mg/d (range: 83-966mg/d). During 12.2 years of follow-up, 3047 CVD cases (8.6%) were documented. After adjustment for confounders, PS intake was not associated with risk of CVD, CHD or MI (p-value trend>0.05); hazard ratios ranged from 0.90-0.99 for CVD, from 0.83-0.90 for CHD and from 0.80-0.95 for MI risk across quintiles of PS intake and were almost all non-significant. Higher PS intake was associated with lower total cholesterol (-0.06mmol/l per 50mg/d; p-value=0.038) and lower LDL-C (-0.07mmol/l; p-value=0.007), particularly among men. In mediation analysis, LDL-C did not materially affect the association between PS intake and CVD risk. Conclusions In this population with a relatively narrow range of low naturally occurring PS intakes, intake of PS was not associated with reduced CVD risk despite lower LDL-C concentrations in men.