Phytosterol Intake and Risk of Coronary Heart Disease: Results from Three Prospective Cohort Studies.

BACKGROUND: Phytosterols are structurally similar to cholesterol and partially inhibit intestinal absorption of cholesterol, although their impact on coronary heart disease (CHD) risk remains to be elucidated.

OBJECTIVE: To prospectively assess the associations between total and individual phytosterol intake and CHD risk in U.S. health professionals.

METHODS: The analysis included 213,992 participants from three prospective cohorts-the Nurses' Health Study (NHS), NHSII, and Health Professionals Follow-Up Study-without cardiovascular disease or cancer at baseline. Diet was assessed using a validated food frequency questionnaire every 2-4 years since baseline. Associations between phytosterol intake and the risk of CHD, including nonfatal myocardial infarction and fatal CHD, were evaluated using Cox proportional hazards regression models.

RESULTS: Over 5,517,993 person-years, 8,725 CHD cases were documented. Comparing extreme quintiles, pooled hazard ratios (95% CIs) of CHD were 0.93 (0.86, 1.01; P-trend=0.16) for total phytosterols, 0.89 (0.82, 0.96; P-trend=0.05) for campesterol, 0.95 (0.88, 1.02; P-trend=0.10) for stigmasterol, and 0.92 (0.85, 1.00; P-trend=0.09) for beta-sitosterol. Nonlinear associations were observed for total phytosterols, campesterol, and beta-sitosterol: the risk reduction plateaued at intakes above ∼180 mg/day, 30 mg/day, and 130 mg/day, respectively (P-nonlinearity<0.001). In a subset of participants (N range between 11,983 and 22,039), phytosterol intake was inversely associated with plasma levels of total cholesterol, triglycerides, HDL cholesterol, and interleukin-6 and positively associated with adiponectin, while no significant associations were observed for LDL cholesterol or C-reactive protein levels.

CONCLUSIONS: Higher long-term intake of total and major subtypes of phytosterols may be associated with a modest reduction in CHD risk, displaying a non-linear relationship that appeared to plateau at moderate intake levels. The role of phytosterols in preventing CHD warrants further investigation.