Abstract
BACKGROUND: Phytosterols are structurally similar to cholesterol and partially inhibit intestinal absorption of cholesterol, although their impact on coronary artery disease (CAD) risk remains to be elucidated. OBJECTIVES: This study aimed to prospectively assess the associations between total and individual phytosterol intake and CAD risk in United States health professionals. METHODS: The analysis included 213,992 participants from 3 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 y since baseline. Associations between phytosterol intake and the risk of CAD, such as nonfatal myocardial infarction and fatal CAD, were evaluated using Cox proportional hazards regression models. RESULTS: More than 5,517,993 person-years, 8725 cases with CAD were documented. Comparing extreme quintiles, pooled hazard ratios (95% CIs) of CAD 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 β-sitosterol. Nonlinear associations were observed for total phytosterols, campesterol, and β-sitosterol: the risk reduction plateaued at intakes above ∼180, 30, and 130 mg/d, 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 concentrations of total cholesterol, triglycerides, high-density lipoprotein cholesterol, and IL-6 and positively associated with adiponectin, whereas no significant associations were observed for low-density lipoprotein cholesterol or C-reactive protein concentrations. CONCLUSIONS: Higher long-term intake of total and major subtypes of phytosterols may be associated with a modest reduction in CAD risk, displaying a nonlinear relationship that plateau at moderate intake levels. The role of phytosterols in preventing CAD warrants further investigation.