The effect of phytosterol supplementation on endothelial function in adults: a systematic review and dose-response meta-analysis of randomized controlled trials

Abstract

Abstract

While the cholesterol-lowering properties of phytosterols are well established, their effects on cardiovascular health, particularly endothelial dysfunction and low-grade inflammation, remain insufficiently explored. This meta-analysis aimed to evaluate the impact of phytosterol supplementation on endothelial function in adults using key vascular biomarkers. A systematic search of major databases up to March 2026 identified randomized controlled trials comparing phytosterol supplementation with placebo or control. Eligible studies assessed endothelial function using flow-mediated dilation (FMD) or markers of endothelial activation, such as vascular cell adhesion molecule-1 (VCAM-1). Random-effects models were applied to pool effect sizes, and subgroup and dose-response analyses were performed. Ten randomized controlled studies (14 effect sizes; 1,278 participants) were included, comprising six studies contributing eight effect sizes for FMD ( n = 802) and four studies contributing six effect sizes for VCAM-1 ( n = 476). Phytosterol supplementation showed no significant effect on FMD (mean difference: -0.05%, 95% CI: -0.61 to 0.51; P = 0.857) or VCAM-1 (standardized mean difference: -0.16, 95% CI: − 0.34 to 0.03; P = 0.098). Dose-response and meta-regression analyses indicated no significant association of either dose or treatment duration with endothelial outcomes (all P > 0.3). Based on current evidence, no statistically significant effect of phytosterol supplementation on endothelial function was observed. Further long-term, well-designed randomized trials, particularly in high-risk populations, are required to better elucidate potential vascular effects.