Effects of Plant Sterol Supplementation on Inflammation, Endothelial Dysfunction, and Oxidative Stress in Adults with Overweight or Obesity and Mild Hypercholesterolemia: A Randomized, Double-Blind, Placebo-Controlled Crossover Trial

Objective: To evaluate the effects of plant sterol (PS) supplementation on inflammation, endothelial dysfunction and oxidative stress in subjects with overweight/class I–III obesity and mild hypercholesterolemia. Methods: Randomized, double-blind, placebo-controlled, crossover trial. Twenty-three subjects received 2 g/day of PS or placebo for 8 weeks, separated by a 6-week wash-out. LDL-cholesterol (LDL-C) was the primary outcome of the trial; all other parameters, which are the main focus of this article, were secondary and exploratory outcomes. Results: PS supplementation increased serum β-sitosterol (+1.21 µg/mL [95% CI 0.70, 1.72]) and its cholesterol-normalized ratio (+0.60 µmol/mmol [0.35, 0.85]), the only outcomes that retained significance after false discovery rate (FDR) correction. Campesterol showed a nominal increase (+0.72 µg/mL [0.10, 1.35]) that did not retain significance after FDR correction, whereas cholesterol synthesis markers (desmosterol and lathosterol) showed no statistically significant treatment effect. No statistically significant treatment effect was detected on LDL-C (−3.19 mg/dL [−15.91, 9.53]) or total cholesterol (−1.79 mg/dL [−14.39, 10.81]). No inflammatory, endothelial dysfunction or oxidative stress biomarker showed a statistically significant treatment effect after FDR correction, VCAM-1 being the only parameter with a nominal treatment effect (+59.08 ng/mL [7.14, 111.02]). Cholesterol-normalized ratios of four cholesterol oxidation products (COPs) decreased within the PS arm but not versus placebo. Inverse Pearson correlations of PS absorption markers with IL-1β, IL-12p70 and ICAM-1 (r = −0.56 to −0.49) were not reproduced by Spearman analysis and did not retain significance after FDR correction. No clear correlation was found between serum PS and oxidative stress markers. Conclusions: PS supplementation increased circulating β-sitosterol concentrations, but no statistically significant effects were detected on LDL-C or the measured inflammatory, endothelial dysfunction, or oxidative stress biomarkers. Larger studies are needed to clarify the effects of PS supplementation on these outcomes.