Effect of Plant Sterols on Cholesterol Oxidation Products in Statin-Treated Hypercholesterolemic Individuals: A Pilot Study

Cholesterol oxidation products (COPs) have been linked to inflammation, endothelial dysfunction, and atherosclerosis. COPs levels in hypercholesterolemic individuals are up to 50% higher than in healthy people. Although statins lower cholesterol synthesis, research demonstrates that they do not prevent an increase in COPs levels and the damage on endothelial cells. We hypothesized that plant sterols (PS) could reduce COPs concentrations, potentially offering a synergistic effect with statin treatment. This randomized, double-blind, parallel clinical trial investigates the effects of a PS-food supplement (2 g PS/d) on plasma COPs levels in statin-treated hypercholesterolemic individuals (ClinicalTrials.gov ID: NCT05901246). Twenty-six volunteers were randomly assigned to two groups and given either a PS supplement or a placebo for six weeks. Blood samples were taken before and after the treatment, and plasma was isolated. After sterol extraction and purification, COPs and cholesterol levels were analyzed by gas chromatography/mass spectrometry. There were no significant differences (p > 0.05) in plasma cholesterol (2276 ± 480 in control and 2169 ± 735 μg/mL in PS-treated subjects), total (1.12 ± 0.26 in control and 1.47 ± 0.48 μg/mL in PS-treated subjects) and single (α-epoxy-cholesterol, β-epoxy-cholesterol, cholestanetriol, 7α-hydroxy-cholesterol, 7β-hydroxy-cholesterol, and 7-keto-cholesterol) COPs levels between the two groups after the intervention; moreover, these levels were not associated with physical or dietary habits. These findings suggest that PS supplementation did not measurably reduce COPs concentrations over six weeks in this small sample of statin-treated individuals with relatively stable cholesterol levels. Future studies should explore the mechanisms underlying the interaction between statins, PS, and cholesterol oxidation to improve strategies for managing CVD risk.