Phytosterols and Phospholipids Synergistically Improve Lipid Metabolism and Oxidative Stress: Evidence From Animal Model and Human Randomized Controlled Trials

ABSTRACT This study aimed to evaluate the effects of phytosterols (PSs), alone or in combination with phospholipids (PLs), on dyslipidemia and oxidative stress, using both a high‐fat diet‐induced rat model and a randomized controlled trial in individuals with borderline hypercholesterolemia. In the animal study, Sprague‐Dawley rats were divided into five groups (control, model, PS, PL, and PS+PL) and treated for 8 weeks. The PS+PL combination significantly reduced body weight, liver index, and serum glutathione peroxidase activity, while improving hepatic and adipose morphology. In the human trial, 82 participants were randomized into PS, PS+PL, or placebo groups and treated for 2 months in a triple‐blind, parallel‐design trial. Both PS and PS+PL groups showed significant reductions in total cholesterol, low‐density lipoprotein cholesterol, alanine aminotransferase, reactive oxygen species, and lipid peroxidation, along with improvements in antioxidant enzyme and lipase activities. The PS+PL group showed additional effects, including reduced apolipoprotein B and lactate dehydrogenase levels, demonstrating superior efficacy compared to PS alone. In conclusion, PSs, particularly when combined with PLs, effectively improve cholesterol profile and oxidative stress parameters. These findings highlight the potential translational benefits of PS+PL as a functional dietary intervention for managing borderline hypercholesterolemia.