Evaluation of the efficacy of plant sterols supplement sterolip® ESI in patients with type IIA hypercholesterolemia in relation to Genetic variants modulating intestinal absorption of cholesterol

Background and aim: Phytosterols (PS) are recommended by European Guidelines for the treatment of hypercholesterolemia. This study aims to evaluate the lipid-lowering activity of a PS supplement (STEROLIP® ESI) in subjects with hypercholesterolemia and the influence of genetic variants involved in cholesterol absorption in the modulation of the individual response to PS. Methods: 60 subjects suffering from hypercholesterolemia were randomized to PS supplement STEROLIP® 1.6g/day or to placebo for 6 weeks, and subsequently they were all switched to the supplementation with PS for another 6 weeks. At baseline and every 3 weeks, anthropometric measures and lipid profile were collected. All patients were also genotyped for three genetic polymorphisms involved in intestinal cholesterol absorption (APOE, NPC1L1 and ABCG8). Results: After 3 weeks, TC and LDL-C were significantly lower in PS group. In the 28 patients treated for 12 weeks with PS, we obtained the highest effect after 9 weeks (-8.3% for TC and -12% for LDL-C). We observed a greater reduction of TC and LDL-Cin subjects carrying the E4 allele of APOE gene, in homozygous subjects for the rare allele of NPC1L1 rs2072183 polymorphism and in heterozygous carriers of rare allele rs11887534 in ABCG8 gene than in other genotypes. Conclusion: This study confirms the lipid-lowering effect of PS that is maintained even in the midterm. We highlighted that genetic variants influencing the intestinal cholesterol absorption can contribute to the inter-individual variability of the response of PS supplementation