Phytosterols (PSs) have been proposed as dietary means to lower plasma
LDL-C. However, concerns are raised that PSs may exert atherogenic effects, which would offset this benefit.
Phytosterolemia was thought to mimic increased plasma PSs observed after the consumption of PS-enriched foods. This expert statement examines the possibility of specific atherogenicity of PSs based on
sterol metabolism, experimental, animal, and human data. Observational studies show no evidence that plasma PS concentrations would be associated with an increased risk of
atherosclerosis or cardiovascular (CV) events. Since variants of the ABCG5/8 transporter affect the absorption of
cholesterol and non-
cholesterol sterols, Mendelian randomization studies examining the effects of ABCG5/8 polymorphisms cannot support or refute the potential atherogenic effects of PSs due to pleiotropy. In homozygous patients with
phytosterolemia, total PS concentrations are ~4000% higher than under physiological conditions. The prevalence of
atherosclerosis in these individuals is variable and may mainly relate to concomitant elevated
LDL-C. Consuming PS-enriched foods increases PS concentrations by ~35%. Hence, PSs, on a molar basis, would need to have 20-40 times higher atherogenicity than
cholesterol to offset their
cholesterol reduction benefit. Based on their
LDL-C lowering and absence of adverse safety signals, PSs offer a dietary approach to
cholesterol management. However, their clinical benefits have not been established in long-term CV endpoint studies.