Ezetimibe alters micelle structure and reduces Niemann-Pick C1-like 1-mediated absorption of vitamins E and K1 in CaCo-2 cells

Abstract

Ezetimibe (EZE) is known to inhibit cholesterol absorption by targeting Niemann-Pick C1-like 1 (NPC1L1). However, its effects on the absorption of fat-soluble vitamins, such as Vitamin E and Vitamin K₁, remain unclear. This study investigates how EZE impacts micellar properties and vitamin absorption. We analyzed the shape, size, diffusion rate, and zeta-potential of micelles during Vitamin E and K₁ absorption. Our findings demonstrate that EZE causes micelles to transition from an elliptical to a cylindrical shape, reducing vitamin absorption efficiency. EZE also impairs absorption by altering micelle composition, hindering NPC1L1 binding, and directly blocking vitamin uptake. EZE negatively affects Vitamin E and K₁ absorption, raising concerns about potential deficiencies with long-term use. These findings highlight the need for strategies to minimize the adverse effects of EZE in clinical practice.