The Dynamics\nof the Colloidal Interplay of Bile and\nVitamin K<sub>1</sub>

Vitamin K<sub>1</sub> is an essential cofactor for the\nposttranslational\nmodification of Vitamin K<sub>1</sub>-dependent proteins, regulating\nblood coagulation, bone mineralization, and anti-inflammatory processes.\nIts bile-dependent bioavailability points toward the importance of\nunderstanding its largely unknown interplay with bile. We detailed\nthe interaction of Vitamin K<sub>1</sub> with bile using simulating\nintestinal fluids and studied the effects of bile on Vitamin K<sub>1</sub> solubilization and permeation across artificial membranes.\nOur results indicate that transitioning from fasted to the fed-state\nbile concentrations critically impacted Vitamin K<sub>1</sub> performances.\nIn the fasted state, flux inversely correlated with the bile concentrations.\nStarting at the fasted-to-fed transition, this flipped, and Vitamin\nK<sub>1</sub> solubility increased 8-fold, while the flux increased\nup to 5-fold. When fed, Vitamin K<sub>1</sub> was mainly present in\nsmall colloidal species, maintaining Vitamin K<sub>1</sub> solubility\nand rapid exchange dynamics with the surrounding fluids. In conclusion,\na fed state is a critical prerequisite for effective Vitamin K<sub>1</sub> solubilization and molecular presentation within the gastrointestinal\ntract. Analogous studies with Vitamin D<sub>3</sub>, another lipophilic\nvitamin, provided evidence that the mechanism of bile interaction\nnow detailed for Vitamin K<sub>1</sub> is not conserved across different\nvitamins. These outcomes detail Nature’s strategy for the nutritional\nexploitation of Vitamin K<sub>1</sub> by bile, with immediate relevance\nfor diet plans and future nutraceutical designs.