Dual-modulation of nutrient-transporter axis and functionalized carriers: A paradigm shift for precision oral vitamin D delivery

The transintestinal epithelial absorption of vitamin D is intricately regulated by specific transport protein networks. Emerging evidence from molecular nutrition research reveals that certain dietary nutrients can enhance intestinal vitamin D absorption through targeted modulation of lipid transport pathways. Despite significant advancements in vitamin D delivery systems demonstrating excellent intestinal mucoadhesion and in vitro bioaccessibility, their clinical translation remains limited by suboptimal in vivo bioavailability. To address this critical challenge, we propose an innovative synergistic nutrient absorption strategy that establishes precise coordination among three key elements: dietary nutrient composition, transport protein regulation, and intestinal absorption optimization. This comprehensive review systematically examines: (1) The molecular mechanisms governing transintestinal vitamin D transport and physiological modulation of protein-mediated absorption pathways; (2) The regulatory effects of dietary components on vitamin D absorption efficiency through protein pathway modulation, proposing a novel "nutrient-transporter-vitamin D axis" strategy integrating cutting-edge carrier technologies; (3) Future perspectives for developing functionalized vitamin D delivery systems. The proposed paradigm shift, combining nutrient-mediated transport enhancement with advanced carrier engineering, represents a transformative approach to overcome current limitations in oral vitamin D delivery. This dual-modulation strategy synergistically improves intestinal absorption and systemic bioavailability through simultaneous optimization of biological transport mechanisms and pharmaceutical delivery parameters, offering new possibilities for precision nutrition interventions.