Vitamin D binding protein greatly improves bioactivity but is not essential for orally administered vitamin D

Vitamin D 3 is a prohormone that is essential for calcium homeostasis. It is naturally produced in the skin by ultraviolet‐B (UVB) irradiation of 7‐dehydrocholesterol. In the absence of skin production, vitamin D 3 can also be obtained from oral sources. However, the actual biological equivalence of naturally produced (i.e., UVB‐irradiation of skin) and oral vitamin D 3  has not been determined. We previously identified a unique and specific transport mechanism for skin‐generated vitamin D 3 which requires vitamin D binding protein (DBP); a mechanism that differs from absorption and transport of oral vitamin D 3 . In the following report, we examined the impact of this difference on the biological activity of vitamin D 3 . We report that UVB‐generated vitamin D 3 is more potent at raising serum calcium compared to oral vitamin D 3 , with the total biological activity being twofold higher. By examining the excretion of radiolabeled vitamin D 3 injected unbound or pre‐bound by DBP, we attributed the increased activity of skin‐generated vitamin D 3 to a significant reduction in biliary excretion of DBP‐bound vitamin D relative to unbound vitamin D. Thus, removal of vitamin D 3 from the skin by the natural DBP system markedly improves biological activity compared to that given orally.