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.