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

Vitamin D₃ 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 D₃ can also be obtained from oral sources. However, the actual biological equivalence of naturally produced (i.e., UVB-irradiation of skin) and oral vitamin D₃  has not been determined. We previously identified a unique and specific transport mechanism for skin-generated vitamin D₃ which requires vitamin D binding protein (DBP); a mechanism that differs from absorption and transport of oral vitamin D₃ . In the following report, we examined the impact of this difference on the biological activity of vitamin D₃ . We report that UVB-generated vitamin D₃ is more potent at raising serum calcium compared to oral vitamin D₃ , with the total biological activity being twofold higher. By examining the excretion of radiolabeled vitamin D₃ injected unbound or pre-bound by DBP, we attributed the increased activity of skin-generated vitamin D₃ to a significant reduction in biliary excretion of DBP-bound vitamin D relative to unbound vitamin D. Thus, removal of vitamin D₃ from the skin by the natural DBP system markedly improves biological activity compared to that given orally.