25-Hydroxylation of vitamin D3:: relation to circulating vitamin D3 under various input conditions

Background: Neither the efficiency of the 25-hydroxylation of vitamin D nor the steady state relation between vitamin D-3 and 25-hydroxyvitamin D [25(OH)D] has been studied in humans. Objective: We aimed to examine the relation between serum vitamin D-3 and 25(OH)D in normal subjects after either oral administration of vitamin D-3 or ultraviolet-B radiation across a broad range of inputs. Design: Values for serum vitamin D-3 and (OH)D-3 were aggregated from 6 studies-1 acute and 5 near-steady state-at various vitamin D-3 inputs. In 3 of the steady state studies, vitamin D-3 had been administered for 18-26 wk in doses of 0 to 11000 IU/d; in 2 studies, subjects had received solar or ultraviolet-B irradiation. Results: In the acute study, subjects receiving a single 100 000-IU dose of vitamin D-3 had arise in serum cholecalciferol to a mean of 521 nmol/L at 1 d and then a fall to near-baseline values by 7-14 d. Serum 25(OH)D peaked at 103 nmol/L on day 7 and fell slowly to baseline by day 112. In the 5 steady state studies, the relation of serum 25(OH)D to serum vitamin D-3 was biphasic and was well described by a combined exponential and linear function: Y = 0.433X + 87.81 [1-exp (-0.468X)], with R-2 = 0.448. Conclusions: At physiologic inputs, there is rapid conversion of precursor to product at low vitamin D-3 concentrations and a much slower rate of conversion at higher concentrations. These data suggest that, at typical vitamin D-3 inputs and serum concentrations, there is very little native cholecalciferol in the body, and 25(OH)D constitutes the bulk of vitamin D reserves. However, at supraphysiologic inputs, large quantities of vitamin D-3 are stored as the native compound, presumably in body fat, and are slowly released to be converted to 25(OH)D.