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 100000-IU dose of vitamin D(3) had a rise 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.