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25-Hydroxylation of vitamin D₃: relation to circulating vitamin D₃ under various input conditions^1,2,3

¹ From the Osteoporosis Research Center, Creighton University, Omaha, NE (RPH and LAGA); the Departments of Pediatrics (BWH) and Medicine (JRS and NHB), Medical University of South Carolina, Charleston, SC; and the Department of Medicine, University of Wisconsin, Madison, WI (NB)

Background: Neither the efficiency of the 25-hydroxylation of vitamin D nor the steady state relation between vitamin D₃ and 25-hydroxyvitamin D [25(OH)D] has been studied in humans.

Objective: We aimed to examine the relation between serum vitamin D₃ and 25(OH)D in normal subjects after either oral administration of vitamin D₃ or ultraviolet-B radiation across a broad range of inputs.

Design: Values for serum vitamin D₃ and (OH)D₃ were aggregated from 6 studies—1 acute and 5 near-steady state—at various vitamin D₃ inputs. In 3 of the steady state studies, vitamin D₃ 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 D₃ 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 D₃ was biphasic and was well described by a combined exponential and linear function: Y = 0.433X + 87.81[1–exp (–0.468X)], with R² = 0.448.

Conclusions: At physiologic inputs, there is rapid conversion of precursor to product at low vitamin D₃ concentrations and a much slower rate of conversion at higher concentrations. These data suggest that, at typical vitamin D₃ 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 D₃ are stored as the native compound, presumably in body fat, and are slowly released to be converted to 25(OH)D.

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