A Randomized Trial of Vitamin D₃Supplementation in Children: Dose-Response Effects on Vitamin D Metabolites and Calcium Absorption

Abstract

Context:Changes in serum vitamin D metabolites and calcium absorption with varying doses of oral vitamin D3 in healthy children are unknown.Objective:Our objective was to examine the dose-response effects of supplemental vitamin D3 on serum vitamin D metabolites and calcium absorption in children living at two U.S. latitudes.Design:Black and white children (n = 323) participated in a multisite (U.S. latitudes 34° N and 40° N), triple-masked trial. Children were randomized to receive oral vitamin D3 (0, 400, 1000, 2000, and 4000 IU/d) and were sampled over 12 weeks in winter. Serum 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured using RIA and intact PTH (iPTH) by immunoradiometric assay. Fractional calcium absorption was determined from an oral stable isotope 44Ca (5 mg) in a 150-mg calcium meal. Nonlinear and linear regression models were fit for vitamin D metabolites, iPTH, and calcium absorption.Results:The mean baseline 25(OH)D value for the entire sample was 70.0 nmol/L. Increases in 25(OH)D depended on dose with 12-week changes ranging from −10 nmol/L for placebo to 76 nmol/L for 4000 IU. Larger 25(OH)D gains were observed for whites vs blacks at the highest dose (P < .01). Gains for 1,25(OH)2D were not significant (P = .07), and decreases in iPTH were not dose-dependent. There was no dose effect of vitamin D on fractional calcium absorption when adjusted for pill compliance, race, sex, or baseline 25(OH)D.Conclusion:Large increases in serum 25(OH)D with vitamin D3 supplementation did not increase calcium absorption in healthy children living at 2 different latitudes. Supplementation with 400 IU/d was sufficient to maintain wintertime 25(OH)D concentrations in healthy black, but not white, children.

Effect of high-dose vitamin D supplementation on bone density in youth with osteogenesis imperfecta: A randomized controlled trial

“…On average, supplementation with high-doses of vitamin D (2000 IU) in healthy children has resulted in increments of serum 25OHD concentrations ranging from 37 to 52 nmol/L [146,167].…”

Treatment of Vitamin D Deficiency in Predominantly Hispanic and Black Adolescents: A Randomized Clinical Trial

“…17 In these guidelines, the Endocrine Society acknowledges that clinical trials are needed to better inform these recommendations across age and weight groups. Indeed, there are few randomized trials of vitamin D supplementation in adolescents 23–25 and even fewer trials of treatment of vitamin D deficiency in U.S. adolescents. 26, 27 These trials find dose-dependent and duration of treatment-dependent responses when comparing doses ranging from 200–4,000IU/day for 4 weeks up to one year.…”

Effect of Vitamin D3Supplementation in Black and in White Children: A Randomized, Placebo-Controlled Trial

“…Hill et al (5) found no inflection point in the inverse association between 25(OH)D and PTH in a cross-sectional study of 7-to 18-year-old children. Although Maguire et al (6) demonstrated plateauing of PTH at a 25(OH)D concentration of 42.8 ng/mL in a cross-sectional study of 1-to 6-year-old children, vitamin D supplementation (0, 400, 1000, 2000, and 4000 IU/d for 12 wk) in 9-to 13-year-old children had no effect on PTH concentrations despite dose-dependent increases in 25(OH)D concentrations (7).…”