A randomized trial of vitamin D₃ supplementation in children: dose-response effects on vitamin D metabolites and calcium absorption

J Clin Endocrinol Metab. 2013 Dec;98(12):4816-25. doi: 10.1210/jc.2013-2728. Epub 2013 Oct 3.

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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Black or African American
  • Calcifediol / blood
  • Calcifediol / metabolism
  • Calcitriol / blood
  • Calcitriol / metabolism
  • Calcium, Dietary / metabolism*
  • Child
  • Child Development*
  • Cholecalciferol / administration & dosage*
  • Cholecalciferol / adverse effects
  • Cholecalciferol / metabolism
  • Cholecalciferol / therapeutic use
  • Dietary Supplements* / adverse effects
  • Double-Blind Method
  • Female
  • Georgia
  • Humans
  • Indiana
  • Intestinal Absorption* / ethnology
  • Male
  • Models, Biological*
  • Parathyroid Hormone / blood
  • Parathyroid Hormone / metabolism
  • Seasons
  • Sunlight
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / ethnology
  • Vitamin D Deficiency / metabolism
  • Vitamin D Deficiency / prevention & control*
  • White People

Substances

  • Calcium, Dietary
  • PTH protein, human
  • Parathyroid Hormone
  • Cholecalciferol
  • Calcitriol
  • Calcifediol