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

Richard D Lewis, E M Laing, K M Hill Gallant, Daniel B Hall, G P McCabe, D B Hausman, B R Martin, S J Warden, Munro Peacock, C M Weaver

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)4816-25
Number of pages10
JournalThe Journal of clinical endocrinology and metabolism
Issue number12
StatePublished - Dec 2013


  • Adolescent
  • African Americans
  • Calcifediol/blood
  • Calcitriol/blood
  • Calcium, Dietary/metabolism
  • Child
  • Child Development
  • Cholecalciferol/administration & dosage
  • Dietary Supplements/adverse effects
  • Double-Blind Method
  • European Continental Ancestry Group
  • Female
  • Georgia
  • Humans
  • Indiana
  • Intestinal Absorption/ethnology
  • Male
  • Models, Biological
  • Parathyroid Hormone/blood
  • Seasons
  • Sunlight
  • Vitamin D Deficiency/blood

PubMed: MeSH publication types

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

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