A randomized trial of vitamin D₃ supplementation 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.

Figure 1.

A, Study design. B, Participants recruited and retained.

Figure 2.

Change in serum 25(OH)D after 12 weeks of D3 supplementation (n = 323). In the schematic box plots, diamonds indicate means, horizontal lines indicate medians, shaded boxes indicate interquartile ranges (IQR), whiskers indicate highest value below the upper fence (1.5 × IQR above the 75th percentile) and the lowest value above the lower fence (1.5 × IQR below the 25th percentile), and circles indicate values outside the upper and lower fences. For vitamin D dose, P < .0001 for trend.

Figure 3.

A, Fitted 25(OH)D curves over time for the overall sample (n = 323). B, Fitted 1,25(OH)₂D curves over time for the overall sample (n = 323). The majority of subjects completed the study within 12 weeks; however, data were included from several subjects who were enrolled up to 65 days after the 12-week intervention.

Figure 4.

A–C, Relationship between serum 25(OH)D and fractional calcium absorption at baseline (A) (serum 25(OH)D, P = .001; race [white vs black], P < .0001; slope = −0.002, R² = 0.073, n = 297); 12 weeks (B) (25(OH)D, P = .13; race (white vs black), P < .0001; R² = 0.071, n = 297) and (C) as change from baseline to 12 weeks (C) (25(OH)D, P = .66; race, P = .12; R² = 0.013, n = 297). D, Relationship between vitamin D dose and change in fractional calcium absorption after 12 weeks of supplementation (vitamin D dose, P = .54; race, P = .12). Filled circles and solid lines indicate blacks, and open circles and dotted lines indicate whites.