Short- and long-term safety of weekly high-dose vitamin D3 supplementation in school children

Abstract

Background: Hypovitaminosis D is prevalent in youth worldwide, but the safety of vitamin D at doses exceeding 200 IU/d is unknown in this age group. We assessed the safety of high doses of vitamin D(3) administered to apparently healthy schoolchildren.

Methods: To assess short-term safety, 25 subjects randomly received placebo or vitamin D(3) at doses of 14,000 IU/wk for 8 wk. To assess long-term safety, 340 subjects randomly received placebo, vitamin D(3) as 1,400 IU/wk or 14,000 IU/wk for 1 yr. Biochemical variables were monitored at 0, 2, 4, 6, and 8 wk and 8 wk off therapy in the short-term study and at 0, 6, and 12 months in the long-term study.

Results: In both the short- and long-term studies, mean serum calcium and 1,25-hydroxyvitamin levels did not change in any group. In the short-term study, mean 25-hydroxyvitamin concentrations increased from 44 (+/- 11) to 54 (+/- 19) ng/ml in the treated groups (P = 0.033). In the long-term study, mean 25-hydroxyvitamin D levels increased from 15 +/- 8 to 19 +/- 7 ng/ml (P < 0.0001) in subjects receiving 1,400 IU/wk and from 15 +/- 7 to 36 +/- 22 ng/ml (P < 0.0001) in the group receiving 14,000 IU/wk. No subject developed vitamin D intoxication.

Conclusion: Vitamin D(3) at doses equivalent to 2000 IU/d for 1 yr is safe in adolescents and results in desirable vitamin D levels.

Figure 1

Serum 25-OHD (A) and calcium (B) at 0, 2, 4, 6, and 8 wk (August to October) and 8 wk off therapy (December) in the short-term study, by treatment group. The box plot shows the median (50th percentile) as a line and the first (25th percentile) and third quartile (75th percentile) of the distribution as the lower and upper parts of the box. The whiskers shown above and below the boxes represent the largest and smallest observed values that are less than 1.5 box lengths from the end of the box. Analyses conducted using repeated-measures ANOVA. In the Sigma group, mean 25-OHD was 49 ± 12 ng/ml at baseline, 53 ± 19 ng/ml (P = 0.440) after 8 wk of supplementation and decreased to 38 ± 10 ng/ml at 2 wk off therapy (P = 0.01 vs. the 8 wk value). In the Vigantol group, mean 25-OHD concentration group increased from 37 ± 6 ng/ml at baseline to 54 ± 20 ng/ml (P = 0.043) after 8 wk of supplementation and then decreased to 33 ± 7 ng/ml at 2 wk off therapy (P = 0.018 compared with the 8 wk value). *, No significant difference in 25-OHD levels between D₃ groups at similar time points; †, 25-OHD levels were significantly higher in D₃ group(s), compared with the placebo group, at 8 wk and 8 wk off therapy (P < 0.05). There were no significant differences in serum calcium levels achieved at 8 wk and 8 wk off therapy among the three groups (ANOVA). Biochemical assays are reported in metric units. To convert from metric to SI units, multiply calcium by 0.25 (millimoles per liter); 25-OHD by 2.496 (nanomoles per liter).

Figure 2

Effect of vitamin D₃ supplementation on serum calcium, 25-OHD, and 1,25-OHD in the short-term study, by treatment group. Individual values for serum calcium, 25-OHD, and 1,25-OHD at baseline and 8 wk for the 25 subjects are shown. Biochemical assays are reported in metric units. To convert from metric to SI units, multiply calcium by 0.25 (millimoles per liter); 25-OHD by 2.496 (nanomoles per liter); 1,25-OHD by 2.6 (picomoles per liter).

Figure 3

Effect of Vitamin D3 supplementation on serum calcium (A), 25-OHD (B), and 1,25-OHD (C) in girls (A) and boys (B), in the long-term study, by treatment group. Low-dose group received 1,400 IU D₃ per week and high-dose group 14,000 IU D₃ per week. The box plot shows the median (50th percentile) as a line and the first (25th percentile) and third quartile (75th percentile) of the distribution as the lower and upper parts of the box. The whiskers shown above and below the boxes represent the largest and smallest observed values that are less than 1.5 box lengths from the end of the box. *, P < 0.05 in mean value of corresponding variable between 0 and 12 months within a treatment group; †, P < 0.0001 in mean value of corresponding variable at 12 months in the high-dose group, compared with both the low-dose and placebo groups. Biochemical assays are reported in metric units. To convert from metric to SI units, multiply calcium by 0.25 (millimoles per liter); 25-OHD by 2.496 (nanomoles per liter); 1,25-OHD by 2.6 (picomoles per liter).