Comparison of the effect of daily versus bolus dose maternal vitamin D3 supplementation on the 24,25-dihydroxyvitamin D3 to 25-hydroxyvitamin D3 ratio

Abstract

Objective: Supplementing lactating mothers with high doses of vitamin D₃ can adequately meet vitamin D requirements of the breastfed infant. We compared the effect of bolus versus daily vitamin D₃ dosing in lactating mothers on vitamin D₃ catabolism. We hypothesized that catabolism of 25(OH)D₃ to 24,25(OH)₂D₃ would be greater in the bolus than in the daily dose group.

Design, setting and patients: Randomized controlled trial (clinicaltrials.govNCT01240265) in 40 lactating women.

Interventions: Subjects were randomized to receive vitamin D₃ orally, either a single dose of 150,000IU or 5000IU daily for 28days. Vitamin D metabolites were measured in serum and breast milk at baseline, 1, 3, 7, 14 and 28days.

Main outcome measure: Temporal changes in the serum 24,25(OH)₂D₃/25(OH)D₃ ratio.

Results: The concentration of serum 24,25(OH)₂D₃ was directly related to that of 25(OH)D in both groups (r²=0.63; p<0.001). The mean (±SD) 24,25(OH)₂D₃/25(OH)D₃ ratio remained lower at all time points than baseline values in the daily dose group (0.093±0.024, 0.084±0.025, 0.083±0.024, 0.080±0.020, 0.081±0.023, 0.083±0.018 at baseline, 1, 3, 7, 14, and 28days, respectively). In the single dose group, the increase in 24,25(OH)₂D₃ lagged behind that of 25(OH)D, but the 24,25(OH)₂D₃/25(OH)D₃ values (0.098±0.032, 0.067±0.019, 0.081±0.017, 0.092±0.024, 0.103±0.020, 0.106±0.024, respectively) exceeded baseline values at 14 and 28days and were greater than the daily dose group at 14 and 28days (p=0.003). The 24,25(OH)₂D₃/25(OH)D₃ ratio remained in the normal range with both dosing regimens. Greater breast milk vitamin D₃ values in the single dose group were inversely associated with the 24,25(OH)₂D₃/25(OH)D₃ ratio (r²=0.14, p<0.001), but not with daily dosing.

Conclusions: After a 14-day lag, a single high dose of vitamin D led to greater production of 24,25(OH)₂D₃, presumably via induction of the 24-hydroxylase enzyme (CYP24A1), relative to the 25(OH)D₃ value than did daily vitamin D supplementation, and this effect persisted for at least 28days after vitamin D administration. A daily dose of vitamin D may have more lasting effectiveness in increasing 25(OH)D₃ with lesser diversion of 25(OH)D₃ to 24,25(OH)₂D₃ than does larger bolus dosing.

Keywords: Catabolism; LC-MS/MS; Lactation; Nutrition; Safety; Vitamin D metabolism.

Figure 1

Alterations in (a) serum concentration of 24,25(OH)₂D₃, (b) serum concentration of 25(OH)D₃, (c) ratio of 25(OH)D₃/24,25(OH)₂D₃, and (d) serum concentration of cholecalciferol in single dose (open circle) and daily dose (black triangles) groups. The error bars represent standard deviations. P values are for comparison of values in daily and single dosing groups at corresponding time points.

Figure 2

Correlations between serum concentration of (a) 25(OH)D₃ and 24,25(OH)D₃ (r²=0.63; p < 0.0001), (b) serum 24,25(OH)₂D₃/25(OH)D₃ and serum 25(OH)D₃ (p<0.001), (c) serum 24,25(OH)₂D/25(OH)D₃ and breast milk vitamin D₃ and (d) serum 24,25(OH)₂D and breast milk vitamin D₃ in single dose (open circle) and daily dose (black triangles) groups. The solid line represents the linear trend in the daily dose group and the dotted line the linear trend in single dose group.