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

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.gov NCT01240265) in 40 lactating women. Interventions: Subjects were randomized to receive vitamin D₃ orally, either a single dose of 150,000 IU or 5000 IU daily for 28 days. Vitamin D metabolites were measured in serum and breast milk at baseline, 1, 3, 7, 14 and 28 days. 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 28 days, 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 28 days and were greater than the daily dose group at 14 and 28 days (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 28 days 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.