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 D-3 can adequately meet vitamin D requirements of the breastfed infant. We compared the effect of bolus versus daily vitamin D-3 dosing in lactating mothers on vitamin D-3 catabolism. We hypothesized that catabolism of 25(OH)D-3 to 24,25(OH)(2)D-3 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)(2)D-3/25(OH)D-3 ratio. Results: The concentration of serum 24,25(OH)(2)D-3 was directly related to that of 25(OH)D in both groups (r(2) = 0.63; p < 0.001). The mean (+/- SD) 24,25(OH)(2)D-3/25(OH)D-3 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)(2)D-3 lagged behind that of 25(OH)D, but the 24,25(OH)(2)D-3/25(OH)D-3 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)(2)D-3/25(OH)D-3 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)(2)D-3/25(OH)D-3 ratio (r(2) = 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)(2)D-3, presumably via induction of the 24-hydroxylase enzyme (CYP24A1), relative to the 25(OH)D-3 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)D-3 with lesser diversion of 25(OH)D-3 to 24,25(OH)(2)D-3 than does larger bolus dosing. (C) 2018 Elsevier Inc. All rights reserved.