Abstract
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.govNCT01240265) in 40 lactating women. INTERVENTIONS: Subjects were randomized to receive vitamin D(3) 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)(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 28days, 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 28days and were greater than the daily dose group at 14 and 28days (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 D(3) 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 28days 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.