Evaluation of ergocalciferol or cholecalciferol dosing, 1,600 IU daily or 50,000 IU monthly in older adults

Abstract

Context: Whether ergocalciferol (D(2)) and cholecalciferol (D(3)) are equally effective to increase and maintain serum 25-hydroxyvitamin D [25(OH)D] concentration is controversial.

Objective: The aim of the study was to evaluate the effect of daily and once monthly dosing of D(2) or D(3) on circulating 25(OH)D and serum and urinary calcium.

Design, setting and participants: In a university clinical research setting, 64 community dwelling adults age 65+ were randomly assigned to receive daily (1,600 IU) or once-monthly (50,000 IU) D(2) or D(3) for 1 yr.

Main outcome measures: Serum 25(OH)D, serum calcium, and 24-h urinary calcium were measured at months 0, 1, 2, 3, 6, 9, and 12. Serum PTH, bone-specific alkaline phosphatase, and N-telopeptide were measured at months 0, 3, 6, and 12.

Results: Serum 25(OH)D was less than 30 ng/ml in 40% of subjects at baseline; after 12 months of vitamin D dosing, levels in 19% of subjects (n = 12, seven receiving daily doses and five monthly doses) remained low, despite compliance of more than 91%. D(2) dosing increased 25(OH)D(2) but produced a decline (P < 0.0001) in 25(OH)D(3). Substantial between-individual variation in 25(OH)D response was observed for both D(2) and D(3). The highest 25(OH)D observed was 72.5 ng/ml. Vitamin D administration did not alter serum calcium, PTH, bone-specific alkaline phosphatase, N-telopeptide, or 24-h urine calcium.

Conclusions: Overall, D(3) is slightly, but significantly, more effective than D(2) to increase serum 25(OH)D. One year of D(2) or D(3) dosing (1,600 IU daily or 50,000 IU monthly) does not produce toxicity, and 25(OH)D levels of less than 30 ng/ml persist in approximately 20% of individuals. Substantial between-individual response to administered vitamin D(2) or D(3) is observed.

Trial registration: ClinicalTrials.gov NCT00692120.

Fig. 1.

Effect of vitamin D₂ or D₃ on serum 25(OH)D. The main figure presents mean 25(OH)D levels (sem) at each follow-up visit; inset presents mean change from baseline (sem). After 12 months of supplementation, serum 25(OH)D increased numerically to a greater extent with D₃ than D₂ with daily (9.2 vs. 6.1 ng/ml; P = 0.05; A) and monthly (8.9 vs. 3.6 ng/ml; P = 0.11; B) dosing. When the daily and monthly dosing groups are combined, a greater increase (P = 0.01) in 25(OH)D was observed (C) with D₃ (9.1 ng/ml) than with D₂ (4.8 ng/ml).

Fig. 2.

Impact of monthly vitamin D dosing on 25(OH)D. Serum 25(OH)D increases promptly after 50,000 IU of either vitamin D₂ or D₃. This phenomenon is present not only after the first dose, but also after the third monthly dose with a quite comparable increase in mean 25(OH)D (A). As noted in panel B, the decline over 1 month is such that the serum 25(OH)D increased by only 1.4 ng/ml with vitamin D₂ and 2.2 ng/ml with vitamin D₃.

Fig. 3.

Between-individual variability with daily and monthly vitamin D dosing. Variable responses in serum 25(OH)D to vitamin D dosing either daily or once-monthly is apparent for both vitamin D₂ and D₃, as well as for daily and monthly dosing (A). That the increase in 25(OH)D is not dependent solely on the 25(OH)D concentration at baseline is illustrated in panel B. In A and B, Baseline 25(OH)D value is represented by the open symbol and the 12-month value by the closed symbol.

Fig. 4.

Effect of D₂ dosing on circulating 25(OH)D₃ concentration. Ergocalciferol dosing, whether daily or monthly, produced a significant decline of approximately 12 ng/ml in circulating 25(OH)D₃ concentration (P < 0.0001).

Fig. 5.

Absence of effect of vitamin D supplementation on urine calcium. Twenty-four-hour urinary calcium excretion was unchanged (P = 0.14) in all groups over the 12 months of study.