The effect of a single, large bolus of vitamin D in healthy adults over the winter and following year: a randomized, double-blind, placebo-controlled trial

Abstract

Background/objectives: Although single, high doses of vitamin D effectively maintain vitamin D sufficiency in several populations, no studies have evaluated healthy adults over winter, during which vitamin D status declines. This study investigated whether high-dose vitamin D3 given once to healthy adults before winter will (1) prevent the wintertime decline in vitamin D status, (2) promote vitamin D sufficiency 1 year following the dose and (3) prevent the rise of parathyroid hormone (PTH) concentrations.

Subjects/methods: In this double-blind, placebo-controlled trial, we assessed plasma 25(OH)D and PTH concentrations at baseline, 5, 90 and 365 days after drug administration in 28 healthy adults. In all, >80% of subjects returned at each time point.

Results: At baseline, the young, healthy participants had a mean plasma 25(OH)D concentration of 17.5±6.1 ng/ml. Only two subjects exhibited plasma 25(OH)D concentrations >30 ng/ml. At 5 days, subjects randomized to vitamin D3 had a higher mean plasma 25(OH)D concentration compared with the placebo group (39.1 vs 19.1 ng/ml, P<0.001). Plasma 25(OH)D concentrations returned to baseline at 90 and 365 days in the vitamin D3 group and remained unchanged in the placebo group. PTH and calcium concentrations were unrelated to changes in 25(OH)D levels and similar between groups over time.

Conclusions: A dose of 250,000 IU of vitamin D3 given once in November resulted in a robust increase in plasma 25(OH)D after 5 days, but it was unable to sustain this increase after 90 days. A larger or more frequent dosing regimen may be needed for long-term vitamin D sufficiency.

Trial registration: ClinicalTrials.gov NCT01924910.

Figure 1

CONSORT Diagram. Twenty-nine adults were deemed eligible for inclusion by our screening questionnaire and provided informed consent for participation in the study. One subject declined participation following consent and before administration of the vitamin D dose or placebo. The remaining 28 subjects were randomized into blocks of six. In each block, three subjects received placebo and three received vitamin D. The subjects demonstrated good follow-up (>80% at 5, 90 and 365 days) with attrition randomly in both groups, aside from one subject who did not return following the dose in the placebo group.

Figure 2

Geometric mean plasma 25(OH)D at each visit. Plasma 25-hydroxyvitamin D (25(OH)D) concentrations were measured at baseline, 5 days, 90 days and 365 days following an oral dose of 250 000 IU of vitamin D₃. The plasma 25(OH)D concentration increased 130% relative to placebo at the 5-day time point (GMR 2.31, P<0.0001), but it did not sustain this significant increase at additional time points. There was no significant change in either group from baseline measured over the winter months (comparing baseline and 90-day time points). Geometric means at each visit are plotted, together with their 95% confidence intervals.

Figure 3

Geometric mean plasma PTH at each visit. Plasma parathyroid hormone (PTH) concentrations were measured at baseline, 5 days, 90 days and 365 days following an oral dose of 250 000 IU vitamin D₃. At baseline, no participants had abnormal PTH concentrations. There was no significant difference between PTH concentrations at baseline and any additional time points or between groups. Geometric means at each visit are plotted, together with their 95% confidence intervals.