Effects of high doses of cholecalciferol in normal subjects: a randomized double-blinded, placebo-controlled trial

Birgitte Nygaard, Niels Erik Frandsen, Lisbet Brandi, Knud Rasmussen, Ove Vyff Oestergaard, Lars Oedum, Hans Christian Hoeck, Ditte Hansen, Birgitte Nygaard, Niels Erik Frandsen, Lisbet Brandi, Knud Rasmussen, Ove Vyff Oestergaard, Lars Oedum, Hans Christian Hoeck, Ditte Hansen

Abstract

Background: Vitamin D repletion with high doses of vitamin D is often recommended to patients and healthy subjects. The safety, especially concerning changes in urinary calcium excretion is of great importance.

Methods: In a double-blinded, placebo-controlled study in 40 healthy volunteers, we examined the changes in mineral metabolism during supplementation with 3000 IU of oral cholecalciferol daily during 4 months.

Results: Both 25(OH)vitamin D and 1,25(OH)2vitamin D increased significantly in the active treated group as compared to the placebo group (186% versus 14% (P<0.001) and 28% versus -8% (P<0.001)). No change was observed in urinary calcium excretion in the active group compared to the placebo group (P = 0.891). Fibroblast growth factor 23 increased significantly by 10% (P<0.018) in the active group. However, there was no difference in changes in FGF23 between treatment groups (P = 0.457).

Conclusion: High dose cholecalciferol significantly increases 25(OH)vitamin D and 1,25(OH)2vitamin D levels compared to placebo. No changes in urinary calcium excretion or other measured components of the mineral metabolism were found between groups.

Trial registration: ClinicalTrials.gov NCT00952562.

Conflict of interest statement

Competing Interests: BN, NEF, LB, OVO, LO and KR have declared that no competing interests exist. HCH is employed in a private company engaged in the conduction of clinical drug development programs from Phase I to Phase IV without any personal interest in the drugs under development. HCH has no affiliation to the commercial funders of this research. DH has received funding for other research projects from Abbott Laboratories A/S. D3 Pharmacy delivered the medication with no effect on publication. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1. Flow diagram demonstrating participantś flow…
Figure 1. Flow diagram demonstrating participantś flow through the study.
Figure 2. 25(OH)vitamin D, urinary calcium excretion,…
Figure 2. 25(OH)vitamin D, urinary calcium excretion, 1,25(OH)2vitamin D, PTH, FGF23 and urinary phosphate excretion at baseline and after 16 weeks of treatment with cholecalciferol 3000 IU/day or placebo.
Urinary calcium excretion: The laboratory reference interval (2.5–8.1 mmol/24 hour) is illustrated with dotted lines.
Figure 3. Box plots demonstrating changes in…
Figure 3. Box plots demonstrating changes in 25(OH)vitamin D, 1,25(OH)2vitamin D and urinary calcium excretion in the cholecalciferol group and placebo group during 16 weeks of treatment with cholecalciferol 3000 IU/day or placebo.
Figure 4. Changes in 1,25(OH) 2 vitamin…
Figure 4. Changes in 1,25(OH)2vitamin D according to baseline level of 25(OH)vitamin D in the cholecalciferol group, the placebo group and both treatment groups.
Changes in 1,25(OH)2vitamin D are depending on the baseline level of 25(OH)vitamin D β = linear regression coefficient.

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