Effects of High Doses of Cholecalciferol in Normal Subjects: A Randomized Double-Blinded, Placebo-Controlled Trial

Randomized, double-blind, placebo-controlled trial in healthy vitamin D-insufficient adults aged 18 years or older at Roskilde University Hospital in Denmark. The active cholecalciferol group had 22 participants who completed treatment; overall, 50 participants were randomized and 40 completed the study.

The active arm received oral cholecalciferol 3000 IU daily, given as 3 tablets of vitamin D3, for 16 weeks. The regimen was compared with placebo.

Cholecalciferol did not significantly change 24-hour urinary calcium excretion versus placebo, but it substantially increased circulating vitamin D metabolites. The primary endpoint, change in 24-hour urinary calcium excretion, showed no between-group difference (P = 0.891). In the active group, 25(OH) vitamin D increased 186% versus 14% in placebo (P < 0.001) and 1,25(OH)2 vitamin D increased 28% versus -8% in placebo (P < 0.001). FGF23 increased 10% in the cholecalciferol group (P = 0.018), but the between-group difference in FGF23 change was not significant (P = 0.457). The authors concluded that high-dose cholecalciferol increased vitamin D metabolites without major changes in mineral metabolism, although some individuals may be sensitive to a calciuric effect.

Small sample size, with only 22 participants in the active arm and 16-week follow-up, limits precision and long-term interpretation. The study was restricted to healthy, predominantly Caucasian vitamin D-insufficient adults in Denmark, which limits generalizability. Attrition occurred, and the trial may not detect rare or individual-level calciuric responses despite a null group-level result.