Short-Term Effects of Escalating Doses of Cholecalciferol on FGF23 and 24,25(OH)2 Vitamin D Levels: A Preliminary Investigation

Background: There are few and controversial results on 24,25(OH)(2)D and FGF23 acute changes following supplementation with cholecalciferol. Methods: Twenty-seven subjects with 25(OH)D < 30 ng/mL were randomized into three groups to receive a single oral dose of 25,000 I.U. or 600,000 I.U. of cholecalciferol or placebo, respectively. We measured 25(OH)D, 1,25(OH)(2)D, 24,25(OH)(2)D, and FGF23 levels at baseline and after 72 h. The 1,25(OH)(2)D/25(OH)D, 1,25(OH)(2)D/24,25(OH)2D, and 24,25(OH)2D/25(OH)D ratios were also calculated. Results: There was an increase in 25(OH)D and 1,25 (OH)(2)D following both doses of cholecalciferol. In the group administered 600,000 I.U., there was a significant increase in the delta changes in 25(OH)D and 1,25(OH)(2)D compared to the placebo and in the delta 24,25(OH)D2 compared to the placebo and 25,000 I.U. groups (all p < 0.05). A decrease in both the 1,25(OH)2D/25(OH)D and 1,25(OH)2D/24,25(OH)2D ratio (all p < 0.05) was observed in the 600,000 I.U. group. FGF23 values significantly increased only in the group administered 600,000 I.U. Conclusions: 25(OH)D and 1,25(OH)D levels significantly increased following 600,000 IU cholecalciferol administration compared to 25,000 I.U. and placebo. Following the massive administration of cholecalciferol, the CYP24A1 enzyme is actively involved in catabolism, thus, avoiding toxic effects.