Effects of Vitamin D2 Supplementation on Vitamin D3 Metabolism in Health and CKD

Background and objectives Vitamin D supplements are prescribed to correct low circulating concentrations of 25-hydroxyvitamin D. In CKD, vitamin D metabolism is complicated by decreased conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D by CYP27B1 and possibly decreased conversion of 25-hydroxyvitamin D to 24,25-dihydroxyvitamin D by CYP24A1. The aim of this study was to determine the effects of vitamin D-2 supplementation on vitamin D metabolism in health and CKD. Design, setting, participants, & measurements We conducted a treatment-only intervention study of 25 individuals with CKD (eGFR<60 ml/ min per 1.73 m(2)) and 44 individuals without CKD from three academic centers, all with screening 25-hydroxyvitamin D <30 ng/ ml. Each participant was prescribed vitamin D-2 (ergocalciferol) 50,000 IU orally twice weekly for 5 weeks. We tested whether changes in plasma concentrations of vitamin D metabolites and vitamin D metabolic ratios differed by CKD status. Plasma 1,25-dihydroxyvitamin D-3-to-25-hydroxyvitamin D(3)Z ratio and 24,25-dihydroxyvitamin D-3-to-25-hydroxyvitamin D-3 ratio were calculated as estimates of CYP27B1 and CYP24A1 function, respectively. Results With treatment, plasma 25-hydroxyvitamin D-2 and total 25-hydroxyvitamin D concentrations increased similarly for participants with and without CKD. For participants without CKD, 1,25-dihydroxyvitamin D-2 increased (2.8 +/- 1.3-32.9 +/- 1.4 pg/ ml), whereas 1,25-dihydroxyvitamin D-3 decreased (45.6 +/- 1.9-14.6 +/- 1.9 pg/ ml), resulting in no significant change in total 1,25-dihydroxyvitamin D; 1,25-dihydroxyvitamin D-3-to-25-hydroxyvitamin D-3 ratio decreased (3.0 +/- 0.2-1.7 +/- 0.2 pg/ng), and 24,25-dihydroxyvitamin D-3-to-25-hydroxyvitamin D-3 ratio increased (115.7 +/- 7.8-195.2 +/- 7.9 pg/ng). Individuals with CKD had lower baseline levels and smaller changes in magnitude for 1,25-dihydroxyvitamin D-2 (2.1 +/- 1.6-24.4 +/- 1.6 pg/ml; P interaction =0.01), 1,25-dihydroxyvitamin D-3-to-25-hydroxyvitamin D-3 ratio (1.8 +/- 0.2-1.1 +/- 0.2 pg/ng; P interaction =0.05), and 24,25-dihydroxyvitamin D-3-to-25-hydroxyvitamin D-3 ratio (72.0 +/- 9.1-110.3 +/- 9.3 pg/ng; P interaction <0.001). Fibroblast growth factor -23 and parathyroid hormone were not significantly changed in either group. Conclusions Vitamin D-2 supplementation decreases conversion of 25-hydroxyvitamin D-3 to 1,25-dihydroxyvitamin D-3 and induces vitamin D-3 catabolism as evidenced by changes in D-3 metabolites and vitamin D metabolic ratios. These effects occur without significant changes in fibroblast growth factor -23 or parathyroid hormone and are blunted in CKD.