Effects of vitamin D₂ supplementation on vitamin D₃ metabolism in health and CKD

Background and objectives VitaminDsupplements are prescribed to correct lowcirculating concentrations of 25-hydroxyvitaminD. InCKD, vitaminDmetabolismis 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 D₂ supplementation on vitamin D metabolism in health and CKD. Design, setting, participants, &measurementsWeconducteda treatment-only interventionstudy of 25 individuals with CKD(eGFR, 60 ml/min per 1.73m²) and 44 individualswithout CKDfromthree academic centers, allwith screening 25-hydroxyvitaminD, 30 ng/ml. Each participantwas prescribedvitamin D₂ (ergocalciferol) 50, 000 IU orally twice weekly for 5 weeks.We tested whether changes in plasma concentrations of vitamin D metabolites and vitaminDmetabolic ratios differed by CKDstatus. Plasma 1, 25-dihydroxyvitamin D₃-to-25-hydroxyvitamin D₃ ratio an D₂4, 25-dihydroxyvitamin D₃-to-25-hydroxyvitamin D₃ ratiowere calculatedas estimates ofCYP27B1 and CYP24A1 function, respectively. Results With treatment, plasma 25-hydroxyvitamin D₂ and total 25-hydroxyvitamin D concentrations increased similarly for participants with and without CKD. For participants without CKD, 1, 25-dihydroxyvitamin D₂ increased (2.8±1.3–32.9±1.4 pg/ml), whereas 1, 25-dihydroxyvitamin D₃ 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 D₃-to-25-hydroxyvitamin D₃ ratiodecreased (3.0±0.2–1.7±0.2pg/ng), an D₂4, 25-dihydroxyvitamin D₃-to-25-hydroxyvitamin D₃ 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 D₂ (2.1±1.6–24.4±1.6 pg/ml; P interaction =0.01), 1, 25-dihydroxyvitamin D₃-to-25-hydroxyvitamin D₃ ratio (1.8±0.2–1.1±0.2 pg/ng; P interaction =0.05), and 24, 25-dihydroxyvitamin D₃-to-25-hydroxyvitamin D₃ 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 D₂ supplementation decreases conversion of 25-hydroxyvitamin D₃ to 1, 25-dihydroxyvitamin D₃ and induces vitamin D₃ catabolismas evidenced by changes in D₃ metabolites and vitamin Dmetabolic ratios. These effects occur without significant changes in fibroblast growth factor-23 or parathyroid hormone and are blunted in CKD.