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

Abstract

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 D₂ 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 m²) and 44 individuals without CKD from three academic centers, all with screening 25-hydroxyvitamin D <30 ng/ml. Each participant was prescribed vitamin D₂ (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 D₃-to-25-hydroxyvitamin D₃ ratio and 24,25-dihydroxyvitamin D₃-to-25-hydroxyvitamin D₃ ratio were calculated as estimates of CYP27B1 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 ratio decreased (3.0±0.2-1.7±0.2 pg/ng), and 24,25-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 catabolism as evidenced by changes in D₃ 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.

Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2017_08_02_CJASNPodcast_17_09.mp3.

Keywords: Vitamin D; chronic kidney disease; metabolism.