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Effects of Vitamin D2 Supplementation on Vitamin D3 Metabolism in Health and CKD.
Clin J Am Soc Nephrol. 2017 Sep 07; 12(9):1498-1506.CJ

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.

Authors+Show Affiliations

Divisions of Metabolism, Endocrinology and Nutrition and Batacchi@uw.edu. Kidney Research Institute, and.Kidney Research Institute, and. Nephrology.Divisions of Metabolism, Endocrinology and Nutrition and. Kidney Research Institute, and. Department of Laboratory Medicine, University of Washington, Seattle, Washington.Division of Nephrology and Hypertension, Department of Medicine and. Center for Translational Metabolism and Health, Northwestern University Feinberg School of Medicine, Chicago, Illinois.Kidney Research Institute, and. Nephrology.Division of Nephrology, St. Louis University, St. Louis, Missouri.Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina; and.Kidney Research Institute, and. Nephrology. Veterans Affairs Puget Sound Health Care System, Seattle, Washington.

Pub Type(s)

Journal Article
Multicenter Study

Language

eng

PubMed ID

28768705

Citation

Batacchi, Zona, et al. "Effects of Vitamin D2 Supplementation On Vitamin D3 Metabolism in Health and CKD." Clinical Journal of the American Society of Nephrology : CJASN, vol. 12, no. 9, 2017, pp. 1498-1506.
Batacchi Z, Robinson-Cohen C, Hoofnagle AN, et al. Effects of Vitamin D2 Supplementation on Vitamin D3 Metabolism in Health and CKD. Clin J Am Soc Nephrol. 2017;12(9):1498-1506.
Batacchi, Z., Robinson-Cohen, C., Hoofnagle, A. N., Isakova, T., Kestenbaum, B., Martin, K. J., Wolf, M. S., & de Boer, I. H. (2017). Effects of Vitamin D2 Supplementation on Vitamin D3 Metabolism in Health and CKD. Clinical Journal of the American Society of Nephrology : CJASN, 12(9), 1498-1506. https://doi.org/10.2215/CJN.00530117
Batacchi Z, et al. Effects of Vitamin D2 Supplementation On Vitamin D3 Metabolism in Health and CKD. Clin J Am Soc Nephrol. 2017 Sep 7;12(9):1498-1506. PubMed PMID: 28768705.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of Vitamin D2 Supplementation on Vitamin D3 Metabolism in Health and CKD. AU - Batacchi,Zona, AU - Robinson-Cohen,Cassianne, AU - Hoofnagle,Andrew N, AU - Isakova,Tamara, AU - Kestenbaum,Bryan, AU - Martin,Kevin J, AU - Wolf,Myles S, AU - de Boer,Ian H, Y1 - 2017/08/02/ PY - 2017/01/15/received PY - 2017/05/25/accepted PY - 2017/8/5/pubmed PY - 2018/5/22/medline PY - 2017/8/4/entrez KW - Vitamin D KW - chronic kidney disease KW - metabolism SP - 1498 EP - 1506 JF - Clinical journal of the American Society of Nephrology : CJASN JO - Clin J Am Soc Nephrol VL - 12 IS - 9 N2 - 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. SN - 1555-905X UR - https://www.unboundmedicine.com/medline/citation/28768705/Effects_of_Vitamin_D2_Supplementation_on_Vitamin_D3_Metabolism_in_Health_and_CKD_ L2 - https://cjasn.asnjournals.org/cgi/pmidlookup?view=long&amp;pmid=28768705 DB - PRIME DP - Unbound Medicine ER -