High-dose vitamin D-3 reduces circulating hepcidin concentrations: A pilot, randomized, double-blind, placebo-controlled trial in healthy adults

• Type of Material: Article
• Authors: Ellen M. Smith, Emory University; Jessica A. Alvarez, Emory University; Malcolm D. Kearns, Emory University; Li Hao, Emory University; John H. Sloan, Eli Lilly and Company; Robert J. Konrad, Eli Lilly and Company; Thomas R Ziegler, Emory University; Susu M Zughaier, Emory University; Vin Tangpricha, Emory University
• Language: English
• Date: 2017-08-01
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016 Published by Elsevier Ltd.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.clnu.2016.06.015
• Title of Journal or Parent Work: Clinical Nutrition
• ISSN: 0261-5614
• Volume: 36
• Issue: 4
• Start Page: 980
• End Page: 985
• Grant/Funding Information: This work was supported, in part, by National Institutes of Health grants T32 DK007734 (EMS), K01 DK102851 (JAA), K24 DK096574 (TRZ), and UL1 TR000454 (Atlanta Clinical and Translational Science Institute).
• Keywords: HYPOVITAMINOSIS D; UNITED-STATES; Hepcidin; Iron; NUTRITION EXAMINATION SURVEY; Nutrition & Dietetics; METABOLISM; IRON-DEFICIENCY ANEMIA; NATIONAL-HEALTH; PREVALENCE; Science & Technology; Vitamin D; HEMODIALYSIS-PATIENTS; Life Sciences & Biomedicine; Anemia; ERYTHROPOIETIN; Inflammation; IMPROVES ANEMIA
• Research Categories: Biology, Microbiology; Health Sciences, Nutrition

Abstract

Background & aims In vitro studies suggest that vitamin D may reduce hepcidin expression and pro-inflammatory cytokine release from monocytes. However, data assessing the vitamin D-mediated effects on iron recycling in healthy individuals are lacking. We aimed to examine the effect of high-dose vitamin D3on plasma hepcidin, inflammatory cytokine, and ferritin concentrations in healthy adults. Methods This was a pilot, double-blind, placebo-controlled trial in healthy adults (N = 28) randomized to receive a one-time oral dose of 250,000 IU of vitamin D3or placebo. Between- and within-group differences in plasma hepcidin, pro-inflammatory cytokine [interleukin (IL)-1β, IL-6, IL-8, monocyte chemoattractant protein-1 (MCP-1)], and ferritin concentrations at baseline and 1 week were determined using two-sample and paired t-tests, respectively. Results At baseline, plasma 25-hydroxyvitamin D [25(OH)D], hepcidin, pro-inflammatory cytokine, and ferritin concentrations did not differ between the two groups, and greater than 70% of subjects in both groups were vitamin D deficient (25(OH)D < 20 ng/mL). After 1 week, plasma hepcidin concentrations decreased by 73% from baseline in those who received vitamin D3(geometric mean ratio [GMR] = 0.27 (95% CI: 0.11–0.62); P = 0.005); there was no significant change in the placebo group (GMR = 0.73 (95% CI: 0.49–1.09); P = 0.11). Plasma cytokine and ferritin concentrations did not change significantly in either group. Conclusions High-dose vitamin D3significantly reduced plasma hepcidin concentrations in healthy adults 1 week post-dosing, without a change in plasma pro-inflammatory cytokine or ferritin concentrations. These data suggest that vitamin D may have a role in regulating iron recycling by acting independently of changes in pro-inflammatory markers.