title: High-dose vitamin D3reduces circulating hepcidin concentrations: A pilot, randomized, double-blind, placebo-controlled trial in healthy adults.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Nutrition and Health Sciences Program, Laney Graduate School, Emory University, Atlanta, GA 30322, USA.
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Smith
authors.affiliation: Nutrition and Health Sciences Program, Laney Graduate School, Emory University, Atlanta, GA 30322, USA; Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Alvarez
authors.affiliation: Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Malcolm D
authors.initials: MD
authors.lastname: Kearns
authors.affiliation: Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Hao
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Sloan
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Konrad
authors.affiliation: Nutrition and Health Sciences Program, Laney Graduate School, Emory University, Atlanta, GA 30322, USA; Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Ziegler
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA; Atlanta Veterans Administration Medical Center (VAMC), Decatur, GA 30033, USA.
authors.forename: Susu M
authors.initials: SM
authors.lastname: Zughaier
authors.affiliation: Nutrition and Health Sciences Program, Laney Graduate School, Emory University, Atlanta, GA 30322, USA; Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, GA 30322, USA; Atlanta Veterans Administration Medical Center (VAMC), Decatur, GA 30033, USA. Electronic address: vin.tangpricha@emory.edu.
authors.forename: Vin
authors.initials: V
authors.lastname: Tangpricha
mesh_terms: D000328:Adult; D018798:Anemia, Iron-Deficiency / Q000097:blood / Q000150:complications / Q000178:diet therapy* / Q000453:epidemiology; D058070:Asymptomatic Diseases / Q000453:epidemiology / Q000628:therapy; D015415:Biomarkers / Q000097:blood; D002112:Calcifediol / Q000097:blood; D002762:Cholecalciferol / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood; D019587:Dietary Supplements / Q000009:adverse effects; D004311:Double-Blind Method; D015536:Down-Regulation; D005260:Female; D005293:Ferritins / Q000097:blood; D005845:Georgia / Q000453:epidemiology; D064451:Hepcidins / Q000097:blood*; D006801:Humans; D008297:Male; D009752:Nutritional Status; D010865:Pilot Projects; D015995:Prevalence; D014808:Vitamin D Deficiency / Q000097:blood / Q000150:complications / Q000178:diet therapy* / Q000453:epidemiology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016207:Cytokines; C578702:HAMP protein, human; D064451:Hepcidins; D002762:Cholecalciferol; D005293:Ferritins; D002112:Calcifediol
keywords: Anemia; Hepcidin; Inflammation; Iron; Vitamin D