High-dose vitamin D3 reduces circulating hepcidin concentrations: A pilot, randomized, double-blind, placebo-controlled trial in healthy adults

Clin Nutr. 2017 Aug;36(4):980-985. doi: 10.1016/j.clnu.2016.06.015. Epub 2016 Jun 27.

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 D3 on 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 D3 or 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 D3 significantly 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.

Keywords: Anemia; Hepcidin; Inflammation; Iron; Vitamin D.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Anemia, Iron-Deficiency / blood
  • Anemia, Iron-Deficiency / complications
  • Anemia, Iron-Deficiency / diet therapy*
  • Anemia, Iron-Deficiency / epidemiology
  • Asymptomatic Diseases / epidemiology
  • Asymptomatic Diseases / therapy
  • Biomarkers / blood
  • Calcifediol / blood
  • Cholecalciferol / administration & dosage*
  • Cholecalciferol / adverse effects
  • Cholecalciferol / therapeutic use
  • Cohort Studies
  • Cytokines / blood
  • Dietary Supplements* / adverse effects
  • Double-Blind Method
  • Down-Regulation*
  • Female
  • Ferritins / blood
  • Georgia / epidemiology
  • Hepcidins / blood*
  • Humans
  • Male
  • Nutritional Status*
  • Pilot Projects
  • Prevalence
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / complications
  • Vitamin D Deficiency / diet therapy*
  • Vitamin D Deficiency / epidemiology
  • Young Adult

Substances

  • Biomarkers
  • Cytokines
  • HAMP protein, human
  • Hepcidins
  • Cholecalciferol
  • Ferritins
  • Calcifediol