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


      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.


      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.


      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 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.



      1,25(OH)2D (1,25-dihydroxyvitamin D), 25(OH)D (25-hydroxyvitamin D), BMI (body mass index), CKD (chronic kidney disease), GMR (geometric mean ratio), IL-1β (interleukin-1β), IL-6 (interleukin-6), IL-8 (interleukin-8), MCP-1 (monocyte chemoattractant protein-1)
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