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Vitamin D Reduces Hepcidin Concentrations Independent of Inflammatory Cytokines in Healthy Adults: A Pilot, Randomized, Double‐Blind, Placebo‐Controlled Trial of High‐Dose Vitamin D 3
Author(s) -
Smith Ellen,
Alvarez Jessica,
Kearns Malcolm,
Hao Li,
Sloan John,
Konrad Robert,
Ziegler Thomas,
Zughaier Susu,
Tangpricha Vin
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.916.13
Subject(s) - hepcidin , ferritin , vitamin d and neurology , placebo , medicine , cytokine , proinflammatory cytokine , endocrinology , inflammation , vitamin , vitamin d deficiency , immunology , pathology , alternative medicine
Objective Disturbances in iron recycling may result from elevations in pro‐inflammatory cytokines and hepcidin, the major iron‐regulatory hormone. In vitro studies suggest that vitamin D may reduce hepcidin and pro‐inflammatory cytokines, and vitamin D deficiency is associated with increased odds of anemia of inflammation. However, data from clinical trials assessing the vitamin D‐mediated effects on iron recycling in healthy individuals are lacking. Our objectives were to: 1) examine the effect of high‐dose vitamin D on plasma hepcidin, inflammatory cytokine, and ferritin concentrations in healthy adults; and 2) determine whether any observed changes in hepcidin were concomitant with or independent of changes in pro‐inflammatory cytokines. 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 D 3 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 randomized groups; 75% of subjects had plasma 25(OH)D concentrations < 20 ng/mL. After 1 week, plasma hepcidin concentrations had decreased significantly from baseline by 73% in those who received vitamin D 3 (geometric mean ratio [GMR]: 0.27 (95% CI: 0.11, 0.62); P =0.005) compared to no significant change with placebo (GMR: 0.73 (95% CI: 0.49, 1.09); P =0.11). Plasma cytokine and ferritin concentrations did not change significantly in either group. Conclusion High‐dose vitamin D 3 significantly reduced plasma hepcidin concentrations in healthy adults 1 week post‐dosing, while no change was observed in pro‐inflammatory cytokine or ferritin concentrations. These findings suggest that vitamin D may have a role in regulating iron recycling by acting directly on hepcidin, independent of changes in inflammatory markers; however, down‐stream effects on markers of iron status in the absence of inflammatory conditions remain unclear. Longer follow‐up and evaluation of additional markers of iron status may be required. Support or Funding Information T32 DK007734 (EMS), K01 DK102851 (JAA), K24 DK096574 (TRZ), UL1 TR000454 (TRZ, VT)