PMID- 27402475 OWN - NLM STAT- MEDLINE DCOM- 20180326 LR - 20220408 IS - 1532-1983 (Electronic) IS - 0261-5614 (Print) IS - 0261-5614 (Linking) VI - 36 IP - 4 DP - 2017 Aug TI - High-dose vitamin D(3) reduces circulating hepcidin concentrations: A pilot, randomized, double-blind, placebo-controlled trial in healthy adults. PG - 980-985 LID - S0261-5614(16)30148-0 [pii] LID - 10.1016/j.clnu.2016.06.015 [doi] AB - 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 D(3) 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 D(3) or placebo. Between- and within-group differences in plasma hepcidin, pro-inflammatory cytokine [interleukin (IL)-1beta, 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 D(3) (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 D(3) 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. CI - Published by Elsevier Ltd. FAU - Smith, Ellen M AU - Smith EM AD - Nutrition and Health Sciences Program, Laney Graduate School, Emory University, Atlanta, GA 30322, USA. FAU - Alvarez, Jessica A AU - Alvarez JA AD - 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. FAU - Kearns, Malcolm D AU - Kearns MD AD - Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, GA 30322, USA. FAU - Hao, Li AU - Hao L AD - Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, GA 30322, USA. FAU - Sloan, John H AU - Sloan JH AD - Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA. FAU - Konrad, Robert J AU - Konrad RJ AD - Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA. FAU - Ziegler, Thomas R AU - Ziegler TR AD - 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. FAU - Zughaier, Susu M AU - Zughaier SM AD - Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA; Atlanta Veterans Administration Medical Center (VAMC), Decatur, GA 30033, USA. FAU - Tangpricha, Vin AU - Tangpricha V AD - 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. LA - eng GR - K01 DK102851/DK/NIDDK NIH HHS/United States GR - K24 DK096574/DK/NIDDK NIH HHS/United States GR - T32 DK007734/DK/NIDDK NIH HHS/United States GR - UL1 TR000454/TR/NCATS NIH HHS/United States PT - Journal Article PT - Randomized Controlled Trial DEP - 20160627 PL - England TA - Clin Nutr JT - Clinical nutrition (Edinburgh, Scotland) JID - 8309603 RN - 0 (Biomarkers) RN - 0 (Cytokines) RN - 0 (HAMP protein, human) RN - 0 (Hepcidins) RN - 1C6V77QF41 (Cholecalciferol) RN - 9007-73-2 (Ferritins) RN - P6YZ13C99Q (Calcifediol) SB - IM MH - Adult MH - Anemia, Iron-Deficiency/blood/complications/*diet therapy/epidemiology MH - Asymptomatic Diseases/epidemiology/therapy MH - Biomarkers/blood MH - Calcifediol/blood MH - Cholecalciferol/*administration & dosage/adverse effects/therapeutic use MH - Cohort Studies MH - Cytokines/blood MH - *Dietary Supplements/adverse effects MH - Double-Blind Method MH - *Down-Regulation MH - Female MH - Ferritins/blood MH - Georgia/epidemiology MH - Hepcidins/*blood MH - Humans MH - Male MH - *Nutritional Status MH - Pilot Projects MH - Prevalence MH - Vitamin D Deficiency/blood/complications/*diet therapy/epidemiology MH - Young Adult PMC - PMC5191989 MID - NIHMS798745 OTO - NOTNLM OT - Anemia OT - Hepcidin OT - Inflammation OT - Iron OT - Vitamin D COIS- Conflict of interest: JHS and RJK are employed by Eli Lilly and Company and performed the hepcidin assay. Eli Lilly and Company played no role in the study design or decision to publish. EDAT- 2016/07/13 06:00 MHDA- 2018/03/27 06:00 PMCR- 2018/08/01 CRDT- 2016/07/13 06:00 PHST- 2016/02/04 00:00 [received] PHST- 2016/06/14 00:00 [revised] PHST- 2016/06/20 00:00 [accepted] PHST- 2016/07/13 06:00 [pubmed] PHST- 2018/03/27 06:00 [medline] PHST- 2016/07/13 06:00 [entrez] PHST- 2018/08/01 00:00 [pmc-release] AID - S0261-5614(16)30148-0 [pii] AID - 10.1016/j.clnu.2016.06.015 [doi] PST - ppublish SO - Clin Nutr. 2017 Aug;36(4):980-985. doi: 10.1016/j.clnu.2016.06.015. Epub 2016 Jun 27.