title: Diurnal rhythm rather than dietary iron mediates daily hepcidin variations.
abstract: BACKGROUND
  The iron-regulating hormone hepcidin is a promising biomarker in the diagnosis of iron disorders. Concentrations of hepcidin have been shown to increase during the day in individuals who are following a regular diet. It is currently unknown whether these increases are determined by an innate rhythm or by other factors. We aimed to assess the effect of dietary iron on hepcidin concentrations during the day.
  
  
  METHODS
  Within a 7-day interval, 32 volunteers received an iron-deficient diet on 1 day and the same diet supplemented with 65 mg ferrous fumarate at 0815 and 1145 on another day. Blood was drawn to assess ferritin, hepcidin-25, and transferrin saturation (TS) throughout both days at 4 time points between 0800 (fasted) and 1600. A linear mixed model for repeated data was used to analyze the effect of iron intake on TS and hepcidin concentrations.
  
  
  RESULTS
  Baseline values of hepcidin at 0800 correlated significantly with ferritin (r = 0.61). During the day of an iron-deficient diet the mean TS was similar both in men and in women, whereas hepcidin increased. During the day with iron supplementation the mean TS was significantly higher both in men and in women, and the mean hepcidin was moderately but significantly higher in women (1.0 nmol/L, 95% CI, 0.2-1.8) but not in men (0.0 nmol/L, 95% CI, -0.8 to 0.8).
  
  
  CONCLUSIONS
  Our data demonstrate that ferritin sets the basal hepcidin concentrations and suggest that innate diurnal rhythm rather than dietary iron mediates the daily hepcidin variations. These findings will be useful for optimizing sampling protocols and will facilitate the interpretation of hepcidin as an iron biomarker.
authors.affiliation: Laboratory of Genetic, Endocrine and Metabolic Diseases, Department of Laboratory Medicine, Radboud University Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands.
authors.forename: Charlotte C M
authors.initials: CC
authors.lastname: Schaap
authors.forename: Jan C M
authors.initials: JC
authors.lastname: Hendriks
authors.forename: Guus A M
authors.initials: GA
authors.lastname: Kortman
authors.forename: Siem M
authors.initials: SM
authors.lastname: Klaver
authors.forename: Joyce J C
authors.initials: JJ
authors.lastname: Kroot
authors.forename: Coby M M
authors.initials: CM
authors.lastname: Laarakkers
authors.forename: Erwin T
authors.initials: ET
authors.lastname: Wiegerinck
authors.forename: Harold
authors.initials: H
authors.lastname: Tjalsma
authors.forename: Mirian C H
authors.initials: MC
authors.lastname: Janssen
authors.forename: Dorine W
authors.initials: DW
authors.lastname: Swinkels
mesh_terms: D000293:Adolescent; D000328:Adult; D023181:Antimicrobial Cationic Peptides / Q000097:blood*; D002940:Circadian Rhythm; D019587:Dietary Supplements; D005260:Female; D005293:Ferritins / Q000097:blood; D064451:Hepcidins; D006801:Humans; D019266:Iron, Dietary / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D014168:Transferrin / Q000032:analysis
chemical_list: D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; D064451:Hepcidins; D019266:Iron, Dietary; D014168:Transferrin; D005293:Ferritins