Diurnal Rhythm rather than Dietary Iron Mediates Daily Hepcidin Variations
Open Access
- 1 March 2013
- journal article
- Published by Oxford University Press (OUP) in Clinical Chemistry
- Vol. 59 (3), 527-535
- https://doi.org/10.1373/clinchem.2012.194977
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.Keywords
This publication has 26 references indexed in Scilit:
- Hepcidin in Human Iron Disorders: Diagnostic ImplicationsClinical Chemistry, 2011
- A time course of hepcidin response to iron challenge in patients with HFE and TFR2 hemochromatosisHaematologica, 2010
- Two to Tango: Regulation of Mammalian Iron MetabolismCell, 2010
- Plasma hepcidin is a modest predictor of dietary iron bioavailability in humans, whereas oral iron loading, measured by stable-isotope appearance curves, increases plasma hepcidinThe American Journal of Clinical Nutrition, 2009
- (Pre)analytical imprecision, between-subject variability, and daily variations in serum and urine hepcidin: Implications for clinical studiesAnalytical Biochemistry, 2009
- Development of a novel immunoassay for the iron regulatory peptide hepcidinBritish Journal of Biomedical Science, 2009
- Immunoassay for human serum hepcidinPublished by American Society of Hematology ,2008
- Mass Spectrometry–Based Hepcidin Measurements in Serum and Urine: Analytical Aspects and Clinical ImplicationsClinical Chemistry, 2007
- Cis and trans regulation of hepcidin expression by upstream stimulatory factorBlood, 2006
- IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidinJCI Insight, 2004