Plasma hepcidin is a modest predictor of dietary iron bioavailability in humans, whereas oral iron loading, measured by stable-isotope appearance curves, increases plasma hepcidin.
BACKGROUND
Plasma hepcidin appears to be a major regulator of iron absorption and homeostasis, but there are few data in humans.


OBJECTIVE
With the use of iron stable isotopes, we aimed to determine whether circulating hepcidin predicts dietary iron bioavailability, to quantify the amount of absorbed iron after oral iron loading, and to measure the plasma hepcidin response.


METHODS
In the first study, young women (n = 98) with an iron status varying from iron deficiency anemia to iron sufficiency (women with serum ferritin concentrations 25-40 microg/L were not included) were given stable isotope-labeled test meals (n = 196) containing ferrous sulfate, ferrous fumarate, or ferric pyrophosphate, after which plasma hepcidin and iron bioavailability were measured. In the second study, iron-sufficient men (n = 4) were given 3.8- and 60-mg oral doses of labeled ferrous sulfate. The stable isotope appearance curve was determined, and the plasma hepcidin response was measured over 6 h.


RESULTS
In study 1, plasma hepcidin and plasma ferritin were strongly correlated (r = 0.79, P < 0.001). Plasma hepcidin significantly, but modestly, predicted iron bioavailability from ferrous sulfate and ferrous fumarate (r = -0.51 and -0.46, respectively; P < 0.0001) but not from ferric pyrophosphate (r = -0.30, P = 0.056, respectively). In study 2, the 3.8-mg dose increased mean circulating absorbed iron to a peak of 0.42 micromol/L at 60 min but did not increase plasma hepcidin, The 60-mg dose increased mean circulating absorbed iron to a peak of 5.9 micromol/L at 120 min and produced an approximately 30% increase in mean plasma hepcidin at 6 h (P < 0.01).


CONCLUSIONS
Plasma hepcidin is only a modest predictor of dietary iron bioavailability in humans. Oral iron loading, measured by stable-isotope appearance curves, increases circulating hepcidin.
Zimmermann
Michael B
MB
Human Nutrition Laboratory, The Swiss Federal Institute of Technology, Zürich, Switzerland. michael.zimmermann@ilw.agrl.ethz.ch
Troesch
Barbara
B
Biebinger
Ralf
R
Egli
Ines
I
Zeder
Christophe
C
Hurrell
Richard F
RF
D000293:Adolescent; D000328:Adult; D023181:Antimicrobial Cationic Peptides / Q000097:blood*; D001682:Biological Availability; D015415:Biomarkers / Q000097:blood; D005260:Female; D005293:Ferritins / Q000097:blood; D005296:Ferrous Compounds / Q000493:pharmacokinetics; D064451:Hepcidins; D006801:Humans; D007408:Intestinal Absorption; D007501:Iron / Q000494:pharmacology*; D007503:Iron Isotopes / Q000493:pharmacokinetics; D019266:Iron, Dietary / Q000493:pharmacokinetics*; D008297:Male; D018579:Patient Selection; D011237:Predictive Value of Tests; D055815:Young Adult
D023181:Antimicrobial Cationic Peptides; D015415:Biomarkers; D005296:Ferrous Compounds; C578702:HAMP protein, human; D064451:Hepcidins; D007503:Iron Isotopes; D019266:Iron, Dietary; C020748:ferrous sulfate; D005293:Ferritins; D007501:Iron; C031621:ferrous fumarate