Plasma hepcidin concentrations significantly predict interindividual variation in iron absorption in healthy men

Background: Iron absorption is proposed to be regulated by circulating hepcidin, but, to date, little data are available to evaluate this relation in humans. Objective: Stored samples from a human iron absorption study were used to test the hypothesis that differences in plasma hepcidin explain interindividual variation in iron absorption. Design: Hepcidin-25 concentrations were measured in fasting samples from men aged ≥40 y (n = 33) recruited to a study investigating the relation between the HFE genotype, iron absorption, and iron status. Results: Log iron absorption was negatively correlated with serum ferritin (r = −0.59, P < 0.001) and with plasma hepcidin (r = −0.55, P < 0.001) but was unaffected by genotype. There was a positive correlation (r = 0.82, P < 0.001) between hepcidin (mean: 2.3; range: 0.1–7.8 nmol/L) and ferritin (mean: 70; range: 9–208 μg/L). Multiple linear regression models showed that plasma hepcidin in isolation significantly predicted 36% of the interindividual variation in iron absorption. Conclusions: Plasma hepcidin and serum ferritin concentrations are highly correlated, and, in the normal range of plasma hepcidin values, 36% of interindividual differences in iron absorption are explained by differences in circulating plasma hepcidin.