Oral iron supplements increase hepcidin and decrease iron absorption from daily or twice-daily doses in iron-depleted young women

Iron supplements acutely increase hepcidin, but the duration and magnitude of the increase, its dose dependence, and its effects on subsequent iron absorption have not been characterized in humans. Better understanding of these phenomena might improve oral iron dosing schedules. We investigated whet...

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Bibliographic Details
Published in:	Blood Vol. 126; no. 17; pp. 1981 - 1989
Main Authors:	Moretti, Diego, Goede, Jeroen S., Zeder, Christophe, Jiskra, Markus, Chatzinakou, Vaiya, Tjalsma, Harold, Melse-Boonstra, Alida, Brittenham, Gary, Swinkels, Dorine W., Zimmermann, Michael B.
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 22-10-2015
Subjects:	Administration, Oral Adolescent Adult Biological Availability Biomarkers - blood Case-Control Studies Chair Nutrition and Health over the Lifecourse Cross-Over Studies Dietary Supplements Drug Administration Schedule Female Ferritins - blood Follow-Up Studies Global Nutrition Hepcidins - blood HNE Nutrition and Health over the Lifecourse HNE Voeding en Gezondheid in de Levenscyclus Humans Intestinal Absorption Iron - analysis Iron - metabolism Iron, Dietary - administration & dosage Iron, Dietary - pharmacokinetics Male Middle Aged Prognosis VLAG Wereldvoeding Young Adult
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Summary:	Iron supplements acutely increase hepcidin, but the duration and magnitude of the increase, its dose dependence, and its effects on subsequent iron absorption have not been characterized in humans. Better understanding of these phenomena might improve oral iron dosing schedules. We investigated whether the acute iron-induced increase in hepcidin influences iron absorption of successive daily iron doses and twice-daily iron doses. We recruited 54 nonanemic young women with plasma ferritin ≤20 µg/L and conducted: (1) a dose-finding investigation with 40-, 60-, 80-, 160-, and 240-mg labeled Fe as [57Fe]-, [58Fe]-, or [54Fe]-FeSO4 given at 8:00 am fasting on 1 or on 2 consecutive days (study 1, n = 25; study 2, n = 16); and (2) a study giving three 60-mg Fe doses (twice-daily dosing) within 24 hours (study 3, n = 13). In studies 1 and 2, 24 hours after doses ≥60 mg, serum hepcidin was increased (P < .01) and fractional iron absorption was decreased by 35% to 45% (P < .01). With increasing dose, fractional absorption decreased (P < .001), whereas absolute absorption increased (P < .001). A sixfold increase in iron dose (40-240 mg) resulted in only a threefold increase in iron absorbed (6.7-18.1 mg). In study 3, total iron absorbed from 3 doses (2 mornings and an afternoon) was not significantly greater than that from 2 morning doses. Providing lower dosages (40-80 mg Fe) and avoiding twice-daily dosing maximize fractional absorption. The duration of the hepcidin response supports alternate day supplementation, but longer-term effects of these schedules require further investigation. These clinical trials were registered at www.ClinicalTrials.gov as #NCT01785407 and #NCT02050932. •Iron supplements at doses of 60 mg Fe as FeSO4 or higher increase hepcidin for up to 24 hours and are associated with lower iron absorption on the following day.•The soluble transferrin receptor/ferritin ratio and hepcidin are equivalent predictors of iron absorption from supplements.
ISSN:	0006-4971 1528-0020
DOI:	10.1182/blood-2015-05-642223