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


Moretti, D; Goede, J S; Zeder, C; Jiskra, M; Chatzinakou, V; Tjalsma, H; Melse-Boonstra, A; Brittenham, G; Swinkels, D W; Zimmermann, M B (2015). Oral iron supplements increase hepcidin and decrease iron absorption from daily or twice-daily doses in iron-depleted young women. Blood, 126(17):1981-1989.

Abstract

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 [(57)Fe]-, [(58)Fe]-, or [(54)Fe]-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.

Abstract

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 [(57)Fe]-, [(58)Fe]-, or [(54)Fe]-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.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Hematology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:22 October 2015
Deposited On:09 Feb 2016 11:39
Last Modified:14 Feb 2018 11:04
Publisher:American Society of Hematology
ISSN:0006-4971
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1182/blood-2015-05-642223
PubMed ID:26289639

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