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 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.
Laboratory of Human Nutrition, Institute of Food Nutrition and Health, Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH Zürich), Zürich, Switzerland;
Diego
D
Moretti
Division of Hematology, University Hospital and University of Zürich, Zurich, Switzerland;
Jeroen S
JS
Goede
Laboratory of Human Nutrition, Institute of Food Nutrition and Health, Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH Zürich), Zürich, Switzerland;
Christophe
C
Zeder
Laboratory of Human Nutrition, Institute of Food Nutrition and Health, Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH Zürich), Zürich, Switzerland;
Markus
M
Jiskra
Laboratory of Human Nutrition, Institute of Food Nutrition and Health, Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH Zürich), Zürich, Switzerland;
Vaiya
V
Chatzinakou
Hepcidinanalysis.com and Department of Laboratory Medicine, Translational Metabolic Laboratory, Radboud University Medical Centre, Nijmegen, The Netherlands; and.
Harold
H
Tjalsma
Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands;
Alida
A
Melse-Boonstra
Laboratory of Human Nutrition, Institute of Food Nutrition and Health, Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH Zürich), Zürich, Switzerland; Department of Pediatrics, Columbia University, College of Physicians and Surgeons, New York, NY.
Gary
G
Brittenham
Hepcidinanalysis.com and Department of Laboratory Medicine, Translational Metabolic Laboratory, Radboud University Medical Centre, Nijmegen, The Netherlands; and.
Dorine W
DW
Swinkels
Laboratory of Human Nutrition, Institute of Food Nutrition and Health, Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH Zürich), Zürich, Switzerland;
Michael B
MB
Zimmermann
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001682:Biological Availability; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D018592:Cross-Over Studies; D019587:Dietary Supplements; D004334:Drug Administration Schedule; D005260:Female; D005293:Ferritins / Q000097:blood*; D005500:Follow-Up Studies; D064451:Hepcidins / Q000097:blood*; D006801:Humans; D007408:Intestinal Absorption; D007501:Iron / Q000032:analysis / Q000378:metabolism*; D019266:Iron, Dietary / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D055815:Young Adult
D015415:Biomarkers; D064451:Hepcidins; D019266:Iron, Dietary; D005293:Ferritins; D007501:Iron