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

Abstract

Physicians and Surgeons, New York, NY Key Points• Iron supplements at doses of 60 mg Fe as FeSO 4 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.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 mg/L and conducted: (1) (study 1, n 5 25; study 2, n 5 16); and (2) a study giving three 60-mg Fe doses (twice-daily dosing) within 24 hours (study 3, n 5 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. (Blood.

How I treat anemia in pregnancy: iron, cobalamin, and folate

“…However, oral iron acutely increases hepcidin and recent data suggest that twice and thrice daily supplementation may have little added benefit over oncedaily dosing. 41 Two weeks after starting oral iron, a Hb increase of 1 g or more suggests adequate absorption. 42 Replacement should be continued until iron stores are replenished (generally 2-3 months), and 6 weeks postpartum.…”

Modern iron replacement therapy: clinical and pathophysiological insights

“…An already established major advance in oral iron therapy deriving from hepcidin discovery is related to the administration schedule. An elegant pilot-study by Moretti and colleagues on non-anemic ID premenopausal women suggested that giving oral iron on an alternate day schedule might be as effective as the classical daily schedule based on divided doses [81]. The classical schedule was associated to a rapid response in hepcidin production that limited the absorption of a second dose given too early.…”

The donation interval of 56 days requires extension to 180 days for whole blood donors to recover from changes in iron metabolism

“…17,18 Alternatively, and in the absence of point-of-care ferritin platforms, development of ID in donors may be prevented by (1) prolongation of donation intervals to 180 days in all donors as suggested by both the current and the REDS-III study 16 and/or (2) (low) dose iron supplementation. 24 …”