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Daily vs Alternate-Day Oral Iron Therapy

Information sourced from NEJM Journal Watch:

Daily vs. Alternate-Day Oral Iron Therapy

A small study suggests some advantages for alternate-day dosing.

In a second experiment, 20 women received either 120 mg of iron once daily or 60 mg twice daily for 3 days; after a 2-week washout period, each participant crossed over to the other regimen. The two regimens did not differ in fractional or total iron absorption, but with both regimens, absorption was higher on the first day than on the second and third days.

Oral iron therapy is plagued by relatively poor absorption and gastrointestinal side effects. In a previous 2-day study, researchers demonstrated that fractional iron absorption is suppressed by high doses of oral iron (compared with lower doses) and by twice-daily dosing (compared with once-daily dosing; NEJM JW Gen Med Dec 1 2015 and Blood 2015; 126:1981). Now, the researchers have extended their previous observations.

They recruited healthy young Swiss women with low or low-normal iron stores (serum ferritin levels, ≤25 μg/L) and normal or only mildly low hemoglobin levels. In one experiment, 40 participants were randomized to receive 60 mg of iron (as ferrous sulfate) either every morning for 14 days or on alternate mornings for 28 days. At the end of these dosing periods, both fractional absorption and cumulative total absorption of iron were significantly greater in the alternate-day group than in the daily group.


Alternate-day oral iron dosing is associated with better fractional absorption of iron than is daily dosing; the presumed mechanism is that iron intake raises levels of hepcidin (which blocks the absorption of iron given the following day). This study was too small and too short to allow reliable assessment of side effects, but gastrointestinal tolerability likely would be enhanced with alternate-day dosing. The next step will be to compare daily and alternate-day regimens in patients with substantial iron deficiency anemia.

Allan S. Brett, MD reviewing Stoffel NU et al. Lancet Haematol 2017 Oct 9.

Stoffel NU et al. Iron absorption from oral iron supplements given on consecutive versus alternate days and as single morning doses versus twice-daily split dosing in iron-depleted women: Two open-label, randomised controlled trials. Lancet Haematol 2017 Oct 9; [e-pub].

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