Every-other-day iron supplementation may offer better absorption

Two open-label randomized controlled trials assessed iron absorption in iron-depleted women.


Taking iron supplements daily as divided doses increases serum hepcidin levels and reduces iron absorption, while taking them on alternate days and in single doses optimizes iron absorption and might be a preferable dosing regimen, a study found.

Researchers conducted two open-label randomized controlled trials assessing iron absorption in iron-depleted women (serum ferritin level ≤25 μg/L) ages 18 to 40 years in Switzerland. Within-individual comparisons were done. The primary outcomes in both studies were iron bioavailability (total and fractional iron absorption) and serum hepcidin level. Results were published online Oct. 9 by The Lancet Haematology.

In the first study, 40 women were randomly assigned to either 60 mg of iron in the morning on consecutive days for 14 days or the same doses on alternate days for 28 days. At the end of treatment (14 days for the consecutive-day group and 28 days for the alternate-day group), geometric mean cumulative fractional iron absorptions were 16.3% in the consecutive-day group versus 21.8% in the alternate-day group (P=0.0013), and cumulative total iron absorption was 131.0 mg versus 175.3 mg (P=0.0010). During the first 14 days of supplementation in both groups, serum hepcidin level was higher in the consecutive-day group than the alternate-day group (P=0.0031).

In the second study, women were assigned to two groups stratified by serum ferritin level so that two groups with similar iron statuses could be formed. One group was given 120 mg of iron in the morning (n=10), and the other was given the dose split into two divided doses of 60 mg in the morning and evening for three consecutive days (n=10). Fourteen days after the final dose, the groups were each crossed over to the other regimen.

No significant differences were seen in fractional or total iron absorption between the two dosing regimens. Twice-daily divided doses resulted in a higher serum hepcidin concentration than once-daily dosing (P=0.013). No grade 3 or 4 adverse events were reported in either study.

These findings should be confirmed in iron-deficient anemic patients, the authors wrote. “By contrast with most current recommendations on iron supplementation, our findings suggest that providing oral iron on alternate days in single morning doses increases iron absorption in young women and is an effective regimen to optimise iron absorption,” the authors wrote. “This regimen not only improves iron absorption but also, because of its simplicity, might increase compliance.”

An editorial noted that minor adverse events, nausea and abdominal pain, that are typically associated with iron supplementation occurred and that constipation was not reported in the study. “Nonetheless, those of us who treat anaemia should be grateful for these fascinating observations, which are likely to lead to a more felicitous means of administering this widely used therapy for one of the most common maladies, which remains complicated with poor tolerability and adherence,” the editorial stated. and

ACP Internist outlined expert tips on iron absorption, including less frequent dosing, in its June 2017 issue.