REF-970 · Stoffel et al., 2017 · The Lancet Haematology, Vol. · Paper · PubMed

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

B+moderate evidenceMeasured on a mixed groupWritten before October 2026, being re-checked

Guidelines recommend daily iron divided through the day, but daily and split dosing may raise serum hepcidin and reduce absorption from the next dose. Two open-label randomised trials in iron-depleted women tested this with isotope-labelled ferrous sulfate.

Given on alternate days, the same doses were absorbed better — both as a fraction and in total — than on consecutive days, and hepcidin was lower. Splitting a daily dose in two did not improve absorption and raised hepcidin.

The authors conclude that alternate-day, single doses optimise absorption and might be a preferable regimen, to be confirmed in iron-deficient anaemic patients.

Participants

Women aged 18-40 years with depleted iron stores (serum ferritin ≤25 μg/L), recruited at ETH Zurich and the University of Zurich.

Study 1: 40 women — 21 in the consecutive-day group, 19 in the alternate-day group.
Study 2: 20 women — ten once-daily, ten twice-daily divided dosing, then crossed over.

Protocol

Study 1: 60 mg iron taken at 0800 h (±1 h) every day for 14 days, versus the same dose every other day for 28 days.
Study 2: a single 120 mg dose taken at 0800 h (±1 h) versus two 60 mg halves taken at 0800 h (±1 h) and at 1700 h (±1 h), on three days in a row; the groups switched regimens 14 days after the last dose.
Co-primary outcomes: serum hepcidin, and total and fractional iron absorption (measured from how much isotopic label had reached erythrocytes 14 days after dosing). Not masked; intention-to-treat.

Key Results

Study 1, cumulative fractional absorption: 16·3% (9·3, 28·8) consecutive-day versus 21·8% (13·7, 34·6) alternate-day (p=0·0013).
Study 1, cumulative total absorption: p=0·0010 for 131·0 mg (71·4, 240·5) on consecutive days against 175·3 mg (110·3, 278·5) on alternate days.
Serum hepcidin during the first 14 days was higher in the consecutive-day group (p=0·0031).
Study 2: no significant difference between once-daily and twice-daily dosing in fractional absorption (11·8% [7·1, 19·4] vs 13·1% [8·2, 20·7]; p=0·33) or total absorption (44·3 mg [29·4, 66·7] vs 49·4 [35·2, 69·4]; p=0·33); twice-daily doses gave higher serum hepcidin (p=0·013).
No grade 3 or 4 adverse events in either study.

Practical Application

In 40 iron-depleted women (ferritin ≤25 μg/L) randomised to 60 mg of iron every day for 14 days or every other day for 28 days, the alternate-day group absorbed more of the same total dose — 21·8% versus 16·3% fractional absorption, 175·3 mg versus 131·0 mg in total — with lower hepcidin; in a second trial of 20 women, splitting 120 mg into two daily doses did not improve absorption and raised hepcidin. To "should I take my iron every day or every other day?": this trial favours alternate days and a single morning dose, and the schedule itself is the prescribing doctor's call.
What was measured is absorption of labelled iron, not recovery of ferritin or haemoglobin: the alternate-day schedule also took twice as many days to deliver the same doses.
Inference, not tested here: the hepcidin explanation fits the base's habit of keeping iron away from hard sessions, since exercise also raises hepcidin (REF-340). Athletes were not studied.
Not from this paper; the base's own practice: iron is taken only on a blood test and a physician's advice (SYNTH-06).

Limitations

Absorption and hepcidin only: no ferritin, haemoglobin or performance outcome, and no symptoms beyond the absence of grade 3 or 4 adverse events.
Iron-depleted but not anaemic women; the authors say the findings should be confirmed in iron-deficient anaemic patients.
Not athletes, no men; training was not part of the design.
Open-label; the two schedules in study 1 ran over different numbers of days.
Written from the abstract and record metadata only (full text not read).
How this entry was checked and changed
Why this level

parallel RCT n=40 plus crossover n=20; the outcome is iron absorption and hepcidin, not iron status, haemoglobin or performance; non-athletes; graded conservatively