The summary of 2 small studies (by the same leading author) is that fractional iron absorption (the percent of iron from a given dose absorbed) is greater by 30-50% with supplementation every other day than every day, BUT the total iron absorption in a given period is about the same, so it does not result in a quicker normalization of the iron status. The alternative day regime may be associated with fever side effects, though.
First study
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 (The Lancet Haematology, 2017)
Different groups of women aged 18-40 who were "iron-depleted," but not necessary anemic, (serum ferritin ≤25 μg/L), took oral radioactively labelled isotopes of iron supplements (ferrous sulfate). They divided the study into 2 studies:
Study 1 (iron absorption):
- 60 mg/day once a day for 14 days (cumulative total absorbed dose: 131·0 mg [71·4 - 240·5 mg])
- 60 mg/day every other day for 28 days, so the same total dose as in 1. (cumulative total absorbed dose: 175·3 mg [110·3 - 278·5 mg])
NOTE, that in the regime 1, the cumulative total absorbed dose (131 mg) was in 14 days, while in the regime 2 the dose (175.3 mg) was in 28 days, which means that in the alternative day regime more iron was absorbed from the same total dose as in every day regime, but in a period twice as long.
Study 2 (hepcidin levels):
- 120 mg/day once a day for 3 days
- 60 mg twice a day for 3 days, so the same daily and total dose as in 3. (At the end, this group had higher serum hepcidin levels.)
Hepcidin is a protein synthesized in the liver and detected in the blood.
High hepcidin levels block intestinal iron absorption (Frontiers in Physiology, 2019).
Interpretation of the study by the authors:
In iron-depleted women, providing iron supplements daily as divided
doses increases serum hepcidin and reduces iron absorption.
Providing iron supplements on alternate days and in single doses optimises iron absorption and might be a preferable dosing regimen.
These findings should be confirmed in iron-deficient anaemic patients.
Second study
This was a study in anemic women (mean serum ferritin ~10 μg/L).
Iron absorption from supplements is greater with alternate day than with consecutive day dosing in iron-deficient anemic women (Haematologica, 2019):
Alternate day dosing of oral iron supplements in anemic women may be
preferable because it sharply increases fractional iron absorption. In
order to provide the same total amount of iron with alternate day
dosing, twice the daily target dose should be given on alternate days
as total iron absorption from a single dose of 200 mg given on
alternate days was approximately twice that from 100 mg given on
consecutive days (p<0.001).
BUT
Consequently, TIA from a single dose of 200 mg given on alternate days
was approximately twice that from 100 mg given on consecutive days
(p<0.001). This suggests that TIA would be similar from alternate
day dosing of 200 mg compared to daily dosing of 100 mg. (TIA =
total iron absorption)
but:
In conclusion, as in our previous studies using a daily dose of 60 mg
in iron-depleted nonanemic women, our data show that with higher doses
of 100-200 mg iron in women with IDA, alternate day dosing results in
higher FIA and a trend for lower incidence of gastrointestinal side
effects compared to consecutive day dosing. (IDA = iron deficiency anemia, FIA = fractional iron absorption)
but:
These potential benefits need to be confirmed in long-term
intervention studies in anemic women with clinical endpoints, such as
change in Hb, iron status and side effects, as primary outcomes.
