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Every Other Day Dosing with Iron Sulphate Just as Effective as Daily Dosing in Premenopausal Women

Iron deficiency is the most common cause of anemia in the world. In 2019, the WHO estimated the global prevalence of anemia to be 29.6% in non-pregnant women. Iron deficiency anemia is thought to account for about 50% of all cases of anemia in women. Many of the current guidelines recommend that patients with iron deficiency anemia use iron supplements daily in attempt to bring the ferritin and hemoglobin levels back up to a normal range.

One of the issues with daily iron absorption are the side effects. Some patients have constipation and some have other GI upset issues like diarrhea. Some have nausea, dyspepsia, metallic taste in the mouth, epigastric discomfort which may reduce compliance to the treatment and long-term efficacy.

Furthermore, daily iron use may stimulate increased production of the protein hepcidin which may act to block further absorption. Some authors have been interested in studying whether daily iron use may actually be less effective than use every other day because of the fact that hepcidin gets stimulated to such a great extent in those that use daily.

To really understand this issue better, it’s helpful for us to first review a really important landmark study from 2017 as well as some additional study. Then we’ll come back to a new one by Kaynar et al after that.

Stoffel NU et al. 2017

The Stoffel study showed us that taking iron every other day is probably just as effective (and perhaps more effective) as taking it daily. In the study, women were randomly assigned to two groups. One group was given 60 mg iron (as ferrous sulphate) in the morning on consecutive days for 14 days, and the other group was given the same doses on alternate days for twice as long – 28 days. 40 women were enrolled in the study. 21 women received daily iron and 19 received iron every other day. At the end of treatment (14 days for the consecutive-day group and 28 days for the alternate-day group), cumulative total iron absorption was 131 mg in the daily group compared to 175 mg in the every other day group. Serum hepcidin levels were greater in the consecutive-day group than the alternate-day group (p=0 0031).

Mehta S et al. 2020

In 2020 Mehta et al compared daily vs every other day iron supplementation in 40 patients (20 in each group. The authors showed that alternate day single tablet dosing schedule of oral iron therapy (60mg of elemental iron, ferrous sulfate) was more effective and better tolerated compared to daily supplementation in IDA.The authors showed that hepcidin levels increased more in the group using daily iron.

Kaynar et al. 2022

A new study set out to compare the effectiveness of daily vs every other day oral iron replacement therapy in women of reproductive age (18-50) with iron-deficiency anemia.

The authors included premenopausal female patients aged between 18 and 50 years with iron-deficiency anemia (hemoglobin<12 g/dl, ferritin<30 mcg/l, and/or transferrin saturation<15%).

Forty patients were given oral iron therapy at a daily dose of 160 mg (iron sulfate). Forty-three patients were given iron treatment at a dose of 160 mg (iron sulfate) every other day. After 2 months of oral iron therapy, there was a significant improvement in hemoglobin, mean corpuscular volume, serum iron, total iron binding capacity, and transferrin saturation in both groups. Overall, there were no differences between the groups suggesting that they both appear to be similarly effective. Hepcidin levels did not differ in a statistically significant way between the groups although levels did, of course, increase with iron therapy.

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