Daily administration of oral iron is considered the current treatment standard for treating iron deficiency anemia due to availability and reduced cost compared to intravenous iron therapy. But adverse effects like epigastric pain, heartburn, and constipation reduce compliance to daily oral iron. There is scanty evidence regarding compliance and efficacy with alternate-day iron therapy. As per our knowledge, this is the first systematic review to compare daily with alternate-day oral iron therapy. Six electronic databases including PubMed and EMBASE were searched for randomized controlled trials, quasi-experimental studies published between January 2000 to March 2023 that compared daily with alternate day iron therapy in individuals diagnosed with iron deficiency anemia. The primary outcome analyzed was a change in hemoglobin. The other hematological parameters were assessed as secondary outcomes. Risk of bias was assessed regarding randomization process, deviation from intended intervention, missing outcome data, measurement of the outcome, and selection of the reported result. Out of the 9 full-text articles, 2 were not included as one was an ongoing trial and the second one had a different study design. The reviewed trials involved 594 participants, and the study participants ranged from 19 to 200. The mean age of the participants in the reported trials was 21 ± 2 to 49 ± 16 years. There is no significant increase in hemoglobin level and also the iron indices namely ferritin, hepcidin, total iron binding capacity, and reticulocyte count between daily and alternate-day dosing of iron. However, the frequency of adverse effects especially nausea, metallic taste, and altered bowel habits are reduced with alternate-day dosing. Oral iron given daily or on alternate days did not have a significant difference in the hemoglobin levels though iron absorption may be affected in the initial few days. Trial registration: The review protocol was registered with PROSPERO (Prospero2023CRD42023393095).
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