By Jessica Orner, MD

Family Medicine Physician, Lebanon, PA

Dr. Orner reports no financial relationships relevant to this field of study.

SYNOPSIS: In a cohort of 19 women with iron deficiency anemia, alternate-day doses of iron led to 40-50% more iron absorption compared to consecutive-day doses.

SOURCE: Stoffel NU, Zeder C, Brittenham GM, et al. Iron absorption from supplements is greater with alternate day than with consecutive day dosing in iron-deficient anemic women. Haematologica 2019. pii:haematol.2019.220830. doi:10.3324/haematol.2019.220830.

Researchers in this study evaluated iron absorption in women with iron deficiency anemia using an alternate-day administration. Study participants were recruited from otherwise healthy women participating in a blood donation drive in Switzerland. A cohort of 19 women participated in two study cycles of six days in length, with 16 days between the cycles. The participants were randomly assigned to receive three doses of either 100 mg or 200 mg of ferrous sulfate on days 2, 3, and 5 of the study cycles. If the participant received 100 mg during the first cycle, she received 200 mg during the second and vice versa. The median hemoglobin level was 11.5 mg/dL.

The authors measured iron absorption by labeling the ferrous sulfate with iron isotopes. The doses administered on days 2, 3, and 5 each included a different isotope label. Iron absorption was assessed by measuring isotopic enrichment in red blood cells 16 days after the third dose of ferrous sulfate was administered. Fractional iron absorption was found to be 40-50% higher on day 2 and day 5 compared to day 3 (P < 0.001). Absorption on day 2 and day 5 did not differ significantly from each other, meaning that 40-50% more iron was absorbed when there were at least 24 hours between iron doses compared to consecutive days of dosing.

Stoffel et al also evaluated serum hepcidin levels in relation to iron absorption as a secondary outcome in women with iron deficiency. Hepcidin is the main regulator of iron in the body. High serum hepcidin levels are associated with decreased dietary iron absorption and storage.1 There is a theory that enterocytes exposed to large doses of iron do not absorb subsequent iron doses over the next five to six days, also known as the “mucosal block” theory. The researchers aimed to evaluate if there was a continued decrease in iron absorption after the serum hepcidin levels tapered that may be linked to decreased enterocyte absorption. In this study, hepcidin levels did increase after iron intake, and those increases persisted for 24 hours. There was not a decrease in iron absorption after 48 hours, which argues against the “mucosal block” theory. From this study, it would be difficult to know if there was any mucosal block in the first 24 hours due to the confounding presence of hepcidin.

While small, this study provides evidence that alternate-day dosing of iron would be beneficial in women with iron deficiency. It showed that they exhibited increased serum hepcidin levels and decreased absorption of iron for at least the first 24 hours after a dose of 100 mg to 200 mg of ferrous sulfate. Based on this information and the information already known about hepcidin’s role in iron absorption, clinicians should consider counseling iron-deficient patients to take their iron supplements every other day for better absorption.

While alternate-day dosing of iron may lead to better absorption, there is concern about adherence to an alternate dosing schedule. It would be interesting to see a future study on adherence to this type of schedule to determine efficacy.


  1. Rossi E. Hepcidin - the iron regulatory hormone. Clin Biochem Rev 2005;26:47-49.