Daily oral iron supplementation produced greater improvements in hematological parameters than alternate day doses - A pilot double-blind randomized control trial in iron-deficient young women.

BACKGROUND AND AIMS: There is little universal consensus on the optimal regime for oral iron supplementation to treat iron deficiency (ID) and iron-deficiency anemia (IDA) in women of reproductive age (WRA). A few studies in a high-income country have reported higher fractional absorption from oral iron supplements (OIS) given on alternate days than daily doses; however, there were no significant improvements in hematological indices in the women in these studies who received the alternate-day doses. There are also concerns about adverse gastrointestinal effects resulting from daily OIS. Data on these aspects from low and middle-income countries (LMIC), where the burden of IDA is high, are limited.

METHODS

We conducted a double-blinded, parallel-arm, non-inferiority, randomized controlled trial in non-pregnant WRA aged 18-45 years with ID (serum ferritin <20 μg/L) (CTRI/2020/03/024144). They were randomized to receive either 60 mg elemental iron daily (n = 30) or 120 mg elemental iron on alternate days (n = 30) for 14 days. The primary outcome was to determine the comparative effectiveness of daily versus alternate-day OIS in improving hematological and iron-related parameters in blood, at the end of the intervention. Secondary outcomes included extent of adherence to intervention, adverse events experienced, and changes in fecal calprotectin concentrations (a marker of gut inflammation) and the gut microbiome profile.

RESULTS

Adherence to the regimes was excellent (≥90 %) in both arms. Both regimes significantly improved hematological and iron-related parameters in blood at the end of 14 days. Daily OIS resulted in greater increases in mean corpuscular volume (fL) [1.25 (0.25, 2.32) vs. 0.50 (-0.35, 1.42); p = 0.043], mean corpuscular hemoglobin (pg/cell) [0.52 (0.54) vs. 0.17 (0.56); p = 0.019], and reticulocyte counts (%) [0.32 (0.13, 0.75) vs. 0.27 (0.02, 0.45); p = 0.055] than alternate-day doses. There were no significant differences between the groups in extent of improvements in iron-related parameters, incidence of adverse effects, and effects on gut inflammation and microbiome profile.

CONCLUSION

In iron-deficient WRA in an LMIC setting, daily OIS (60 mg) for 14 days was more effective than equivalent amounts on alternate days in improving hematological parameters.