Reduced-dose alternate-day oral iron supplementation in women with iron deficiency: a randomized controlled trial

Oral iron supplementation is frequently limited by gastrointestinal side effects and reduced absorption associated with hepcidin-mediated regulation. This randomized, parallel-group, active-controlled study evaluated whether a reduced-dose alternate-day oral iron supplementation strategy could improve iron status in women with iron deficiency. Sixty-six iron-deficient women of reproductive age (18–50 years; serum ferritin < 30 ng/mL) were randomized to receive, for 42 days, either micronized, dispersible ferric pyrophosphate providing 21 mg of elemental iron every 48 h combined with a daily gut microbiota modulator, or sucrosomial ferric pyrophosphate providing 30 mg of elemental iron per day. The primary endpoint was serum ferritin, while secondary endpoints included serum iron, transferrin, transferrin saturation (TSAT), total iron-binding capacity (TIBC), hemoglobin, and red blood cell count. Serum ferritin increased significantly over time in both groups ( p < 0.001), with no significant differences between treatments. Comparable improvements were observed for serum iron, transferrin, TSAT, and TIBC, while hemoglobin remained stable throughout the study. Both interventions were generally well tolerated, with only mild transient gastrointestinal adverse events and no clinically relevant changes in inflammatory markers. A reduced-dose alternate-day oral iron supplementation strategy achieved improvements in iron status comparable to standard daily supplementation despite lower cumulative iron exposure. These findings support the potential clinical relevance of physiologically informed low-dose iron supplementation strategies in women with iron deficiency.