Reduced-dose alternate-day oral iron supplementation in women with iron deficiency: a randomized controlled trial
In brief
Alternate-day iron raised ferritin as much as daily dosing in a small trial
In 66 women with iron deficiency, 21 mg of iron every 48 hours increased ferritin over 42 days about as much as 30 mg daily, despite lower total iron exposure. Other iron measures also improved in both groups, while hemoglobin stayed stable and side effects were mild; the short trial leaves longer-term effectiveness and tolerability uncertain.
- Journal
- European journal of nutrition (Q1)
- Published
- 25 October 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Maria Chiara Valerii, Nikolas Kostantine Dussias, Anna Perri, Renato Spigarelli, Alberto Bernacchi, Fernando Rizzello, et al.
- PMID
- 42927507
- DOI
- 10.1007/s00394-026-04139-9
Why clinicians should know about it
- Picked for Hematology (top studies of the week, 8 November 2026): Randomized trial of oral iron for iron deficiency
Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.