Oral iron therapy with iron maltol versus ferrous sulphate in inflammatory bowel disease: Intra-individual comparison indicates level pegging on increase in plasma hepcidin levels

Background Current anemia guidelines for patients with inflammatory bowel disease (IBD) recommend oral rather than intravenous iron therapy unless patients have severe anemia, active inflammation or intolerance to oral iron (OI). In IBD, OI causes gastrointestinal side-effects and absorption is often poor. Moreover, OI supplements induce an increase in plasma hepcidin (pHep) that persists for 24h and impairs iron absorption from same-day/next-day doses.

Aims We compared changes in pHep levels for 4h following intake of ferrous vs. ferric OI and considered implications for OI dosing.

Methods A comparative, single-center, open clinical crossover trial was conducted. Anemia was defined per WHO definitions, iron deficiency (ID) as ferritin<100 mg/L, CRP≥5mg/L and Hb>WHO cut-offs. Plasma CRP≥5mg/dL defined inflammation. Patients took 2 OI absorption tests 2 weeks apart: at the 1st visit, with iron(II)-glycine-sulfate complex (Ferro sanol®​, FeSulf) and at the 2nd visit, with iron(III)-maltol (Feraccru®​, IM), or vice-versa. Oral absorption tests took place a.m. after overnight fasting. Patients took a 30mg iron tablet and blood was drawn after 60 & 120min. After a very low-iron lunch (potato soup, bread) the protocol was repeated. AUC for iron absorption was calculated for 60 & 120min from a.m. & p.m. baselines. Blood samples were analyzed by LC/MS/MS (Immundiagnostik, Bensheim).

Results Of 23 IBD patients enrolled (12f/11m;11CD/12UC;45.1±14.7y), 7(30.4%) had inflammation. After the 1st OI dose, plasma iron increased significantly vs. baseline in both feSulf and IM groups (p<0.001), regardless of inflammation. After the 2nd (p.m.) dose, plasma iron increased slightly for IM (p=0.538) and decreased significantly for feSulf (p=0.011). Iron absorption capacity a.m. (p=0.644) and p.m. (p=0.280) did not statistically differ for IM vs. feSulf. In both groups, pHep values were significantly increased at p.m. baseline prior to the 2nd iron dose (p<0.001). Whereas a.m., pHep levels correlated negatively with iron absorption capacity independent of inflammatory status (-0.408, p<0.05), p.m. both groups showed no increase in plasma iron (-0.253, p=0.130).

Conclusion pHep levels increased after both fSulf and IM, thus impairing iron absorption of the 2nd daily dose. In IDA, OI supplements of both ferric(III) and ferrous(II) iron cause an acute pHep increase for 24h, even if hepatic Hep expression is suppressed by ID and erythropoietic drive. Alternate day dosing of OI supplements seems preferable.

Publication History

Article published online:
19 August 2022