Ferric Pyrophosphate Forms Soluble Iron Coordination Complexes with Zinc Compounds and Solubilizing Agents in Extruded Rice and Predicts Increased Iron Solubility and Bioavailability in Young Women

Abstract

Background: Co-extrusion of ferric pyrophosphate (FePP) with solubilizers, citric acid/trisodium citrate (CA/TSC), or ethylenediaminetetraacetic acid (EDTA) sharply increases iron absorption. Whether this can protect against the inhibition of iron absorption by phytic acid (PA) is unclear. Sodium pyrophosphate (NaPP) may be a new enhancer of iron absorption from FePP.

Objectives: Our objectives were to 1) investigate the ligand coordination of iron, zinc, and solubilizers in extruded rice and test associations with iron solubility and absorption, 2) assess whether co-extrusion of FePP + CA/TSC rice can protect against inhibition of iron absorption by PA; 3) determine the effect of zinc oxide (ZnO) compared with zinc sulfate (ZnSO₄), and 4) quantify iron absorption from FePP + NaPP rice.

Methods: We produced labeled ⁵⁷FePP rice cofortified with ZnSO₄ and EDTA, CA/TSC or NaPP, and FePP + EDTA rice with ZnO. We used electron paramagnetic resonance (EPR) to characterize iron-ligand complexes. We measured in vitro iron solubility and fractional iron absorption (FIA) in young women (n = 21, age: 22 ± 2 y, BMI: 21.3 ± 1.5 kg/m² geometric mean plasma ferritin, 28.5 μg/L) compared with ferrous sulfate (⁵⁸FeSO₄). FIA was compared by linear mixed-effect model analysis.

Results: The addition of zinc and solubilizers created new iron coordination complexes of Fe(III) species with a weak ligand field at a high-spin state that correlated with solubility (r² = 0.50, P = 0.02) and absorption (r² = 0.72, P = 0.02). Phytic acid reduced FIA from FePP + CA/TSC rice by 50% (P < 0.001), to the same extent as FeSO₄. FIA from FePP + EDTA + ZnO and FePP + EDTA + ZnSO₄ rice did not significantly differ. Mean FIAs from FePP + EDTA + ZnSO₄, FePP + CA/TSC + ZnSO₄, and FePP + NaPP + ZnSO₄ rice were 9% to 11% and did not significantly differ from each other or from FeSO₄.

Conclusion: Rice extrusion of FePP with solubilizers resulted in bioavailable iron coordination complexes. In the case of FePP + CA/TSC, PA exerted similar inhibition of FIA as with FeSO₄. FePP + NaPP could be a further viable solubilizing agent for rice fortification. This study was registered at clinicaltrials.gov as NCT03703739.

Keywords: bioavailability; electron paramagnetic resonance; extrusion; fortification; iron absorption; iron deficiency; rice; solubilizing agent; women.