title: Cofortification of ferric pyrophosphate and citric acid/trisodium citrate into extruded rice grains doubles iron bioavailability through in situ generation of soluble ferric pyrophosphate citrate complexes.
abstract: BACKGROUND
  Iron fortification of rice is a promising strategy for improving iron nutrition. However, it is technically challenging because rice is consumed as intact grains, and ferric pyrophosphate (FePP), which is usually used for rice fortification, has low bioavailability.
  
  
  OBJECTIVE
  We investigated whether the addition of a citric acid/trisodium citrate (CA/TSC) mixture before extrusion increases iron absorption in humans from FePP-fortified extruded rice grains.
  
  
  METHODS
  We conducted an iron absorption study in iron-sufficient young women (n = 20), in which each participant consumed 4 different meals (4 mg Fe/meal): 1) extruded FePP-fortified rice (No CA/TSC); 2) extruded FePP-fortified rice with CA/TSC added before extrusion (CA/TSC extruded); 3) extruded FePP-fortified rice with CA/TSC solution added after cooking and before consumption (CA/TSC solution); and 4) nonextruded rice fortified with a FeSO4 solution added after cooking and before consumption (reference). Iron absorption was calculated from erythrocyte incorporation of stable iron isotopes 14 d after administration. In in vitro experiments, we assessed the soluble and dialyzable iron from rice meals in which CA/TSC was added at different preparation stages and from meals with different iron:CA:TSC ratios.
  
  
  RESULTS
  Fractional iron absorption was significantly higher from CA/TSC-extruded meals (3.2%) than from No CA/TSC (1.7%) and CA/TSC solution (1.7%; all P < 0.05) and was not different from the FeSO4 reference meal (3.4%). In vitro solubility and dialyzability were higher in CA/TSC-extruded rice than in rice with No CA/TSC and CA/TSC solution, and solubility increased with higher amounts of added CA and TSC in extruded rice.
  
  
  CONCLUSIONS
  Iron bioavailability nearly doubled when CA/TSC was extruded with FePP into fortified rice, resulting in iron bioavailability comparable to that of FeSO4 We attribute this effect to an in situ generation of soluble FePP citrate moieties during extrusion and/or cooking because of the close physical proximity of FePP and CA/TSC in the extruded rice matrix. This trial was registered at clinicaltrials.gov as NCT02176759.
authors.affiliation: Laboratories for Human Nutrition and laura.hackl@hest.ethz.ch.
authors.forename: Laura
authors.identifier: http://orcid.org/0000-0002-2645-1200
authors.initials: L
authors.lastname: Hackl
authors.affiliation: Laboratories for Human Nutrition and.
authors.forename: Colin I
authors.initials: CI
authors.lastname: Cercamondi
authors.affiliation: Laboratories for Human Nutrition and.
authors.forename: Christophe
authors.initials: C
authors.lastname: Zeder
authors.affiliation: Laboratories for Human Nutrition and.
authors.forename: Daniela
authors.initials: D
authors.lastname: Wild
authors.affiliation: Food and Soft Materials, Institute of Food, Nutrition and Health, Swiss Federal Institute of Technology Zürich, Zürich, Switzerland.
authors.forename: Horst
authors.initials: H
authors.lastname: Adelmann
authors.affiliation: Laboratories for Human Nutrition and.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Zimmermann
authors.affiliation: Laboratories for Human Nutrition and.
authors.forename: Diego
authors.identifier: http://orcid.org/0000-0002-7366-2182
authors.initials: D
authors.lastname: Moretti
mesh_terms: D000293:Adolescent; D000328:Adult; D001682:Biological Availability; D015992:Body Mass Index; D001835:Body Weight; D002097:C-Reactive Protein / Q000378:metabolism; D002951:Citrates / Q000008:administration & dosage / Q000032:analysis*; D019343:Citric Acid / Q000008:administration & dosage / Q000032:analysis*; D003296:Cooking; D018592:Cross-Over Studies; D011756:Diphosphates / Q000008:administration & dosage / Q000032:analysis*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005527:Food, Fortified; D006801:Humans; D007501:Iron / Q000008:administration & dosage / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D019266:Iron, Dietary / Q000008:administration & dosage; D009752:Nutritional Status; D012275:Oryza / Q000737:chemistry*; D016037:Single-Blind Method; D055815:Young Adult
chemical_list: D002951:Citrates; D011756:Diphosphates; D019266:Iron, Dietary; C514290:trisodium citrate; D019343:Citric Acid; D002097:C-Reactive Protein; D007501:Iron; C049051:ferric pyrophosphate
keywords: extruded rice; ferric pyrophosphate; iron bioavailability; iron deficiency; iron fortification; trisodium citrate