title: Nanoparticulate iron(III) oxo-hydroxide delivers safe iron that is well absorbed and utilised in humans.
abstract: Iron deficiency is the most common nutritional disorder worldwide with substantial impact on health and economy. Current treatments predominantly rely on soluble iron which adversely affects the gastrointestinal tract. We have developed organic acid-modified Fe(III) oxo-hydroxide nanomaterials, here termed nano Fe(III), as alternative safe iron delivery agents. Nano Fe(III) absorption in humans correlated with serum iron increase (P < 0.0001) and direct in vitro cellular uptake (P = 0.001), but not with gastric solubility. The most promising preparation (iron hydroxide adipate tartrate: IHAT) showed ~80% relative bioavailability to Fe(II) sulfate in humans and, in a rodent model, IHAT was equivalent to Fe(II) sulfate at repleting haemoglobin. Furthermore, IHAT did not accumulate in the intestinal mucosa and, unlike Fe(II) sulfate, promoted a beneficial microbiota. In cellular models, IHAT was 14-fold less toxic than Fe(II) sulfate/ascorbate. Nano Fe(III) manifests minimal acute intestinal toxicity in cellular and murine models and shows efficacy at treating iron deficiency anaemia.
  
  
  BACKGROUND
  This paper reports the development of novel nano-Fe(III) formulations, with the goal of achieving a magnitude less intestinal toxicity and excellent bioavailability in the treatment of iron deficiency anemia. Out of the tested preparations, iron hydroxide adipate tartrate met the above criteria, and may become an important tool in addressing this common condition.
authors.affiliation: MRC Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, United Kingdom. Electronic address: dora.pereira@mrc-hnr.cam.ac.uk.
authors.forename: Dora I A
authors.initials: DI
authors.lastname: Pereira
authors.affiliation: MRC Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, United Kingdom.
authors.forename: Sylvaine F A
authors.initials: SF
authors.lastname: Bruggraber
authors.affiliation: MRC Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, United Kingdom.
authors.forename: Nuno
authors.initials: N
authors.lastname: Faria
authors.affiliation: MRC Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, United Kingdom.
authors.forename: Lynsey K
authors.initials: LK
authors.lastname: Poots
authors.affiliation: Department of Nutritional Science and Toxicology, University of California, Berkeley, CA, USA.
authors.forename: Mani A
authors.initials: MA
authors.lastname: Tagmount
authors.affiliation: MRC Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, United Kingdom.
authors.forename: Mohamad F
authors.initials: MF
authors.lastname: Aslam
authors.affiliation: Iron Metabolism Laboratory, QIMR Berghofer Medical Research Institute, PO Royal Brisbane Hospital, Brisbane, Australia.
authors.forename: David M
authors.initials: DM
authors.lastname: Frazer
authors.affiliation: Department of Nutritional Science and Toxicology, University of California, Berkeley, CA, USA.
authors.forename: Chris D
authors.initials: CD
authors.lastname: Vulpe
authors.affiliation: Iron Metabolism Laboratory, QIMR Berghofer Medical Research Institute, PO Royal Brisbane Hospital, Brisbane, Australia.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Anderson
authors.affiliation: MRC Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, United Kingdom.
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Powell
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000188:drug therapy*; D000818:Animals; D018938:Caco-2 Cells; D002470:Cell Survival; D005290:Ferric Compounds / Q000737:chemistry* / Q000627:therapeutic use*; D019073:HT29 Cells; D006801:Humans; D007408:Intestinal Absorption; D007501:Iron / Q000378:metabolism; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D051381:Rats
chemical_list: D005290:Ferric Compounds; D007501:Iron
keywords: Bioavailability; Iron supplementation; Ligand-modified Fe(III) poly oxo-hydroxide; Microbiota; Redox damage