Mechanisms of Iron Uptake from Ferric Phosphate Nanoparticles in Human Intestinal Caco-2 Cells.

Antonio Perfecto,Paul Sharp,Christine Elgy,Susan Fairweather-Tait,Eugenia Valsami-Jones,Florentine Hilty

doi:10.3390/nu9040359

Abstract

Food fortification programs to reduce iron deficiency anemia require bioavailable forms of iron that do not cause adverse organoleptic effects. Rodent studies show that nano-sized ferric phosphate (NP-FePO4) is as bioavailable as ferrous sulfate, but there is controversy over the mechanism of absorption. We undertook in vitro studies to examine this using a Caco-2 cell model and simulated gastrointestinal (GI) digestion. Supernatant iron concentrations increased inversely with pH, and iron uptake into Caco-2 cells was 2–3 fold higher when NP-FePO4 was digested at pH 1 compared to pH 2. The size and distribution of NP-FePO4 particles during GI digestion was examined using transmission electron microscopy. The d50 of the particle distribution was 413 nm. Using disc centrifugal sedimentation, a high degree of agglomeration in NP-FePO4 following simulated GI digestion was observed, with only 20% of the particles ≤1000 nm. In Caco-2 cells, divalent metal transporter-1 (DMT1) and endocytosis inhibitors demonstrated that NP-FePO4 was mainly absorbed via DMT1. Small particles may be absorbed by clathrin-mediated endocytosis and micropinocytosis. These findings should be considered when assessing the potential of iron nanoparticles for food fortification.

Highlights

Iron deficiency is the most prevalent nutritional deficiency in the world, affecting 1–2 billion people worldwide [1]
Our experiments demonstrate that iron uptake from NP-FePO4 occurred predominately through increased iron in the supernatant fraction and entry via the divalent metal transporter-1 (DMT1) transporter in the Caco-2 cell model
Some NP-FePO4 (200) may be absorbed intact in Caco-2 cells independently from DMT1, but most likely this mechanism has a minor role in iron uptake

Summary

Introduction

Iron deficiency is the most prevalent nutritional deficiency in the world, affecting 1–2 billion people worldwide [1]. Iron chelates, and elemental powders are all iron sources approved for food fortification [3], but each form has inherent disadvantages. Soluble iron compounds, such as ferrous sulfate (FeSO4 ) and ferrous gluconate, have high iron bioavailability but may cause adverse organoleptic changes when added to foods. Insoluble iron compounds, such as electrolytic iron and ferric phosphate (FePO4 ), are stable in foods but have low iron bioavailability [4,5,6]. FePO4 is an iron compound that causes no adverse organoleptic changes in food matrices, but is poorly absorbed (25%)

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