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Food fortification with iron nanoparticles (NPs) could help prevent iron deficiency anemia, but the absorption pathway and biodistribution of iron-NPs and their bioavailability in humans is unclear. Dietary non-heme iron is physiologically absorbed via the divalent metal transporter-1 (DMT1) pathway. Using radio- iron isotope labelling in mice with a partial knockdown of intestine-specific DMT1, we assessed oral absorption and tissue biodistribution of nanostructured ferric phosphate (FePO 4 -NP; specific surface area [SSA] 98 m 2 g -1 ) compared to to ferrous sulfate (FeSO 4 ), the reference compound. We show that absorption of iron from FePO 4 -NP appears to be largely DMT1 dependent and that its biodistribution after absorption is similar to that from FeSO 4 , without abnormal deposition of iron in the reticuloendothelial system. Furthermore, we demonstrate high bioavailability from iron NPs in iron deficient anemic women in a randomized, cross-over study using stable-isotope labelling: absorption and subsequent erythrocyte iron utilization from two  57 Fe-labeled FePO 4 -NP with SSAs of 98 m 2 g −1  and 188 m 2 g −1  was 2.8-fold and 5.4-fold higher than from bulk FePO 4  with an SSA of 25 m 2 g −1  ( P  &lt; 0.001) when added to a rice and vegetable meal consumed by iron deficient anemic women. The FePO 4 -NP 188 m 2 g -1  achieved 72% relative bioavailability compared to FeSO 4 . These data suggest FePO 4 -NPs may be useful for nutritional applications.

Iron from nanostructured ferric phosphate: absorption and biodistribution in mice and bioavailability in iron deficient anemic women