Iron deficiency anemia: A comprehensive review on iron absorption, bioavailability and emerging food fortification approaches

The most widespread dietary problem in the world is mineral deficiency. We used the nicotianamine synthase (NAS) gene to increase mineral contents in rice grains. Nicotianamine (NA) is a chelator of metals and a key component of metal homeostasis. We isolated activation-tagged mutant lines in which expression of a rice NAS gene, OsNAS3, was increased by introducing 35S enhancer elements. Shoots and roots of the OsNAS3 activation-tagged plants (OsNAS3-D1) accumulated more Fe and Zn. Seeds from our OsNAS3-D1 plants grown on a paddy field contained elevated amounts of Fe (2.9-fold), Zn (2.2-fold), and Cu (1.7-fold). The NA level was increased 9.6-fold in OsNAS3-D1 seeds. Analysis by size exclusion chromatography coupled with inductively coupled plasma mass spectroscopy showed that WT and OsNAS3-D1 seeds contained equal amounts of Fe bound to IP6, whereas OsNAS3-D1 had 7-fold more Fe bound to a low molecular mass, which was likely NA. Furthermore, this activation led to increased tolerance to Fe and Zn deficiencies and to excess metal (Zn, Cu, and Ni) toxicities. In contrast, disruption of OsNAS3 caused an opposite phenotype. To test the bioavailability of Fe, we fed anemic mice with either engineered or WT seeds for 4 weeks and measured their concentrations of hemoglobin and hematocrit. Mice fed with engineered seeds recovered to normal levels of hemoglobin and hematocrit within 2 weeks, whereas those that ate WT seeds remained anemic. Our results suggest that an increase in bioavailable mineral content in rice grains can be achieved by enhancing NAS expression.

Based on many cell culture, animal and human studies, it is well known that the most challenge issue for developing polyphenolics as chemoprevention or anti-diabtetic agents is the low oral bioavailability, which may be the major reason relating to its ambiguous therapeutic effects and large inter-individual variations in clinical trials. This review intends to highlight the unscientific evaluation on the basis of the published data regarding in vitro bioactivity of polyphenols, which may sometimes mislead the researchers and to conclude that: first, bio-accessibilities values obtained in the studies for polyphenols should be highly reconsidered in accordance with the abundant newly identified circulating and excreted metabolites, with a particular attention to colonic metabolic products which are obviously contributing much more than expected to their absorptions; second, it is phenolic metabolites, which are formed in the small intestine and hepatic cells,low molecular weight catabolic products of the colonic microflora to travel around the human body in the circulatory system or reach body tissues to elicit bioactive effects. It is concluded that better performed in vivo intervention and in vitro mechanistic studies are needed to fully understand how these molecules interact with human physiological and pathological processes.