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      Dietary strategies for improving iron status: balancing safety and efficacy

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          Abstract

          In light of evidence that high-dose iron supplements lead to a range of adverse events in low-income settings, the safety and efficacy of lower doses of iron provided through biological or industrial fortification of foodstuffs is reviewed. First, strategies for point-of-manufacture chemical fortification are compared with biofortification achieved through plant breeding. Recent insights into the mechanisms of human iron absorption and regulation, the mechanisms by which iron can promote malaria and bacterial infections, and the role of iron in modifying the gut microbiota are summarized. There is strong evidence that supplemental iron given in nonphysiological amounts can increase the risk of bacterial and protozoal infections (especially malaria), but the use of lower quantities of iron provided within a food matrix, ie, fortified food, should be safer in most cases and represents a more logical strategy for a sustained reduction of the risk of deficiency by providing the best balance of risk and benefits. Further research into iron compounds that would minimize the availability of unabsorbed iron to the gut microbiota is warranted.

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          Iron and cancer: more ore to be mined.

          Iron is an essential nutrient that facilitates cell proliferation and growth. However, iron also has the capacity to engage in redox cycling and free radical formation. Therefore, iron can contribute to both tumour initiation and tumour growth; recent work has also shown that iron has a role in the tumour microenvironment and in metastasis. Pathways of iron acquisition, efflux, storage and regulation are all perturbed in cancer, suggesting that reprogramming of iron metabolism is a central aspect of tumour cell survival. Signalling through hypoxia-inducible factor (HIF) and WNT pathways may contribute to altered iron metabolism in cancer. Targeting iron metabolic pathways may provide new tools for cancer prognosis and therapy.
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            Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting: community-based, randomised, placebo-controlled trial.

            Anaemia caused by iron deficiency is common in children younger than age 5 years in eastern Africa. However, there is concern that universal supplementation of children with iron and folic acid in areas of high malaria transmission might be harmful. We did a randomised, placebo-controlled trial, of children aged 1-35 months and living in Pemba, Zanzibar. We assigned children to daily oral supplementation with: iron (12.5 mg) and folic acid (50 mug; n=7950), iron, folic acid, and zinc (n=8120), or placebo (n=8006); children aged 1-11 months received half the dose. Our primary endpoints were all-cause mortality and admission to hospital. Analyses were by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN59549825. The iron and folic acid-containing groups of the trial were stopped early on Aug 19, 2003, on the recommendation of the data and safety monitoring board. To this date, 24 076 children contributed a follow-up of 25,524 child-years. Those who received iron and folic acid with or without zinc were 12% (95% CI 2-23, p=0.02) more likely to die or need treatment in hospital for an adverse event and 11% (1-23%, p=0.03) more likely to be admitted to hospital; there were also 15% (-7 to 41, p=0.19) more deaths in these groups. Routine supplementation with iron and folic acid in preschool children in a population with high rates of malaria can result in an increased risk of severe illness and death. In the presence of an active programme to detect and treat malaria and other infections, iron-deficient and anaemic children can benefit from supplementation. However, supplementation of those who are not iron deficient might be harmful. As such, current guidelines for universal supplementation with iron and folic acid should be revised.
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              Gut microbiome-host interactions in health and disease

              The gut microbiome is the term given to describe the vast collection of symbiotic microorganisms in the human gastrointestinal system and their collective interacting genomes. Recent studies have suggested that the gut microbiome performs numerous important biochemical functions for the host, and disorders of the microbiome are associated with many and diverse human disease processes. Systems biology approaches based on next generation 'omics' technologies are now able to describe the gut microbiome at a detailed genetic and functional (transcriptomic, proteomic and metabolic) level, providing new insights into the importance of the gut microbiome in human health, and they are able to map microbiome variability between species, individuals and populations. This has established the importance of the gut microbiome in the disease pathogenesis for numerous systemic disease states, such as obesity and cardiovascular disease, and in intestinal conditions, such as inflammatory bowel disease. Thus, understanding microbiome activity is essential to the development of future personalized strategies of healthcare, as well as potentially providing new targets for drug development. Here, we review recent metagenomic and metabonomic approaches that have enabled advances in understanding gut microbiome activity in relation to human health, and gut microbial modulation for the treatment of disease. We also describe possible avenues of research in this rapidly growing field with respect to future personalized healthcare strategies.
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                Author and article information

                Journal
                Nutr Rev
                Nutr. Rev
                nutritionreviews
                nutritionreviews
                Nutrition Reviews
                Oxford University Press
                0029-6643
                1753-4887
                January 2017
                13 December 2016
                13 December 2016
                : 75
                : 1
                : 49-60
                Affiliations
                A.M. Prentice, D. Pereira, C. Cerami, and R. Wegmuller are with the Medical Research Council (MRC) Unit The Gambia, Fajara, Banjul, The Gambia. A.M. Prentice and R. Wegmuller are with the MRC International Nutrition Group, London School of Hygiene & Tropical Medicine, London, United Kingdom. Y.A. Mendoza, A. Constable, and J. Spieldenner are with the Nestlé Research Centre, Lausanne, Switzerland. D. Pereira is with the Department of Pathology, University of Cambridge, Cambridge, United Kingdom. C. Cerami is with the Division of Infectious Diseases, Institute for Global Health & Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
                Author notes
                A.M. Prentice, MRC Unit The Gambia, PO Box 273, Atlantic Road, Fajara, The Gambia. Email: aprentice@ 123456mrc.gm . Phone: +220-7236903.
                Article
                nuw055
                10.1093/nutrit/nuw055
                5155616
                27974599
                66c9e481-a982-475e-8140-2217884672f5
                © The Author(s) 2016. Published by Oxford University Press on behalf of the International Life Sciences Institute.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Page count
                Pages: 12
                Categories
                Special Articles

                Nutrition & Dietetics
                food fortification,iron,safety,staple foods,supplementation.
                Nutrition & Dietetics
                food fortification, iron, safety, staple foods, supplementation.

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