In light of the evidence that high-dose iron supplements lead to a range of adverse events in low-income settings researchers from the Nutrition Theme at MRC Unit The Gambia (MRCG), assessed the safety and efficacy of lower doses of iron provided through biological or industrial fortification of foodstuffs. Their findings published in Nutrition Reviews suggest the need for further research into iron compounds that would minimize the availability of unabsorbed iron to the gut microbiota. There is strong evidence that supplemental iron given in nonphysiological amounts (ie too high) can increase the risk of bacterial and protozoal infections (especially malaria), but the use of lower quantities of iron provided within a food matrix, i.e., 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.

In this review of the published evidence, strategies for point-of-manufacture chemical fortification were compared with biofortification achieved through plant breeding. Recent insights into the mechanisms of human iron absorption and regulation illustrate mechanisms by which iron can promote malaria and bacterial infections and the role of iron in modifying the gut microbiota.

Several conclusions were arrived at. First, new insights into human iron metabolism, especially those derived from the discovery of the hepcidin/ferroportin system for regulating iron uptake, suggest that the strategy of providing large nonphysiological bolus doses of highly absorbable iron as supplements works against the highly evolved systems for safely maintaining iron homeostasis in humans and hence may be hazardous.

Second, an important cause of iron deficiency is the inflammatory blockade, and any strategy to reduce iron deficiency and iron-deficiency anemia should include interventions to limit infections and inflammation (including low-grade inflammation). If inflammation can be reduced, then elimination of the iron blockade will permit healthy iron homeostasis at lower levels of dietary iron.

Third, chemical or biological fortification of staple foods provides a logical approach as a public health strategy and should be pursued. The data does not support the conclusion that iron-fortified foods are without risk, but any possible risks are probably much lower than those associated with the high burden of disease and reduced functional capacity caused by iron deficiency worldwide. When cost or any other constraint prevents treatment of inflammation or infection, fortification with low doses of iron homogeneously diluted in a larger mass of food remains one of the safest strategies available to reduce the risk of deficiency.

These considerations are important in the context of the United Nations Sustainable Development Goals, since iron-deficiency anemia is a main indicator of micronutrient deficiencies among women of reproductive age and children under the age of 5 years. Future research is required to examine the effects of unabsorbed iron on the gut microbiota. When asked to comment on the conclusions of the findings, Prof Andrew Prentice, Head of the Nutrition Theme said “Fortifying foods with iron, including biofortification achieved by classical plant breeding or GMO techniques, represents a very logical approach to combatting the vast global burden of iron deficiency. There is a lack of specific data comparing the safety of iron supplements versus food fortification but logic dictates that fortification would be a more physiologically acceptable, and hence safer, approach.”

Read more about the findings on the PubMed website on https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5155616/

Authors
Prentice AM, Mendoza YA, Pereira D, Cerami C, Wegmuller R, Constable A, Spieldenner J.

Acknowledgments
Special thanks is extended to the Nestlé Research Centre, Lausanne, Switzerland, Bill & Melinda Gates Foundation, Medical Research Council (MRC) International Nutrition Group, UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement.