Effect of iron-fortified foods on hematologic and biological outcomes: systematic review of randomized controlled trials 1–4 Tarun Gera, Harshpal Singh Sachdev, and Erick Boy ABSTRACT Background: The utility of iron fortification of food to improve iron deficiency, anemia, and biological outcomes is not proven un- equivocally. Objectives: The objectives were to evaluate 1) the effect of iron fortification on hemoglobin and serum ferritin and the prevalence of iron deficiency and anemia, 2) the possible predictors of a pos- itive hemoglobin response, 3) the effect of iron fortification on zinc and iron status, and 4) the effect of iron-fortified foods on mental and motor development, anthropometric measures, and infections. Design: Randomized and pseudorandomized controlled trials that included food fortification or biofortification with iron were included. Results: Data from 60 trials showed that iron fortification of foods resulted in a significant increase in hemoglobin (0.42 g/dL; 95% CI: 0.28, 0.56; P , 0.001) and serum ferritin (1.36 lg/L; 95% CI: 1.23, 1.52; P , 0.001), a reduced risk of anemia (RR: 0.59; 95% CI: 0.48, 0.71; P , 0.001) and iron deficiency (RR: 0.48; 95% CI: 0.38, 0.62; P , 0.001), improvement in other indicators of iron nutriture, and no effect on serum zinc concentrations, infections, physical growth, and mental and motor development. Significant heterogeneity was observed for most of the evaluated outcomes. Sensitivity analyses and meta-regression for hemoglobin suggested a higher response with lower trial quality (suboptimal allocation concealment and blinding), use of condiments, and sodium iron edetate and a lower response when adults were included. Conclusion: Consumption of iron-fortified foods results in an im- provement in hemoglobin, serum ferritin, and iron nutriture and a reduced risk of remaining anemic and iron deficient. Am J Clin Nutr 2012;96:309–24. INTRODUCTION Iron deficiency anemia is a widespread problem with health and economic consequences, such as poor cognitive development in children, lower worker productivity, and increased maternal mortality (1, 2). Anemia affects nearly one-third of the world’s population, primarily infants and young children from de- veloping countries (3–5). Dietary strategies to counter anemia include iron supple- mentation, food fortification, or dietary modification. Food for- tification is often propagated as the most realistic way to increase iron intake on a widespread and sustainable basis and is currently implemented in the United States, Britain, and most of Latin America, among other locations. Currently, biofortification of crops is also being intensively evaluated as a more sustainable and complementary alternative to food fortification. Hemoglobin and ferritin are currently considered the most efficient indicators of population response to iron interventions (6). Relevant randomized controlled trials provide conflicting evidence regarding the utility of iron-fortified foods in improving the iron status and reducing anemia in populations (7–9). A recent systematic review of randomized controlled trials in children documented that iron-fortified foods resulted in a substantially lower average hemoglobin response in comparison with oral medicinal iron supplementation (0.25 compared with 0.74 g/dL) (7). The success of iron-fortified food interventions depends on several factors, including the consumption pattern of the fortified food, effect of the fortificants on the taste and appearance of the food vehicle, shelf life of the fortified food, bioavailability of the iron fortificants, and the baseline iron status of the population (10, 11), which need greater evaluation for the success of this strategy. A new dimension has been added with the emergence of zinc as an important micronutrient for child health (12). Iron and zinc deficiencies frequently coexist in populations that consume diets with insufficient animal-source foods (13). Iron and zinc have been thought to compete for absorptive pathways at the enter- ocyte level (14). It is, therefore, important to determine how iron fortification of foods affects zinc deficiency, particularly in vegetarian populations subsisting on borderline zinc nutriture. Policy makers, program implementers, and the target pop- ulation need to carefully weigh the benefits and safety of food fortification and biofortification with iron before recommend- ing them for populations. The current systematic review was therefore conducted to evaluate 1) the effect of iron-fortified foods and biofortified crops on hemoglobin and serum ferritin and the prevalence of iron deficiency and anemia and other 1 From the S.L. Jain Hospital, Delhi, India (TG); the Sitaram Bhartia Institute of Science and Research, New Delhi, India (HSS); and the Inter- national Food Policy Research Institute, Washington, DC (EB). 2 Protocol available from http://www.harvestplus.org/content/iron-fortified- foods-protocol. 3 Supported by research agreement no. 2006X053SAC from the Interna- tional Food Policy Research Institute, 2033 K Street, NW Washington, DC 20006. Time support was provided by the Sitaram Bhartia Institute of Sci- ence and Research, New Delhi, India (to HSS). 4 Address correspondence and reprint requests to HS Sachdev, E-6/12 Vasant Vihar, New Delhi 110057, India. E-mail: hpssachdev@gmail.com. Received December 12, 2011. Accepted for publication April 13, 2012. First published online July 3, 2012; doi: 10.3945/ajcn.111.031500. Am J Clin Nutr 2012;96:309–24. Printed in USA. Ó 2012 American Society for Nutrition 309 by guest on February 6, 2016 ajcn.nutrition.org Downloaded from 31500.DC1.html http://ajcn.nutrition.org/content/suppl/2012/07/31/ajcn.111.0 Supplemental Material can be found at: