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Supplementing iron and zinc: double blind, randomized evaluation of separate or combined delivery



Many children have diets deficient in both iron and zinc, but there has been some evidence of negative interactions when they are supplemented together. The optimal delivery approach would maximize clinical benefits of both nutrients. We studied the effectiveness of different iron and zinc supplement delivery approaches to improve diarrhea and anemia in a rural Bangladesh population.

Study Design:

Randomized, double blind, placebo-controlled factorial community trial.


Iron supplementation alone increased diarrhea, but adding zinc, separately or together, attenuated these harmful effects. Combined zinc and iron was as effective as iron alone for iron outcomes. All supplements were vomited <1% of the time, but combined iron and zinc were vomited significantly more than any of the other supplements. Children receiving zinc and iron (together or separately) had fewer hospitalizations. Separating delivery of iron and zinc may have some additional benefit in stunted children.


Separate and combined administration of iron and zinc are equally effective for reducing diarrhea, hospitalizations and improving iron outcomes. There may be some benefit in separate administration in stunted children.

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  • Baqui AH, Zaman K, Persson LA, El Arifeen S, Yunus M, Begum N et al. (2003). Simultaneous weekly supplementation of iron and zinc is associated with lower morbidity due to diarrhea and acute lower respiratory infection in Bangladeshi infants. J Nutr 133, 4150–4157.

    CAS  Article  Google Scholar 

  • Berger J, Ninh NX, Khan NC, Nhien NV, Lien DK, Trung NQ et al. (2006). Efficacy of combined iron and zinc supplementation on micronutrient status and growth in Vietnamese infants. Eur J Clin Nutr 60, 443–454.

    CAS  Article  Google Scholar 

  • Bhutta ZA, Black RE, Brown KH, Gardner JM, Gore S, Hidayat A et al. (1999). Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: pooled analysis of randomized clinical trials. J Pediatr 135, 689–697.

    CAS  Article  Google Scholar 

  • Booth IW, Aukett MA (1997). Iron deficiency anemia in infancy early childhood. Arch Dis Child 76, 549–553.

    CAS  Article  Google Scholar 

  • Brown KH, Peerson JM, Rivera J, Allen LH (2002). Effect of supplemental zinc on the growth and serum zinc concentrations of prepubertal children: a meta-analysis of randomized controlled trials. Am J Clin Nutr 75, 1062–1071.

    CAS  Article  Google Scholar 

  • Castillo-Duran C, Vial P (1988). Trace mineral balance during acute diarrhea in infants. J Pediatr 113, 452–457.

    CAS  Article  Google Scholar 

  • de Andraca I, Casillo M, Walter T (1997). Psychomotor development and behavior in iron-deficient anemic infants. Nutr Rev 55, 125–132.

    CAS  Article  Google Scholar 

  • de Benoist B, Darnton-Hill I, Lynch S, Allen L, Savioli L (2006). Zinc and iron supplementation trials in Nepal and Tanzania. Lancet 367, 816.

    Article  Google Scholar 

  • English M, Snow RW (2006). Iron and folic acid supplementation and malaria risk. Lancet 367, 90–91.

    Article  Google Scholar 

  • Fischer Walker C, Kordas K, Stoltzfus RJ, Black RE (2005). Interactive effects of iron and zinc on biochemical and functional outcomes in supplementation trials. Am J Clin Nutr 82, 5–12.

    Article  Google Scholar 

  • Gera T, Sachdev HP (2002). Effect of iron supplementation on incidence of infectious illness in children: systematic review. BMJ 325, 1142.

    CAS  Article  Google Scholar 

  • Gibson RS (1994). Zinc nutrition in developing countries. Nutr Res Rev 7, 151–173.

    CAS  Article  Google Scholar 

  • Iannotti LL, Tielsch JM, Black MM, Black RE (2006). Iron supplementation in early childhood: health benefits and risks. Am J Clin Nutr 84, 1261–1276.

    CAS  Article  Google Scholar 

  • Lind T, Lönnerdal B, Stenlund H, Ismail D, Seswandhana R, Ekström EC et al. (2003). A community-based randomized controlled trial of iron and zinc supplementation in Indonesian infants: interactions between iron and zinc. Am J Clin Nutr 77, 883–890.

    CAS  Article  Google Scholar 

  • Lind T, Lönnerdal B, Stenlund H, Gamayanti IL, Ismail D, Seswandhana R et al. (2004). A community-based randomized controlled trial of iron and zinc supplementation in Indonesian infants: effects on growth and development. Am J Clin Nutr 80, 729–736.

    CAS  Article  Google Scholar 

  • Sazawal S, Black RE, Ramsan M, Chwaya HM, Stoltzfus RJ, Dutta A et al. (2006). 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. Lancet 367, 133–143.

    CAS  Article  Google Scholar 

  • Sazawal S, Black RE, Menon VP, Dinghra P, Caulfield LE, Dhingra U et al. (2001). Zinc supplementation in infants born small for gestational age reduces mortality: a prospective, randomized, controlled trial. Pediatrics 108, 1280–1286.

    CAS  Article  Google Scholar 

  • Tielsch JM, Khatry SK, Stoltzfus RJ, Katz J, LeClerq SC, Adhikari R et al. (2006). Effect of routine prophylactic supplementation with iron and folic acid on preschool child mortality in southern Nepal: community-based, cluster-randomised, placebo-controlled trial. Lancet 367, 144–152.

    CAS  Article  Google Scholar 

  • UNICEF (2001). The State of the World's Children. UNICEF Publications: New York.

  • Wieringa FT, Berger J, Dijkhuizen MA, Hidayat A, Ninh NX, Utomo B et al. (2007). Combined iron and zinc supplementation in infants improved iron and zinc status, but interactions reduced efficacy in a multicountry trial in southeast Asia. J Nutr 137, 466–471.

    CAS  Article  Google Scholar 

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This study was funded by the US Agency for International Development through the Global Research Activity award #HRN-A-00-96-90006-00 to the Johns Hopkins Bloomberg School of Public Health. We thank Saifuddin Ahmed (Johns Hopkins Bloomberg School of Public Health) and Parivash Nourjah (Johns Hopkins Medical Institutions, Agency for Healthcare Research and Quality) for their statistical assistance, Hervé-Pierre Le Goascoz (Nutriset) and Neal Brandes (USAID) for their assistance and support through this project, and most of all the entire ICDDR,B team, the Kumudini hospital staff, and the Mirzapur community.

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Correspondence to S Chang.

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Contributors: SC, AB, RB, SA, MW, KZ contributed to study design. SA, SB, MW, KMR, TR, AM, NB contributed to collection of data. SC, RB contributed to analysis of data. SC prepared the first draft of the manuscript. All authors provided significant advice, contributed to, and approved the final manuscript.This study was registered in (identifier number NCT00470158), and approved by the Johns Hopkins Bloomberg School of Public Health Institutional Review Board (H. and the International Centre for Diarrhoeal Disease Research, Bangladesh Ethical Review Committee (2005-040).


The findings and conclusions in this document are those of the authors, who are responsible for its contents; the findings and conclusions do not necessarily represent the views of AHRQ or USAID. Therefore, no statement in this report should be construed as an official position of these entities, the US Department of Health and Human Services, or the US Agency for International Development.

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Chang, S., El Arifeen, S., Bari, S. et al. Supplementing iron and zinc: double blind, randomized evaluation of separate or combined delivery. Eur J Clin Nutr 64, 153–160 (2010).

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  • iron
  • zinc
  • supplement
  • delivery
  • interaction
  • diarrhea

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