Volume 75, Issue 1
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


Iron and zinc deficiencies are common in developing countries and supplementation is one way of reversing these deficiencies. The objective of this randomized, placebo-controlled clinical trial was to identify the effect of daily supplementation with iron, zinc, and iron plus zinc on the morbidity experience of 855 children 0.5–15 years of age in Peru. Single nutrient supplementation with zinc reduced diarrhea morbidity by 23% in all children. In older children (more than five years of age), iron supplementation increased morbidity due to and diarrhea. In younger children, iron combined with zinc provided protection against malaria, but also interfered with some of the diarrhea protection associated with zinc supplementation. No statistically significant effect was observed of either supplement on incidence of respiratory infection or anthropometric indices. Iron and zinc deficiencies should be remedied, and combined supplementation may be a good option, particularly in younger children in malaria-endemic areas, although local endemicity and species-specific prevalence should be considered carefully when designing any supplementation program involving iron in a malaria-endemic area.


Article metrics loading...

The graphs shown below represent data from March 2017
Loading full text...

Full text loading...



  1. Black RE, 2003. Zinc deficiency, infectious disease and mortality in the developing world. J Nutr 133: 1485S–1489S. [Google Scholar]
  2. Grantham-McGregor S, Ani C, 2001. A review of studies on the effect of iron deficiency on cognitive development in children. J Nutr 131: 649S–666S. [Google Scholar]
  3. de Silva A, Atukorala S, Weerasinghe I, Ahluwalia N, 2003. Iron supplementation improves iron status and reduces morbidity in children with or without upper respiratory tract infections: a randomized controlled study in Colombo, Sri Lanka. Am J Clin Nutr 77: 234–241. [Google Scholar]
  4. Idjradinata P, Pollitt E, 1993. Reversal of developmental delays in iron-deficient anaemic infants treated with iron. Lancet 341: 1–4. [Google Scholar]
  5. Beard JL, 2001. Iron biology in immune function, muscle metabolism and neuronal functioning. J Nutr 131: 568S–579S. [Google Scholar]
  6. Shankar AH, 2000. Nutritional modulation of malaria morbidity and mortality. J Infect Dis 182 (Suppl 1): S37–S53. [Google Scholar]
  7. Sazawal S, Black RE, Ramsan M, Chwaya HM, Stoltzfus RJ, Dutta A, Dhingra U, Kabole I, Deb S, Othman MK, Kabole FM, 2006. 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. [Google Scholar]
  8. Shankar AH, Prasad AS, 1998. Zinc and immune function: the biological basis of altered resistance to infection. Am J Clin Nutr 68: 447S–463S. [Google Scholar]
  9. 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. [Google Scholar]
  10. Whittaker P, 1998. Iron and zinc interactions in humans. Am J Clin Nutr 68: 442S–446S. [Google Scholar]
  11. Solomons NW, 1986. Competitive interaction of iron and zinc in the diet: consequences for human nutrition. J Nutr 116: 927–935. [Google Scholar]
  12. Kordas K, Stoltzfus RJ, 2004. New evidence of iron and zinc interplay at the enterocyte and neural tissues. J Nutr 134: 1295–1298. [Google Scholar]
  13. Lind T, Lonnerdal B, Stenlund H, Ismail D, Seswandhana R, Ekstrom EC, Persson LA, 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. [Google Scholar]
  14. Dijkhuizen MA, Wieringa FT, West CE, Martuti S, Muhilal, 2001. Effects of iron and zinc supplementation in Indonesian infants on micronutrient status and growth. J Nutr 131: 2860–2865. [Google Scholar]
  15. Walker CF, 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. [Google Scholar]
  16. International Nutritional Anemia Consultative Group (INACG), 1998. Guidelines for the Use of Iron Supplements to Prevent and Treat Iron Deficiency Anemia. Washington, DC: International Life Sciences Institute.
  17. Tielsch JM, Khatry S, Stoltzfus RJ, Katz J, LeClerq SC, Adhikari R, Mullany LC, Shresta S, Black RE, 2006. 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. [Google Scholar]
  18. Aramburu GJ, Ramal AC, Witzig R, 1999. Malaria reemergence in the Peruvian Amazon region. Emerg Infect Dis 5: 209–215. [Google Scholar]
  19. Kublin JG, Witzig RS, Shankar AH, Zurita JQ, Gilman RH, Guarda JA, Cortese JF, Plowe CV, 1998. Molecular assays for surveillance of antifolate-resistant malaria. Lancet 351: 1629–1630. [Google Scholar]
  20. NCHS Growth Curves for Children Birth–18 Years, 1977. Hyattsville, MD: National Center for Health Statistics.
  21. Cook JD, Skikne BS, Baynes RD, 1994. Iron deficiency: the global perspective. Adv Exp Med Biol 356: 219–228. [Google Scholar]
  22. Zalewski PD, 1996. Zinc and immunity: implications for growth, survival, and function of lymphoid cells. J Nutr Immunol 4: 39–80. [Google Scholar]
  23. Walsh CT, Sandstead HH, Prasad AS, Newberne PM, Fraker PJ, 1994. Zinc: health effects and research priorities for the 1990s. Environ Health Perspect 102 (Suppl 2): 5–46. [Google Scholar]
  24. Crofton RW, Gvozdanovic D, Gvozdanovic S, Khin CC, Brunt PW, Mowat NA, Aggett PJ, 1989. Inorganic zinc and the intestinal absorption of ferrous iron. Am J Clin Nutr 50: 141–144. [Google Scholar]
  25. International Zinc Nutrition Consultative Group (IZiNCG) Technical Document No. 1, 2004. Assessment of the risk of zinc deficiency in populations and options for its control. Food Nutr Bull 25: S91–S204. [Google Scholar]
  26. Brown KH, 1998. Effect of infections on plasma zinc concentration and implications for zinc status assessment in low-income countries. Am J Clin Nutr 68: 425S–429S. [Google Scholar]
  27. WHO, 2001. Iron Deficiency Anemia Assessment, Prevention and Control: A Guide for Program Managers. Geneva: World Health Organization. WHO/NHD/01.3.
  28. Zeger SL, Liang KY, 1986. Longitudinal data analysis for discrete and continuous outcomes. Biometrics 42: 121–130. [Google Scholar]
  29. Zinc Investigators’ Collaborative Group, 1999. Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: pooled analysis of randomized controlled trials. J Pediatr 135: 689–697. [Google Scholar]
  30. Gera T, Sachdev HP, 2002. Effect of iron supplementation on incidence of infectious illness in children: systematic review. BMJ 325: 1142. [Google Scholar]
  31. Shankar AH, Genton B, Baisor M, Paino J, Tamja S, Adiguma T, Wu L, Rare L, Bannon D, Tielsch JM, 2000. The influence of zinc supplementation on morbidity due to Plasmodium falciparum: a randomized trial in preschool children in Papua New Guinea. Am J Trop Med Hyg 62: 663–669. [Google Scholar]
  32. Nacher M, McGready R, Stepniewska K, Cho T, Looareesuwan S, White NJ, Nosten F, 2003. Haematinic treatment of anaemia increases the risk of Plasmodium vivax malaria in pregnancy. Trans R Soc Trop Med Hyg 97: 273–276. [Google Scholar]
  33. Iyer JK, Shi L, Shankar AH, Sullivan DJ Jr, 2003. Zinc protoporphyrin IX binds heme crystals to inhibit the process of crystallization in Plasmodium falciparum. Mol Med 9: 175–182. [Google Scholar]
  34. Sazawal S, Black RE, Jalla S, Mazumdar S, Sinha A, Bhan MK, 1998. Zinc supplementation reduces the incidence of acute lower respiratory infections in infants and preschool children: a double-blind, controlled trial. Pediatrics 102: 1–5. [Google Scholar]
  35. Bhandari N, Bahl R, Taneja S, Strand T, Molbak K, Ulvik RJ, Sommerfelt H, Bhan MK, 2002. Effect of routine zinc supplementation on pneumonia in children aged 6 months to 3 years: randomised controlled trial in an urban slum. BMJ 324: 1358. [Google Scholar]
  36. Baqui AH, Zaman K, Persson LA, El Arifeen S, Yunus M, Begum N, Black RE, 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. [Google Scholar]

Data & Media loading...

  • Received : 04 Nov 2005
  • Accepted : 23 Feb 2006

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error