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Preventive Zinc Supplementation on Mortality and Morbidity

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Yakoob MY, Theodoratou E, Jabeen A, Imdad A, Eisele TP, Ferguson J, Jhass A, Rudan I, Campbell H, Black RE, Bhutta ZA.  Preventive zinc supplementation in developing countries: impact on mortality and morbidity due to diarrhea, pneumonia and malaria. BMC Public Health 2011; 11 (Suppl 3): S23.


  • Zinc deficiency affects 30% of the world’s population(1) and is most prevalent in children under 5 in developing countries (2).
  • Zinc deficiency is associated with impaired immune functions, resulting in an increase in morbidity due to infections, growth retardation, hypogonadism and cognitive dysfunction (3, 4)
  • Strong evidence exists for the effect of zinc in decreasing morbidity and mortality in children due to gastrointestinal and respiratory infections (5, 6) and malarial morbidity (7).
  • This review evaluates the effect of zinc in children less than 5 years of age from developing countries receiving preventive zinc supplementation for a minimum period of three months.

Intervention Effects

Preventive Zinc Supplementation on All-cause Mortality

  • Non-significant (9%) effect on all-cause mortality (RR: 0.91; 95% CI 0.82-1.01) - 7 RCTs (low quality of evidence)

Preventive Zinc Supplementation on Diarrhea-specific Morbidity and Mortality

  • Non-significant (18%) reduction in diarrhea-specific mortality (RR: 0.82; 95% CI 0.64-1.05) – 4 RCTs (low quality of evidence)
  • 13% reduction in incidence of diarrhea (RR: 0.87; 95% CI 0.81-0.94) – 14 RCTs (moderate quality of evidence)

Preventive Zinc Supplementation on Pneumonia-specific Morbidity and Mortality 

  • Non-significant (15%) reduction in pneumonia-specific mortality (RR: 0.85; 95% CI 0.65-1.11) – 4 RCTs (low quality of evidence)
  • 19% reduction in incidence of pneumonia (RR: 0.81; 95% CI 0.73-0.90) – 6 RCTs (moderate quality of evidence)

Preventive Zinc Supplementation on Malaria-specific Morbidity and Mortality 

  • No effect on malaria mortality (RR: 0.90; 95% CI 0.77-1.06) – 1 RCT (low quality evidence)
  • No effect on incidence of malaria (RR: 0.92; 95% CI 0.82-1.04) – 4 RCTs (low quality evidence)

Intervention Recommendation 

  • The most conservative estimates are recommended as a surrogate for mortality.  Therefore, zinc supplementation (for a minimum period of 3 months) in children is associated with a reduction in diarrhea mortality of 13% and pneumonia mortality of 15%.  
  • No recommendation is made for malaria due to insufficient evidence.
  • The review did not give any conclusive evidence about any possible positive or negative interaction between zinc and iron whereby iron decreases the absorption or bioavailability of zinc.

References from Yakoob Paper Cited Here

  1. Caulfield L, Black RE. Zinc Deficiency In: Comparative quantification of health risks: global and regional burden of disease attributable to selected major risk factors. Ezzati M, Lopez AD, Rodgers A, Murray CJL, editor. Geneva: World Health Organization; 2004. 
  2. Gibson RS, Ferguson EL. Assessment of dietary zinc in a population. Am J Clin Nutr. 1998;68(2 Suppl):430S–434S.
  3. Shankar AH, Prasad AS. Zinc and immune function: the biological basis of altered resistance to infection. Am J Clin Nutr. 1998;68(2 Suppl):447S–463S.
  4. Prasad AS. Discovery of human zinc deficiency and studies in an experimental human model. Am J Clin Nutr. 1991;53(2):403–412.
  5. Sazawal S, Black RE, Jalla S, Mazumdar S, Sinha A, Bhan MK. Zinc supplementation reduces the incidence of acute lower respiratory infections in infants and preschool children: a double-blind, controlled trial. Pediatrics. 1998;102(1 Pt 1):1–5. 
  6. Hambidge M, Krebs N. Zinc, diarrhea, and pneumonia. J Pediatr. 1999;135(6):661–664. 
  7. Bates CJ, Evans PH, Dardenne M, Prentice A, Lunn PG, Northrop-Clewes CA, Hoare S, Cole TJ, Horan SJ, Longman SC, et al. A trial of zinc supplementation in young rural Gambian children.  Br J Nutr 1993, 69(1): 243-255.

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