Role of Zinc Supplementation in Children
Role of Zinc Supplementation in Children
Special Report
By Mary-Louise Scully, MD
Sansum-Santa Barbara Medical Foundation Clinic, Santa Barbara, CA
Dr. Scully reports no financial relationship relevant to this field of study.
ASTM Conference Coverage
The role of zinc supplementation in diarrheal and other infectious diseases was the focus of a Symposium at the recent Annual Meeting of the American Society of Tropical Medicine and Hygiene held in Atlanta, Georgia, November 12-16, 2006. Zinc deficiency is common in developing countries, most notably areas of Latin America, Africa, the Middle East, and South Asia. The classical syndrome of zinc deficiency secondary to a rare genetic disorder (acrodermatitis enteropathica) is characterized by dermatitis, anorexia, irritability, growth deficits, and chronic diarrhea. Numerous clinical studies (see below) have shown zinc supplementation to be effective in both the primary prevention and the treatment of diarrhea and respiratory tract infections.
Pneumonia remains a leading cause of morbidity and mortality in young children. Abdullah Brooks presented some of the studies analyzing the role of zinc in primary prevention and treatment of respiratory disease. In a randomized, controlled trial of children aged 2 to 12 months done in Bangladesh, 70 mg of zinc weekly resulted in fewer incidents of pneumonia and lower mortality.1 Another randomized study of children aged 2 to 23 months showed a reduced duration of severe pneumonia in children given 20 mg of zinc per day.2 Some possible mechanisms of zinc's positive effect in treating pneumonia might include a direct effect on decreasing lung inflammation, the promotion of cellular regeneration, and possibly enhanced bacterial clearance.
Acute diarrhea remains a leading cause of childhood deaths despite the decline in mortality since the successful promotion of oral rehydration therapy (ORT) in 1978. The World health Organization (WHO) has now recommended that in addition to ORT, zinc supplements be used in the setting of acute diarrhea. Shinjini Bhatnagar, of the All India Institute of Medical Sciences, reviewed some of the studies leading up to this recommendation beginning with a 1995 study in India.3 In this double-blind, randomized, controlled trial of 937 children ages 6 to 35 months, the children who received 20 mg of zinc daily (in addition to ORT) had a significant reduction in the severity and duration of acute diarrhea. Studies evaluating primary prevention of diarrhea, treatment of acute diarrhea, and persistent diarrhea in a variety of countries have more consistently shown zinc to be beneficial and safe. In addition, there are no studies showing an increased risk of diarrheal disease with zinc supplementation.
Henry Binder of Yale University addressed the possible mechanisms of zinc's action in diarrhea. In a rat ileum model, zinc blocks cAMP-activated potassium channels but not Ca-mediated potassium channels.4 In addition, zinc is not effective in cGMP-mediated chloride secretion. If these findings are correct, it would suggest zinc may only be effective in cAMP-mediated or heat-labile-induced toxin diarrhea and not in diarrhea secondary to rotavirus enterotoxin, Helicobacter pylori toxin, Clostridium difficile toxin, or Cryptosporidium toxin. Dr. Binder advocates further laboratory-based studies to better understand the mechanism(s) by which zinc is effective in the treatment of diarrhea.5
Despite the lack of a clear understanding of zinc's mechanism of action, the emerging clinical data prompted the WHO and UNICEF to recommend that zinc supplements at 20 mg per day for 10-14 days (10 mg per day in infants under 6 months) be given along with ORS in the routine management of acute diarrhea.6 The new recommendations alsocall for the use of low osmolarity ORS with 75 meq/l sodium and 75 meq/l of glucose with a total osmolarity of 245 mOsm/l. The previous formulation had 90 meq/l of sodium with a total osmolarity of 311 mOsm/l. The goal of the "improved" ORS was to shorten the duration of diarrhea, reduce stool volume, and reduce the need for intravenous fluids. In addition to low osmolarity ORS and zinc supplements, the new recommendations still emphasize the importance of breast feeding, continued feeding, early recognition of dehydration, and selective use of antibiotics in the management of acute diarrhea. A summary of the scientific evidence and reference material that were the basis of these recommendations can be obtained through WHO/Child and Adolescent Health and Development (CAH, email [email protected]) or the Zinc Task Force.
The next challenge will be implementing these recommendations in developing countries. Zinc supplements can be formulated as syrup or as dispersible tablets that dissolve quickly when mixed with clean water or breast milk. Ideally, the formulations of zinc supplements should mask the strong metallic aftertaste of zinc to make it more appealing to young children and reduce vomiting. The tablet formulations have the advantage of being lighter to transport, easier to store, and often have a shelf life of 2 years. Iron and zinc supplements should not be co-formulated as iron may interfere with zinc absorption. Peter Winch of the John Hopkins Bloomberg School of Public Health presented their study of a 14-day administration of zinc for childhood diarrhea in Mali.7 The levels of correct administration of zinc were good with 64 % of patients completing a 14-day course and 89% completing a 10-day course. During the study, it was noted that some children might be getting delayed malaria treatment (ie, only zinc) during episodes of fever and diarrhea secondary to malaria. Extra efforts in educating the children's caregivers about the need for both antimalarials and zinc in certain situations corrected the problem. This will be less of an issue in nonendemic malaria areas of Asia, but it may pose an added challenge to zinc implementation strategies in Africa, where a high prevalence of childhood diarrhea and malaria co-exist.
Whether infection with HIV and zinc supplementation could result in adverse effects was addressed in a recent randomized double-blind placebo-controlled trial in 96 children in South Africa.8 There were no declines in CD4 counts or increase in HIV viral load in the children treated with 10 mg of zinc daily for 6 months. Also, the children given zinc were less likely to develop watery diarrhea. In light of the small study size, the follow up being relatively short, and the fact that the children were not on any antiretroviral medications, further studies will need to confirm these findings. However, extrapolating from the data on the benefits of zinc supplements in HIV-uninfected children, it is likely that zinc, and possibly other micronutrients, will remain an important ingredient in the measures to improve the global health of children.
References:
- Brooks WA, et al. Effect of weekly zinc supplements on incidence of pneumonia and diarrhea in children younger than 2 years in an urban, low-income population in Bangladesh: randomized controlled trial. Lancet. 2005;366:999-1004.
- Brooks WA, et al. Zinc for severe pneumonia in very young children: Double-blind placebo-controlled trial. Lancet. 2004; 363:1683-1688.
- Sazawal S, et al. Zinc supplementation in young children with acute diarrhea in India. N Eng J Med. 1995;333:839-844.
- Hogue KM, et al. Zinc inhibits cAMP-stimulated Cl secretion via basolateral K-channel blockade in rat ileum. Am J Physiol. 2005;288:G956-963.
- Binder HJ, et al. Zinc in the treatment of acute diarrhea: Current status and assessment. Gastroenterology. 2006;130:2201-2205.
- Implementing the new recommendations on the clinical management of diarrhea: Guidelines for policy makers and programme directors. World Health Organization/UNICEF/USAID/Johns Hopkins Bloomberg 2006. www.who.int (accessed 2 Jan 2006).
- Winch PJ, et al. Short report: Prescription and administration of a 14 day regimen of zinc treatment for childhood diarrhea in Mali. Am Soc Trop Med Hyg. 2006;74:880-883.
- Bobat R, et al. Safety and efficacy of zinc supplementation for children with HIV-1 infection in South Africa: A randomized double-blind placebo-controlled trial. Lancet. 2005;366:1862-1867.
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