ZINC FOR THE PREVENTION OF DIARRHEA
Santosh SinghMedical Sciences Department,Pediatric Oncall
Address for Correpondence: Dr Santosh Singh,Medical Sciences Department, Pediatric Oncall, 1/B Saguna, 271/B St. Francis Road, Vile Parle (W), Mumbai 400056.
Diarrhoea is a common and worldwide problem. Despite much progress in the understanding of pathogenesis and of management, diarrhoeal illnesses remains one of the most important causes of global childhood mortality and morbidity. Treatment & prevention of dehydration by oral rehydration salts (ORS) is the mainstay of treatment. Oral rehydration therapy is however not the solution for prevention of diarrhoea .ORS does not reduce the duration nor the risk of persistent diarrhea. Additional therapy is required. Zinc in child health The importance of the role of zinc in human health has been known since long. Zinc is essential for more than 300 enzymes, structural proteins and hormones. It is needed for diverse physiological processes and metabolic functions including many aspects of the immune system. (1)Lack of zinc is associated with atrophy of the thymus, a gland which has a role in the maturation of lymphocytes, and the function of "T" lymphocytes is especially vulnerable to deficiency of this mineral. Zinc deficiency is associated with a reduction in delayed type hypersensitivity, and other immune responses mediated by T cells. In zinc deficiency there is an imbalance in the production of T helper cells with different functions; there is a shift from T cells (Th1) which have a predominately cellular function and are important in the defense against viral and intracellular pathogens in favour of T cells (Th2) which are involved in the production of antibodies. (2) On the other hand in experimentally induced zinc deficiency in animals there is also a reduction in the production of antibodies and in the function of the natural killer cells. Further studies will elucidate the role of zinc in the immune system and increase our understanding of how and when this mineral can be best used to prevent and treat infection. Zinc is also needed for cell replication and is thus essential for the regeneration of the intestinal mucosa, the healing of wounds and the turnover of epithelial cells necessary to maintain healthy skin. The combination of these essential functions explains why zinc plays such an important part in the protection against infections.
Diet and zinc
Despite the widespread presence of zinc in common foods, dietary deficiency is common because biovailability of zinc is reduced by the coexistence of inhibitory substances such as fiber and phytates in food of vegetable origin. These substances inhibit the absorption of zinc. The diets of the poorest populations are a poor source of zinc being largely made up of vegetable staples with little content of animal products, especially flesh foods such as meat, fish which are rich sources of easily assimilated zinc. Children in these communities do not manifest obvious signs of zinc deficiency but have often been found to have low plasma zinc levels compatible with subclinical zinc deficiency. Unlike other essential micronutrients like iron and vitamin A, there are no conventional tissue reserves of zinc that can be released or sequestered quickly in response to variations in dietary supply.(3)Given the diverse array of biological functions of zinc, it is not surprising that multiple physiological and metabolic functions, such as physical growth, immunocompetence, reproductive function, and neurobehavioral development are all affected by zinc status. When the supply of dietary zinc is insufficient to support these functions, biochemical abnormalities and clinical signs may develop. Recent investigations suggest that Zinc deficiency may be contributing to the high illness rates in these populations.(3)Thus, zinc supplementation of high risk populations has considerable potential and the search for simple economic options to counteract zinc deficiency should be given priority.
Prevention of diarrhoea
With respect to morbidity and mortality from diarrhoea, the developed world has benefited enormously from substantial improvements in hygiene, sanitation, health, and nutrition with severe disease mostly confined to agents capable of adapting to or resisting these changes. In developing countries, such prevention measures are largely hindered by climatic, social, and economic factors and resultant morbidity remains high. Globally, little is being done to improve the situation, despite evidence that appropriate water, hygiene, and sanitation interventions can reduce diarrhoea incidence by 26% and mortality by 65%. The situation is much the same for malnutrition, which requires an urgent and concerted action.(4)Persistent diarrhoea is closely linked to nutritional status. It often occurs in children who are undernourished and has significant nutritional consequences. Therefore, addressing nutritional issues is an important part of case management of children with persistent diarrhoea.(5,6) Diarrhea is associated with an increased loss of zinc in faeces so that one would expect that children with diarrhea would be at an increased risk of zinc deficiency.(7) These findings suggest that zinc supplements may represent an important therapeutic advance complementing the oral rehydration therapy which is currently recommended to prevent dehydration but which does not reduce the duration of the diarrhea.If zinc supplements are of benefit in treating diarrhea especially in children with low blood zinc levels it is logical to think that prevention of deficiency by regular suplementation might reduce the burden of illness in populations subject to zinc deficiency.
Evidence for Zinc in the prevention of Diarrhea
Zinc plays a part in the maintenance of epithelial and tissue integrity through promoting cell growth and suppressing apoptosis and through its underappreciated role as an antioxidant, protecting against free radical damage during inflammatory responses. Thus, in the case of diarrhoea, multiple functions of zinc may help to maintain the integrity of the gut mucosa to reduce or prevent fluid loss. Notably, these responses can occur within 48 hours, much more rapidly than the direct effects of zinc on cellular development. (8)A number of randomized controlled trials have demonstrated significant reduction in the incidence and duration of acute and persistent diarrhea in zinc-supplemented children compared to their placebo-treated counterparts.(9, 10)A pooled analysis of randomized, controlled trials of zinc supplementation performed in nine low-income countries in Latin America and the Caribbean, South and Southeast Asia, and the Western Pacific, demonstrated that supplemental zinc led to an 18% reduction in the incidence of diarrhea and a 25% reduction in the prevalence of diarrhea (11). While the pooled analysis did not find differences in the effect of zinc by age, baseline serum zinc status, presence of wasting, or sex, the relevance of zinc supplementation to various geographic regions of the world remained unclear. Recent studies from Africa using zinc supplementation in young children indicate significant benefit on diarrhea burden indicating that the effect may be consistent across various geographical regions (12,13) and even if zinc is administered with oral rehydration solution.(14) Recent studies in Bangladesh of using zinc in the treatment of diarrhea in a community setting have also demonstrated substantial reduction in concomitant use of antibiotics by health-care providers (15), thus suggesting that there may be additional benefits to the use of zinc in the treatment of diarrhea.Zinc decreases the length and severity of the diarrhoea. Zinc being important for the child's immune system will help the child fight off new episodes of diarrhoea in the 2-3 months following treatment. Zinc also improves appetite and growth. Findings suggest that zinc supplementation given for 10-14 days lowers the incidence of diarrhoea in the following 2-3 months.(16) New recommendations, formulated by UNICEF and WHO in collaboration with the United States Agency for International Development (USAID) and experts worldwide, take into account new research findings while building on past recommendations. Success in reducing death and illness due to diarrhoea depends on acceptance of the scientific basis and benefits of these therapies by governments and the medical community. It also depends on reinforcing family knowledge of prevention and treatment of diarrhoea, and providing information and support to families. WHO and UNICEF therefore have recommend daily 20 mg zinc supplements for 10-14 days for children with acute diarrhoea, and 10 mg per day for infants under six months old, to curtail the severity of the diarrhoeal episode and prevent further occurrences in the ensuing 2-3 months.
Zinc is an essential trace element important for almost all biological systems.
Inadequate zinc intake has profound effects on almost all facets of the immune system, on the mucosal integrity, and on epithelial function.
Years of zinc research have resulted in new treatment recommendations for diarrhea.
Children that are given zinc regularly have a reduced burden of diarrhea an important cause of childhood mortality.
Thus , Zinc is useful in prevention of diarrhoea .
Shankar AH, Prasad AS. Zinc and immune function: the biological basis of altered resistance to infection.Am J Clin Nutr 1998;68(suppl):447S-63S
Sprietsma JE. Zinc controlled Th1/Th2 switch significantly determines the development of diseases.Medical Hypotheses 1997;49:1-14
The Role of Zinc in Child Health in Developing Countries: Taking the Science where it Matters. Editorial. Indian Pediatrics. May 2004; 41:429-433
Nikhil Thapar, Ian R Sanderson. Diarrhoea in children: an interface between developing and developed countries. Lancet. February 2004; 363:641-653
Bhutta ZA, Bird SM et al. Therapeutic affects of oral zinc in acute and persistent diarrhoea in children in developing countries: pooled analysis of randomized controlled trials. Am J Clin Nutr. 2000 Dec; 72(6):1516-22
Bhutta ZA, Gishan F et al. Persistent and chronic diarrhoea and malabsorption: Working Group report of the second World Congress of Pediatric Gastroenterology,Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr. 2004 Jun; 39 Suppl 2:S711-6
Castillo-Duran C, Vial P, Uauy R. Trace mineral balance during acute diarrhea in infants. J Pediatr 1988;113:452-7
Science commentary.What does zinc do? BMJ 2002;325:1062
Ruel MT, Rivera JA, Santizo MC, Lonnerdal B,Brown K H. Impact of Zinc supplementation on morbidity from diarrhea and respiratory infections among rural Guatemalan Children.Pediatrics 1997; 99: 808-813.
Sazawal S, Black R, Bhan M, Bhandari N, Sinha A, Jalla S. Zinc supplementation in young children with acute diarrhea in India. New Engl J Med 1995; 333: 839-844.
Bhutta ZA, Black RE, Brown KH, Gardner JM, Gore S, Hidayat A, et al. Therapeutic effect of oral zinc in acute and persistent diarrhea in children in developing countries: pooled analysis of randomized controlled trials.Am J Clin Nutr 2000; 72: 1516-1522
Muller O, Becher H, Baltussen van Zweeden A, Ye Y, Diallo DA, Konate AT, et al. Effect of zinc supplementation on malaria and other causes of morbidity in west African children: randomised double blind placebo controlled trial. BMJ 2001; 322: 1-6.
Umeta M, West CE, Haidar J, Deurenberg P, Hautvast JG..Zinc supplementation and stunted infants in Ethiopia: a randomised controlled trial. Lancet 2000; 355: 2021-2026.
Bhatnagar S, Bahl R, Sharma PK, Kumar GT, Saxena SK, Bhan MK. Zinc with oral rehydration therapy reduces stool output and duration of diarrhea in hospitalized children: a randomized controlled trial. J Pediatr Gastroenterol Nutr 2004; 38: 34-40.
Baqui AH, Black RE, El Arifeen S, Yunus M, Chakraborty J, Ahmed S, et al. Effect of zinc supplementation started during diarrhoea on morbidity and mortality in Bangladeshi children: community randomised trial. BMJ.2002; 325: 1059.
Bhutta Z.A., Black, R.E., Brown K. H., et al., 'Prevention of diarrhoea and pneumonia by zinc supplementation in children in developing countries:Pooled analysis of randomized controlled trials', 'Zinc Investigators' Collaborative Group, Journal of Paediatrics,vol. 135, no. 6, December 1999,pp. 689-697.
Last updated on 15-03-2007 Vol 4 Issue 3 (SUppl) Art # S2
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Singh S. Zinc For The Prevention Of Diarrhoea .Pediatric Oncall [serial online] 2007 [cited 15 March 2007(Supplement 12)];4. Art # S2. Available from: