Zinc deficiency is one of the ten biggest factors contributingto burden of disease in developing countries with high mortality.1Since the problem was highlighted in the World Health Report2002, calls have increased for supplementation and food fortificationprogrammes.23 Zinc interventions are among those proposed tohelp reduce child deaths globally by 63%.4 Populations in SouthEast Asia and sub-Saharan Africa are at greatest risk of zincdeficiency; zinc intakes are inadequate for about a third ofthe population and stunting affects 40% of preschool children.5Zinc is commonly the most deficient nutrient in complementaryfood mixtures fed to infants during weaning.6
Improving zinc intakes through dietary improvements is a complextask that requires considerable time and effort.7 The case forpromoting the use of zinc supplements and for fortifying foodswith zinc, especially those foods commonly eaten by young children,therefore seems strong. However, global policies or recommendationsfor zinc interventions are few. The World Health Organizationrecommends zinc only as a curative intervention, either as partof the mineral mix used in the preparation of foods for thetreatment of severe malnutrition, or more recently in the treatmentof diarrhoea.8 We review current evidence that improving zincintake has important preventive or curative benefits for mothersand young children and examine the programme implications forachieving this in developing countries.
Sources and selection criteria
We searched PubMed and the databases of WHO and Unicef for informationon zinc supplementation and zinc fortification. We examinedexisting reviews of the evidence for benefits of zinc supplementationand zinc fortification and recent papers reporting the resultsof randomised controlled trials. These findings were furtherconsidered in the light of international policy recommendationsfor supplementation and fortification of other micronutrientssuch as iodine, iron, and vitamin A and reviews of experiencein the implementation of these programmes.
Strong evidence exists that zinc supplements improve the prognosisof children being treated for diarrhoeal disease. A pooled analysisof randomised controlled trials of therapeutic zinc in childrenwith diarrhoea showed that children with acute diarrhoea givenzinc supplements had a 15% lower probability of continuing diarrhoeaon a given day compared with those in the control group; childrenwith persistent diarrhoea had a 24% lower probability of continuingdiarrhoea. In addition, children with persistent diarrhoea hada 42% lower rate of treatment failure or death if given zincsupplements.9
Zinc deficiency is common in developing countrieswith high mortality
Regular zinc supplements can greatly reducecommon infant morbidities in developing countries
Zinc is alsoan effective adjunct treatment for diarrhoeal disease
Zincdeficiency commonly coexists with other micronutrient deficienciesincluding iron, making single supplements inappropriate
Untilthe results of trials of multiple micronutrient interventionsare available, zinc supplements should be given to childrenwith infections
The most effective way to deliver zinc supplements in diarrhoealdisease control programmes is not yet clear. Since zinc supplementationreduces the duration and severity of diarrhoeal episodes itmight be beneficial to add zinc to oral rehydration solution;one of the shortcomings of oral rehydration therapy is thatthe frequency and volume of stools is not reduced. However,studies of the efficacy of including zinc in oral rehydrationsolutions are not conclusive.10 In addition, many countriespromote the use of home made fluids.
WHO and Unicef propose to distribute blister packs of 10 dispersibletablets of 20 mg zinc for daily consumption as the part of thetreatment of diarrhoea. The use of zinc as an adjunct therapysignificantly improves the cost effectiveness of standard managementof diarrhoea.11 Achieving and maintaining high levels of coverageof current interventions for diarrhoeal disease, such as oralrehydration therapy, are already proving difficult.12 The challengeof promoting zinc supplements to treat diarrhoea is thereforeconsiderable.
Preventive action Regular zinc supplements have been shown to prevent disease.Supplementation seems to be most beneficial in children withlower birth weights and those with stunted growth or zinc deficiency.The supplementation of low birthweight infants in Brazil frombirth for 8 weeks reduced both diarrhoea and coughs by a thirdin the first six months of life.w2 Pooled analysis of randomisedcontrol trials found that zinc supplements reduced diarrhoealdiseases by 18% and pneumonia by 41% in preschool children.13The results for pneumonia are remarkable considering the challengethat pneumonia presents from a child health perspective.14 Zincsupplementation has also been shown to reduce cases of falciparummalaria presenting at health centres in Africa and Papua NewGuinea.w3 w4 Zinc supplementation of babies with low birth weightin India reduced mortality during infancy by a third.15 Maternalzinc supplementation during pregnancy improves neonatal immunestatus, early neonatal morbidity, and infant infections butnot birth weight.w1
Zinc supplementation may also prevent failure of child growth,although the evidence is weaker than for prevention of disease.A meta-analysis of randomised controlled trials of the effectsof supplemental zinc on growth of prepubertal children foundthat height and weight growth were only moderately improved,and the greatest responses were shown by children who were initiallyunderweight or stunted.16 Zinc supplementation trials in infantswith birth weights > 2.5 kg have shown little effect on preventinggrowth faltering in the second half of infancy in Indonesia.w5 w6 In Ethiopia, zinc supplements increased length growth ofstunted infants, but these infants were not selected on birthweightcriteria.w7 Trials in infants from birth to 6 months in Bangladeshshowed growth effects only in those with initial low zinc status.w8
Adding zinc to treatment for diarrhoeal disease is the first step to tackle deficiency
Credit: CAROLINE PENN/PANOS
Administering supplements Consensus is growing that zinc should not be promoted as a singlenutrient supplement for preventing zinc deficiency in youngchildren and their mothers. This is because many people havemultiple micronutrient deficiencies. Anaemia is a marker forboth iron and zinc deficiency. The use of iron and folate supplementsto treat and prevent anaemia during pregnancy and lactationhas been recommended for three decades,w9 and iron for the treatmentof anaemia in young children for almost a decade.w10 Progressin reducing anaemia in developing countries has, however, beendisappointing,w11 largely because of poor execution of programmes,especially the inadequate preparation of health staff and systemsto deliver the supplements.17w12 In addition, only a half ofanaemia is thought to be solely due to iron deficiency; othermicronutrients, such as vitamin A and vitamin C, are implicatedas well as infection and blood loss.w13 The diets of anaemicwomen in developing countries are more often deficient in micronutrientsthan they are deficient in energy.18w14 w15 Infant diets alsocommonly have inadequacies in zinc and iron as well as B vitamins.19
Zinc, iron, vitamin A, and copper all potentially interact andinterfere with each other's absorption and metabolism when usedas single nutrient supplements.2021w16 Trials are ongoingof a multiple micronutrient supplement formulated by WHO, Unicef,and United Nations University for mothers during pregnancy andlactationw17 w18; this supplement could eventually replace ironand folate if proved effective. Various trials of multiple micronutrientsas preventive supplements during infancy and childhood havebeen carried out or are under way.w19 w20 w21 w22 The resultsof this research need to be brought together to determine whetherto promote multiple micronutrient supplementation programmesduring pregnancy, lactation, and infancy.
The case for promoting fortification of foods with zinc in developingcountries may seem strong, but experience of how best to doit is limited and it may not be a suitable approach in manycountries. Most experience in food fortification comes fromindustrialised countries, where few governments mandate zincfortification. Food fortification with micronutrients in developingcountries is largely limited to iodine, with over 70% of householdsconsuming adequately iodised salt in 2000 compared with lessthan 20% in 1990.w23 Developing countries in the Latin Americanregion have the greatest experience of iron fortification, whichis mandated for wheat flour in most of the region, althoughthe effectiveness of these interventions has not been verified.w24 w25 Research into zinc fortification either as a single nutrientor as part of a multimicronutrient approach is incipient.22Innovative approaches will be needed to achieve fortificationof foods with zinc in developing countries with the highestmortalities. These include the development of small scale communityapproaches for multiple micronutrient fortification, using hammermills, and the use of condiments, fish paste, and bouillon cubes.w26 w27
International Zinc NutritionConsultative Group (www.izincg.ucdavis.edu/publications/default.html)—Thewebsite contains information on the public health importanceof zinc and many of the references used in this article areavailable there as pdf files
Independent of the food vehicle, the risks of interactions infood fortificants are still unknown. For example, zinc and ironare known to have interactionsw2823 that are likely to be compoundedby variations in the adequacy of nutritional status for othernutrients such as vitamin B6.w29 Research is ongoing into theappropriate dose and form of zinc to fortify foods.
Increased consumption of foods with a high content of absorbablezinc is the long term sustainable solution to problems of zincdeficiency. Strategies are being developed that target agriculturaland food production, household food processing, and dietarymodification.5 Zinc is highly correlated with the protein contentof foods, but the availability of zinc in protein rich plantfoods is much less than that in animal protein foods. Plantbreeding efforts aim to produce new cereal varieties with higherzinc concentrations that are more available by reducing concentrationsof inhibitors such a phytate and increasing enhancers of absorptionsuch as the sulphurous amino acids. At the household level,food processing methods for increasing the availability of zincin cereal grains and legumes include sprouting, fermenting,and soaking. These programme interventions are complex and requireconsiderable investment in behaviour change, which takes time.As yet no evidence exists of their effectiveness for preventingzinc deficiency, especially in mothers and young children.
Zinc intakes are commonly inadequate, especially in the populationsof developing countries with the highest mortality. Correctingthis situation will have dramatic impact on the morbidity andmortality of young children and modest effects on their growth.Tackling zinc deficiency in isolation, however, is inappropriate.In particular, it is important to avoid any further fragmentationof health interventions by creating an additional zinc programme.Including zinc in multiple micronutrient supplementation andfortification interventions and promoting their use throughexisting programmes aimed at tackling anaemia will be less disruptive.But these approaches are still being researched. In the meantime, the use of zinc to treat diarrhoeal disease is the mostappropriate entry point for zinc supplementation efforts. Thecost of the micronutrient supplements is miniscule comparedwith the cost of the delivery system, and the greatest challengefor programmes will continue to be achieving high levels ofcoverage. If these challenges can be met, the chances of achievingthe millennium development goals for child survival will beconsiderably enhanced.
Contributors: RS is the main author and guarantor. He developedthe first draft and made revisions based on the comments ofthe other authors. The final version was approved by all authors.
Competing interests: RS was funded by Unicef to write the paper,which was written at their request.
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