Effect of zinc supplementation on mortality in children aged 1–48 months: a community-based randomised placebo-controlled trial

Sazawal, Sunil; Black, Robert E.; Ramsan, Mahdi; Chwaya, Hababu M.; Dutta, Arup; Dhingra, Usha; Stoltzfus, Rebecca J.; Othman, Mashavi K; Kabole, Fatma

doi:10.1016/s0140-6736(07)60452-8

Cited by 130 publications

(106 citation statements)

References 42 publications

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“…Zn supplementation is now recommended by the WHO alongside oral rehydration salts during treatment of acute diarrhoea in children. However, Zn does not reduce all-cause mortality (46,47) ; the effect seems to be specific to diarrhoea.…”

Section: Zincmentioning

confidence: 87%

Nutrition, intestinal defence and the microbiome

Kelly

2010

Proc. Nutr. Soc.

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The interaction between nutrition and infection was the subject of important work by several groups in the 1960s. The explosion of knowledge in immunology, including innate immunity, has led to increased understanding of the impact of nutrition on host defence, but much more work needs to be done in this area. In the last decade an increasing volume of work has opened up the previously obscure world of human endogenous flora. This work suggests that the microbiome, the total genetic pool of the microbiota, contributes to the already complex interaction between nutrition and infectious disease. The established concept that nutritional status, host defence and infection all impact on each other now has to be expanded into a multiple interaction, with the microbiota interacting with all three other elements. There is good evidence that the microbiome programmes host defence and drives a metabolome that impacts on energy balance, and indeed on some micronutrients. In turn, host defence shapes the microbiome, and nutritional status, particularly micronutrient status, helps determine several elements of host defence. While interventions in this area are in their infancy, the understanding of interactions that already have an enormous impact on global health is now at a threshold. The present review explores the evidence for these interactions with a view to putting potential interventions into the context of a conceptual framework.

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Section: Zincmentioning

confidence: 87%

Nutrition, intestinal defence and the microbiome

Kelly

2010

Proc. Nutr. Soc.

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“…However, understanding these differential effects is needed to guide public health interventions to effectively reduce infant morbidity and mortality globally. Recently, two large studies on zinc supplementation in infants and children failed to show a significant benefit of zinc supplementation in children under the age of 1 year on mortality (Sazawal et al, 2007;Tielsch et al, 2007). Perhaps, maternal zinc supplementation can be more beneficial in reducing infant mortality.…”

Section: Discussionmentioning

confidence: 99%

“…Surprisingly, two large trials of iron and zinc supplementation in children failed to find a significant beneficial effect of zinc supplementation on mortality in children under the age of 12 months (Sazawal et al, 2007;Tielsch et al, 2007). Hence, although there appears to be beneficial effects in the case of supplementation with vitamin A and zinc in children above 12 months of age, evidence is less clear for infants.…”

Section: Introductionmentioning

confidence: 99%

Maternal micronutrient supplementation with zinc and β-carotene affects morbidity and immune function of infants during the first 6 months of life

Wieringa

Dijkhuizen

Muhilal³

et al. 2010

Eur J Clin Nutr

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Background/Objectives: Micronutrient deficiencies are prevalent worldwide, and a major cause of infant death. Supplementation with multiple micronutrients during pregnancy might improve micronutrient status of the newborn, thereby reducing morbidity and death. Moreover, maternal supplementation might affect the newborn's immune development. Therefore, this study investigated the effects of maternal zinc and b-carotene supplementation on the infant's morbidity and immune function during the first 6 months of life. Subjects/Methods: Mothers were supplemented during pregnancy with b-carotene and/or zinc, in addition to iron and folic acid, in a randomized, double-blind controlled trial. Newborn infants (n ¼ 136) were followed up for 6 months. Results: Infants born from mothers receiving zinc during pregnancy had significantly fewer episodes of diarrhoea than infants born from mothers not receiving zinc (0.2 and 0.4, respectively), but more episodes of cough (1.3 and 0.9 respectively) during the first 6 months. Maternal b-carotene supplementation had no effect on infants' morbidity. Cytokine production in the newborns was affected by maternal zinc and b-carotene supplementation, with zinc supplementation giving higher interleukin-6 production (16% higher), and b-carotene supplementation leading to lower interferon-g production (36% lower). Conclusions: This study shows that maternal supplementation with zinc and b-carotene affected the newborn's immune development in specific ways, but only maternal zinc supplementation significantly affected morbidity in the infants. Addition of zinc to routine iron and folic acid supplements for pregnant women could be an effective way to reduce diarrhoeal disease during the first 6 months of life, albeit at the expense of more episodes of cough.

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“…NutriSet supplies the standard 20 mg ZnSO 4 tablets for intervention programs of the United Nations agencies as an adjuvant for routine oral rehydration. They formulated the active treatment (5 mg Zn) and placebo tablets for intervention studies in Tanzania (Sazawal et al, 2007), Nepal (Tielsch et al, 2007) and Guatemala (Mazariegos et al, 2010). Rivera (2007) commented on the first two by noting that, at the end of the intervention, the difference in average circulating Zn concentration between Zn supplement participants and controls in the subsamples with blood extraction (Sazawal et al, 2007;Tielsch et al, 2007) was only minimal (o10%).…”

Section: Discussionmentioning

confidence: 99%

“…They formulated the active treatment (5 mg Zn) and placebo tablets for intervention studies in Tanzania (Sazawal et al, 2007), Nepal (Tielsch et al, 2007) and Guatemala (Mazariegos et al, 2010). Rivera (2007) commented on the first two by noting that, at the end of the intervention, the difference in average circulating Zn concentration between Zn supplement participants and controls in the subsamples with blood extraction (Sazawal et al, 2007;Tielsch et al, 2007) was only minimal (o10%). Such small increments were below the range of effect sizes generally seen in similar age groups receiving daily Zn doses of 5-10 mg/day for comparable durations.…”

Section: Discussionmentioning

confidence: 99%

Bioavailability of zinc from NutriSet zinc tablets compared with aqueous zinc sulfate

Nw¹,

Me²,

Weiss

et al. 2010

Eur J Clin Nutr

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Background/Objectives: The apparent widespread extent of zinc (Zn) deficiency in developing countries and the efficacy of oral Zn supplements as an adjunct to oral rehydration therapy make oral Zn supplementation an increasingly important modality in clinical medicine and public health. In this study we aimed to compare the relative bioavailability of oral doses of 30 mg of Zn in two dosing forms Subjects/Methods: In total, 10 healthy male volunteers ingested oral Zn doses with 200 ml plain water at about 0830 hours in the fasting state on two occasions, once as 30 mg of Zn in an aqueous solution of reagent grade zinc sulfate (ZnSO 4 ) and another time as 1.5 NutriSet Zn tablets (Nutriset, Malaunay, France); on a third occasion, only plain water was consumed. Venous blood specimens were collected at baseline, 60, 120, 180 and 240 min after ingestion and the plasma Zn was measured for each sample. Results: The relative bioavailability of oral Zn from a commonly used, tableted (NutriSet) form is only about half of that of a reference dose of aqueous ZnSO 4 as indicated by the area under the curve of serial plasma Zn excursion and maximal change in circulating Zn. Conclusions: Reduced or absent functional outcomes in Zn intervention trials may derive, in part, from a lower than anticipated intestinal uptake of the Zn in the tableted form.

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Effect of zinc supplementation on mortality in children aged 1–48 months: a community-based randomised placebo-controlled trial

Cited by 130 publications

References 42 publications

Nutrition, intestinal defence and the microbiome

Nutrition, intestinal defence and the microbiome

Maternal micronutrient supplementation with zinc and β-carotene affects morbidity and immune function of infants during the first 6 months of life

Bioavailability of zinc from NutriSet zinc tablets compared with aqueous zinc sulfate

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