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Am J Clin Nutr. 2008 Mar;87(3):723-33.

Dose-response trial of prophylactic zinc supplements, with or without copper, in young Ecuadorian children at risk of zinc deficiency.

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Department of Nutrition, Program in International and Community Nutrition, University of California, Davis, Davis, CA 95616, USA.



Multiple studies have shown the benefits of zinc supplementation among young children in high-risk populations. However, the optimal dose and safe upper level of zinc have not been determined.


The objectives of this study were to measure the effects of different doses of supplemental zinc on the plasma zinc concentration, morbidity, and growth of young children; to detect any adverse effects of 10 mg supplemental Zn on markers of copper or iron status; and to determine whether any adverse effects are alleviated by providing copper with zinc.


This randomized, double-masked, community-based intervention trial was conducted in 631 Ecuadorian children who were 12-30 mo old at baseline and who had initial length-for-age z scores <-1.3. Children received 1 of 5 daily supplements for 6 mo: 3, 7, or 10 mg Zn as zinc sulfate, 10 mg Zn + 0.5 mg Cu as copper sulfate, or placebo.


The change in plasma zinc concentration from baseline was positively related to the zinc dose (P < 0.001). Zinc supplementation, including doses as low as 3 mg/d, reduced the incidence of diarrhea by 21-42% (P < 0.01). There were no other significant group-wise differences.


Zinc supplementation with a dose as low as 3 mg/d increased plasma zinc concentrations and reduced diarrhea incidence in the study population. There were no observed adverse effects of 10 mg Zn/d on indicators of copper or iron status. The current tolerable upper level of zinc recommended by the Institute of Medicine should be reassessed for young children.

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