Zinc and rehabilitation from severe protein-energy malnutrition: higher-dose regimens are associated with increased mortality

A randomized, double-blind trial was undertaken to measure the effects of zinc supplementation on catch-up growth in severe protein-energy malnutrition, with particular reference to linear growth. One hundred forty-one children between the ages of 6 mo and 3 y were enrolled after admission to a nutritional rehabilitation unit in Dhaka, Bangladesh, and randomly assigned to receive elemental zinc by mouth, 1.5 mg/kg for 15 d, 6.0 mg/kg for 15 d, or 6.0 mg/kg for 30 d, and thereafter they were followed for a total of 90 d. Anthropometric outcome measures included change in knee-heel length, midupper arm circumference, subscapular and triceps skinfold thicknesses, and change in height-for-age, weight-for-age, and weight-for-height z scores. Higher zinc doses were not associated with significant change in any anthropometric measurement, but mortality was significantly greater in children who received high-dose zinc (6.0 mg/kg) initially as opposed to those who received low-dose zinc supplementation (1.5 mg/kg) (Yates-corrected chi-square P value of 0.033 and a risk ratio of 4.53: 95% CI: 1.09 < risk ratio < 18.8). We conclude that there is no benefit to using high-dose zinc supplementation regimens and that they could contribute to increased mortality in severely malnourished children.