Zinc supplementation in malnourished children with persistent diarrhea in Pakistan

Objective. To evaluate the potential benefit of dietary supplementation of a rice-lentil (Khitchri) and yogurt diet with 3 mg/kg/d of elemental zinc (as zinc sulfate) in hospitalized malnourished children (age 6-36 months) with persistent diarrhea for 14 days. Methodology. Randomized, double-blind placebo-controlled trial. Setting. Nutrition Research Ward at the National Institute of Child Health, Karachi, Pakistan, where children were admitted for 14 days of inpatient supervised rehabilitation. Main Outcome Measures. Primary outcome: overall weight gain by day 14. Secondary outcomes: overall energy intake, stool output, time to diarrheal recovery and weight gain (greater than or equal to 3 days), plasma zinc, copper, prealbumin, and insulin-like growth factor-1. Results. Of 87 children randomized for supplementation with either zinc or placebo, the two groups were comparable at admission in terms of severity and duration of diarrhea, as well as nutritional and anthropometric parameters. The overall weight gain, stool volume, stool frequency, as well as the time taken for diarrheal recovery or steady weight gain, were comparable for both supplemented children and controls. Supplemented children had a significant improvement in plasma zinc levels and serum alkaline phosphatase by day 14 of therapy in comparison with controls. Plasma copper levels were low in both groups at admission and although an increase was seen in control children, levels decreased further after zinc supplementation. There was no significant difference between the two groups for hemoglobin, serum albumin, prealbumin, and plasma insulin-like growth factor-1 increments during the course of therapy. Evaluation of primary and secondary outcome criteria among the subset of children with plasma zinc levels <60 mu g/d at admission did not reveal any significant differences. Conclusions. Although there was satisfactory recovery in malnourished children with persistent diarrhea receiving the Khitchri-yogurt diet, there was no evidence of improved weight gain or acceleration of recovery from diarrhea with zinc supplementation. In contrast the reduction in plasma copper levels in zinc-supplemented malnourished children suggests that caution should be exercised in supplementing severely malnourished children with zinc alone.