Zinc, vitamin A, and glutamine supplementation in Brazilian shantytown children at risk for diarrhea results in sex-specific improvements in verbal learning

Abstract

OBJECTIVE:To identify the impact of supplemental zinc, vitamin A, and glutamine, alone or in combination, on long-term cognitive outcomes among Brazilian shantytown children with low median height-for-age z-scores.METHODS:A randomized, double-blind, placebo-controlled trial was conducted in children aged three months to nine years old from the urban shanty compound community of Fortaleza, Brazil. Demographic and anthropometric information was assessed. The random treatment groups available for cognitive testing (total of 167 children) were: (1) placebo, n = 25; (2) glutamine, n = 23; (3) zinc, n = 18; (4) vitamin A, n = 19; (5) glutamine+zinc, n = 20; (6) glutamine+vitamin A, n = 21; (7) zinc+vitamin A, n = 23; and (8) glutamine+zinc+vitamin A, n = 18. Neuropsychological tests were administered for the cognitive domains of non-verbal intelligence and abstraction, psychomotor speed, verbal memory and recall ability, and semantic and phonetic verbal fluency. Statistical analyses were performed using SPSS, version 16.0. ClinicalTrials.gov: NCT00133406.RESULTS:Girls receiving a combination of glutamine, zinc, and vitamin A had higher mean age-adjusted verbal learning scores than girls receiving only placebo (9.5 versus 6.4, p = 0.007) and girls receiving zinc+vitamin A (9.5 versus 6.5, p = 0.006). Similar group differences were not found between male study children.CONCLUSIONS:The findings suggest that combination therapy offers a sex-specific advantage on tests of verbal learning, similar to that seen among female patients following traumatic brain injury.

Recent Advances in Understanding the Long-Term Sequelae of Childhood Infectious Diarrhea

“…The trial found that girls receiving a combination of glutamine, zinc and vitamin A had higher verbal learning scores than girls receiving placebo. 28 Other recent studies also demonstrate the continued importance of clean water, hand-washing and sanitation in ameliorating the effects of enteric disease. In a study from 2 peri-urban areas in South Africa that examined sources of drinking water, households with children under 5 years who used open-topped storage containers had the poorest water quality (taking into account heterotrophic bacteria, total coliforms, E. coli, conductivity, turbidity, pH, and total and residual chlorine).…”

Brazilian studies on zinc deficiency and supplementation: emphasis on children

“…The quality criteria in which articles presented the greatest limitation were, in particular, proof of representativeness of the sample studied in relation to the study population (in observational and experimental studies); definition of main confounding factors (in observational studies) and description of loss of participant (in observational and experimental studies). Considering that all the articles had an average or high quality and that the main risks of bias were associated with the analysis of loss of participants and confounding factors, without negative effects on the objectives of the review, we decided to systematize all the studies The analysis of sample representativeness indicates that 15 studies 16,17,19,20,29,31,34,36,[38][39][40]42,[44][45][46] used a representative sample and random selection of participants, five 15,18,21,22,37 studied a large population percentage and ten 23,24,26,27,30,32,33,35,41,43 studied populations with no characteristic of representativeness. With the exception of two studies, 25,30 representativeness was guaranteed in all others that focused on preschool children (Tables 1 and 2).…”

“…Prior knowledge suggests nutritional deficiency among children. 15,17,18,20,30 It was also observed that experimental studies [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46] have prioritized the analysis of zinc intervention effects on the nutritional status of micronutrients, 33,35,36,39,41,43,46 but present limitations in the analysis of other outcomes, such as functional parameters.…”

“…[31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46] The hypothesized effect of zinc supplementation on growth was confirmed in children living in an urban area of Fortaleza, CE, 39 and in schoolchildren of short heigth in Rio de Janeiro. 42 The three studies 31,32,44 showed a positive effect on development, according to the indicators used by the researchers. The effect of zinc supplementation on the nutritional status of micronutrients was found in six 33,35,36,41,43,46 of the studies with suchlike analyses, of which five studies 33,35,36,41,43 reported the effect on zinc nutritional status.…”

“…27 According to Table 2, the impact on growth, development and improvement of nutritional status of micronutrients was considered in five, 34,36,39,42,45 three, 31,32,44 and seven studies, 33,35,36,39,41,43,46 respectively, out of 16 experimental studies. [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46] The hypothesized effect of zinc supplementation on growth was confirmed in children living in an urban area of Fortaleza, CE, 39 and in schoolchildren of short heigth in Rio de Janeiro. 42 The three studies 31,32,44 showed a positive effect on development, according to the indicators used by the researchers.…”