Apolipoprotein E4 influences growth and cognitive responses to micronutrient supplementation in shantytown children from northeast Brazil

Abstract

OBJECTIVE:Apolipoprotein E4 may benefit children during early periods of life when the body is challenged by infection and nutritional decline. We examined whether apolipoprotein E4 affects intestinal barrier function, thereby improving short-term growth and long-term cognitive outcomes in Brazilian shantytown children.METHODS:A total of 213 Brazilian shantytown children with below-median height-for-age z-scores (HAZ) received 200,000 IU of retinol (every four months), zinc (40 mg twice weekly), or both for one year, with half of each group receiving glutamine supplementation for 10 days. Height-for-age z-scores, weight-for-age z-scores, weight-for-height z-scores, and lactulose:mannitol ratios were assessed during the initial four months of treatment. An average of four years (range 1.4-6.6) later, the children underwent cognitive testing to evaluate non-verbal intelligence, coding, verbal fluency, verbal learning, and delayed verbal learning. Apolipoprotein E4 carriage was determined by PCR analysis for 144 children.RESULTS:Thirty-seven children were apolipoprotein E4(+), with an allele frequency of 13.9%. Significant associations were found for vitamin A and glutamine with intestinal barrier function. Apolipoprotein E4(+) children receiving glutamine presented significant positive Pearson correlations between the change in height-for-age z-scores over four months and delayed verbal learning, along with correlated changes over the same period in weight-for-age z-scores and weight-for-height z-scores associated with non-verbal intelligence quotients. There was a significant correlation between vitamin A supplementation of apolipoprotein E4(+) children and improved delta lactulose/mannitol. Apolipoprotein E4(-) children, regardless of intervention, exhibited negative Pearson correlations between the change in lactulose-to-mannitol ratio over four months and verbal learning and non-verbal intelligence.CONCLUSIONS:During development, apolipoprotein E4 may function concomitantly with gut-tropic nutrients to benefit immediate nutritional status, which can translate into better long-term cognitive outcomes.

Zinc treatment ameliorates diarrhea and intestinal inflammation in undernourished rats

“…Recent data from studies in developing countries, including Brazil and Peru, have documented a lasting impact of diarrhea (as with malnutrition and intestinal helminthic infections) on child development with ill effects on cognition, growth, and educational performance [3-5]. …”

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).…”

Reducing neurodevelopmental disorders and disability through research and interventions

“…This field of research has also significantly advanced our understanding of the inter-relationships between genetics (for example, neuroprotective APOE polymorphisms), enteric diseases, nutritional malabsorption and neurodevelopment in young children 48,49 . An important research opportunity provided by this work involves the clinical evaluation of the neurodevelopmental benefits of micronutrient interventions to enteric disease, including whether glutamine works better than glucose as a key ingredient of oral rehydration and repair therapy (ORRT) 50 . Glutamate intervention may be more effective in the repair of intestinal barrier functions and hence improve child development as well as the absorption of ARV drugs in children with HIV.…”