Effects of food supplementation on cognitive function, cerebral blood flow, and nutritional status in young children at risk of undernutrition: randomized controlled trial

Randomized controlled trial in 10 rural villages in the Oio and Cacheu regions of Guinea-Bissau, using village-based clusters and two enrollment cohorts about five months apart. Children aged 15 months to 7 years were enrolled, with the main analyses focused on children younger than 4 years; for the NEWSUP arm, 157 children younger than 4 and 202 children aged 4 or older were analyzed.

NEWSUP was an oral multicomponent food supplement given as a breakfast serving five mornings per week for about 23 weeks. Each serving was isocaloric at approximately 1322 kJ and was provided as a raw paste, sometimes mixed as porridge with water; the formulation contained higher protein and fat and more omega-3 fatty acids and polyphenols than the comparator foods.

NEWSUP improved working memory and cerebral blood flow in children younger than 4 years, but not in older children. In children under 4, NEWSUP versus control increased working memory in the fully adjusted model, rate ratio 1.20 (1.02 to 1.41), P=0.03, and in per-protocol analysis 1.25 (1.06 to 1.47); no significant effect was seen versus control in children aged 4 or older. Intention-to-treat analyses also showed higher cerebral blood flow and oxygen metabolism indices, including CBFi 1.14 mm2/s×10-8 (0.10 to 2.23) and CMRO2i 4.54 AU (0.64 to 8.44), with larger regional changes in the left ventrolateral prefrontal cortex versus FBF. In anemic children, NEWSUP increased hemoglobin by 0.65 g/dL (0.23 to 1.07), and compared with FBF it increased lean tissue accretion by 2.98 cm2 (0.04 to 5.92) while reducing fat accretion by -5.82 cm2 (-11.28 to -0.36). No serious adverse events occurred.

Benefits were age dependent, with no significant working memory effect in children aged 4 or older. The intervention period was only about 23 weeks, and some outcomes were analyzed in subsets such as the anemia cohort, limiting precision and generalizability. Allocation ratio was not stated, and the setting was a low-income rural population in Guinea-Bissau, so external validity may be limited.