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Multi-nutrient fortified formula improved processing speed in healthy children aged 3-6 years compared to control milkDid a fortified milk drink boost processing speed in healthy preschoolers?

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Key Takeaway
Consider that multi-nutrient fortified formula improved processing speed but not full-scale intelligence in healthy children aged 3-6 years.

This cluster-randomized, double-blind, controlled trial evaluated the effects of a multi-nutrient fortified formula versus standard control milk in 120 healthy children aged 3 to 6 years. The study was conducted across four kindergarten classes with a follow-up period of 9.0 months. Safety parameters and growth were monitored throughout the intervention period.

The primary outcome, Full Scale Intelligence Quotient (WPPSI-IV), showed no significant difference between groups, with an adjusted mean difference of 1.05 points (95% CI: -1.42, 3.52; p = 0.400). However, the Processing Speed Index demonstrated a significant improvement in the intervention group, with an adjusted mean difference of 5.91 points (95% CI: 1.88, 9.93; p = 0.004).

Secondary outcomes indicated increased gut microbial alpha diversity (Shannon index) and gut microbial abundance, alongside elevated fecal 2-hydroxybutyric acid (2-HB). A positive association was observed between increases in alpha diversity and 2-HB with improvements in the Processing Speed Index (both p < 0.05). Specific effect sizes for these secondary outcomes were not reported.

Tolerability was excellent, as all children maintained normal growth and safety parameters, with no reported adverse events, serious adverse events, or discontinuations. Limitations regarding causality and funding were not reported in the provided data. The clinical relevance of these specific gut microbial changes on cognitive processing in this age group requires further investigation.

Imagine a classroom where every child is learning to read and solve puzzles. Now imagine giving half of them a special milk drink while the other half drinks regular milk. This study did exactly that with 120 healthy children aged three to six years across four kindergarten classes. They wanted to know if adding extra nutrients to the milk would make young minds sharper.

After nine months, the results showed a clear winner in one area. Children drinking the fortified formula processed information significantly faster than those on the standard milk. Their scores on this specific task improved by an average of nearly six points. However, the overall measure of general intelligence did not change between the two groups.

The study also found that the special drink changed the gut bacteria in a good way. It increased the variety of microbes and raised levels of a specific acid linked to brain health. Researchers noted that these positive gut changes seemed to go hand-in-hand with the faster thinking speed. No safety issues or side effects were reported, and all children grew normally.

It is important to remember that this was a small study involving only 120 children. While the results are promising for processing speed, they do not prove that this drink will make every child smarter overall. More research is needed to confirm if these benefits hold true for larger groups of kids.

What this means for you:
Fortified milk improved processing speed in preschoolers without changing overall intelligence scores.

Study Details

Study typeRct
EvidenceLevel 2
Follow-up9.0 mo
PublishedApr 2026
View Original Abstract ↓
BACKGROUND/OBJECTIVES: The preschool period is critical for neurodevelopment, yet evidence investigating fortified formula's effect and potential microbiota-gut-brain axis mechanisms in this age group is limited. To evaluate fortified formula milk's effect on neurodevelopment and explore potential microbiota-gut-brain axis mechanisms in preschool children. METHODS: In this 9-month cluster-randomized, double-blind, controlled trial, 120 healthy children aged 3-6 years from four kindergarten classes were stratified by grade and randomly allocated (1:1) to receive either multi-nutrient fortified formula (intervention, = 60) or standard control milk ( = 60). Neurocognitive function was assessed using the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV). Safety was evaluated through anthropometry and blood biochemistry. Gut microbiota (16S rRNA sequencing) and fecal metabolomes (untargeted LC-MS) were analyzed at baseline and 9 months. RESULTS: The intention-to-treat (ITT) analysis showed no significant difference in Full Scale Intelligence Quotient (adjusted mean difference: 1.05 points; 95% CI: -1.42, 3.52; = 0.400). However, the intervention group significantly improved the Processing Speed Index (adjusted mean difference: 5.91 points; 95% CI: 1.88, 9.93; = 0.004), increased gut microbial alpha diversity (Shannon index) and abundance. Metabolomic analysis revealed elevated fecal 2-hydroxybutyric acid (2-HB), a marker of propanoate metabolism. Increases in both and 2-HB levels showed a positive association with PSI improvement (both < 0.05). All children maintained normal growth and safety parameters. CONCLUSIONS: Fortified formula milk improved processing speed in preschoolers, a benefit associated with gut ecosystem modulation characterized by enrichment and upregulated microbial propanoate metabolism. These results offer preliminary evidence for the role of the microbiota-gut-brain axis in nutritional cognitive programming during early childhood. (Clinical Trial Registry: ChiCTR2400084211).
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