Nutrition Metabolomics and Cognitive Health: A Systematic and Integrative Review

Introduction: Cognitive decline and neurodegenerative disorders represent major global health challenges, with nutrition recognized as a potentially modifiable factor influencing brain health across the lifespan. Nutrition metabolomics enables the identification of diet-derived and endogenous metabolites associated with cognitive function. However, evidence remains heterogeneous across populations, dietary exposures, analytical platforms, and cognitive assessments. This systematic and integrative review aimed to synthesize evidence on metabolomics-based biomarkers linking nutrition to cognitive health.

Methods: PubMed, Scopus, and Web of Science were systematically searched for studies published between January 2010 and December 2025, following PRISMA guidelines. Eligible studies included human observational or intervention research applying metabolomics or lipidomics to examine associations between dietary exposures, biological metabolites, and cognitive outcomes. Animal studies, reviews, conference abstracts, studies without cognitive assessment, and investigations not using metabolomic or lipidomic approaches were excluded. Methodological quality was assessed using appropriate critical appraisal tools according to study design. Because of substantial heterogeneity in study designs, populations, analytical platforms, dietary assessments, and cognitive measures, findings were synthesized qualitatively through an integrative approach.

Results: Thirty-seven studies met the eligibility criteria. Recurrent metabolic signatures associated with cognitive performance involved polyunsaturated fatty acids, phospholipids, sphingolipids, amino acids, and gut microbiota-derived metabolites. Diets rich in omega-3 fatty acids, polyphenols, and plant-based foods were generally associated with favorable metabolic profiles and better cognitive outcomes. Conversely, Western dietary patterns were more frequently linked to pro-inflammatory and potentially neurotoxic metabolite signatures. Lipid metabolism, oxidative stress, and neuroinflammatory pathways were the most consistently reported mechanisms.

Conclusions: Available evidence suggests that nutrition-related metabolic pathways are associated with cognitive health and may support the identification of biomarkers for cognitive decline. Nevertheless, methodological heterogeneity limits comparability and causal interpretation. Standardized analytical procedures, longitudinal designs, and multi-omics integration are needed to improve reproducibility and translational relevance.