Metabolomic profiles of dietary exposure associated with frailty in older adults: A systematic review.

Frailty is defined by the World Health Organization as a state of increased vulnerability in older adults, characterized by a decline in physiological functions across multiple systems and heightened sensitivity to external stressors. The global prevalence of frailty is expected to rise due to population ageing, highlighting the need for effective preventive strategies. However, while diet can play a crucial role in this context, their relationship is complex and potentially bidirectional: unhealthy dietary patterns may contribute to the onset of frailty, whereas early stages of frailty may influence food choices through limitations in meal preparation, and appetite. Hence, identifying biomarkers associated with frailty phenotypes may help clarify these mechanisms and improve prevention strategies. This systematic review aims to summarize current evidence on metabolomics-derived biomarkers potentially involved in the relationship between dietary patterns and frailty. A comprehensive literature search was conducted across three electronic databases (PubMed, Web of Science, Scopus) in accordance with the PRISMA guidelines, yielding 1661 studies, of which five met the inclusion criteria. Three dietary exposures were identified and analyzed: fruit and vegetable, plant/animal protein intake, and adherence to the Mediterranean diet. The findings suggest that specific metabolites, such as hippuric acid, different amino acids, and lipid derived compounds may represent potential candidates for establishing a metabolic signature of frailty. Nevertheless, current evidence remains limited and unclear about the direction of associations. Further research is needed, particularly in healthy populations, to validate the effectiveness of these biomarkers, and tailor guidelines specific for older adults.