Metabolomic Profile of Different Dietary Patterns and Their Association with Frailty Index in Community-Dwelling Older Men and Women

Diet quality has been associated with slower rates of aging; however, the mechanisms underlying the role of a healthy diet in aging are not fully understood. To address this question, we aimed to identify plasma metabolomic biomarkers of dietary patterns and explored whether these metabolites mediate the relationship between diet and healthy aging, as assessed by the frailty index (FI) in 806 participants of the Baltimore Longitudinal Study of Aging. Adherence to different dietary patterns was evaluated using the Mediterranean diet score (MDS), Mediterranean–DASH Diet Intervention for Neurodegenerative Delay (MIND) score, and Alternate Healthy Eating Index-2010 (AHEI). Associations between diet, FI, and metabolites were assessed using linear regression models. Higher adherence to these dietary patterns was associated with lower FI. We found 236, 218, and 278 metabolites associated with the MDS, MIND, and AHEI, respectively, with 127 common metabolites, which included lipids, tri/di-glycerides, lyso/phosphatidylcholine, amino acids, bile acids, ceramides, cholesterol esters, fatty acids and acylcarnitines, indoles, and sphingomyelins. Metabolomic signatures of diet explained 28%, 37%, and 38% of the variance of the MDS, MIND, and AHEI, respectively. Signatures of MIND and AHEI mediated 55% and 61% of the association between each dietary pattern with FI, while the mediating effect of MDS signature was not statistically significant. The high number of metabolites associated with the different dietary patterns supports the notion of common mechanisms that underly the relationship between diet and frailty. The identification of multiple metabolite classes suggests that the effect of diet is complex and not mediated by any specific biomarkers. Furthermore, these metabolites may serve as biomarkers for poor diet quality to identify individuals for targeted dietary interventions.