Plasmatic Hippuric Acid as a Hallmark of Frailty in an Italian Cohort: The Mediation Effect of Fruit–Vegetable Intake

Frailty syndrome is an age-related condition involving a loss of resilience, susceptibility to adverse health outcomes, and poor quality of life. This study was conducted in the framework of InveCe.Ab, an ongoing longitudinal population-based study. Plasma from 130 older individuals (older adults aged 76–78 years) was analyzed and validated (on 303 participants) using mass spectrometry-based metabolomics approaches. Equivalence tests showed that metabolites from the central cellular metabolic pathways were equivalent in frail and fit participants. Hippuric acid was the only cometabolite that distinguished fit from frail older adults. Logistic regression analysis indicated that high hippuric acid levels are significantly associated with a reduction of the risk of frailty after 4 years. Mediation analysis using a Frailty Index, hippuric acid, and fruit–vegetable intake supported the role of fruit–vegetable consumption in the hippuric acid relationship with the Frailty Index. These data point to low plasma hippuric acid as a plausible hallmark of frailty status, associated with lower fruit–vegetable intakes.