Plasma hippuric acid as a marker of frailty influenced by dietary fruit and vegetable consumption: longitudinal analysis in Italian cohorts of older adults

Frailty is a geriatric syndrome characterised by loss of function and increased risk of death. Identification of individuals at risk of frailty is crucial for effective preventive interventions. This study aimed to investigate the association between plasma hippuric acid concentrations and frailty across two longitudinal Italian cohorts. Plasma hippuric acid was quantified using European Medicines Agency-validated mass spectrometry methods in plasma samples from InCHIANTI ( n = 534; 55.4% females; aged ≥65 years, 1998, 2002, 2004, 2008 follow-ups, FU) and InveCe.Ab ( n = 912; 53.8% females; aged ≥70 years, 2010, 2012, 2014, 2018 FU) participants who were non-frail at baseline. Frailty was defined through two different classifications: frailty index (FI) and frailty phenotype (FP). Longitudinal association between hippuric acid and frailty indexes within the two cohorts was assessed by linear mixed models adjusting for sex, age, educational status, renal and liver function, and body mass index. Mediation analyses explored the role of hippuric acid in mediating the fruit and vegetable consumption-frailty relationship. Median values of hippuric acid concentrations were significantly lower in frail compared to non-frail participants (measured by FI) in both (i) InCHIANTI study: non-frail = 1.59 (Q 1 –Q 3 , 0.99–2.74) μg/ml vs frail = 1.18 (0.75–1.88) (μg/mL in 2004 year FU; non-frail = 1.44 (0.87–2.50) μg/ml vs frail = 1.12 (0.63–1.99) μg/ml in 2007 year FU; and (ii) InveCe.Ab study: non-frail = 2.19 (1.26–3.92) μg/ml vs frail = 1.81 (0.87–3.65) μg/ml in 2018 year FU. No statistically significant cross-sectional associations were observed between hippuric acid and FP. Longitudinal association showed that higher plasma hippuric acid levels were significantly associated with a reduced risk of frailty ( p = 0.026 InCHIANTI and p = 0.044 InveCe.Ab). Longitudinal mediation analysis indicated that hippuric acid act as mediator of the relationship between fruit and vegetable intake and FI ( p < 0.05) in both cohorts. Low plasma hippuric acid levels may serve as a marker of frailty, potentially linked to reduced fruit and vegetable intake.