Objectives: To evaluate for the first time the longitudinal relationship between serum uric acid concentrations and risk of frailty.

Methods: Prospective cohort study of 2198 non-institutionalized individuals aged ≥60years recruited in 2008-2010. At baseline, information was obtained on socio-demographic factors, health behaviors and morbidity, while serum uric acid was determined in 12-h fasting blood samples. Study participants were followed-up through 2012 to assess incident frailty, defined as ≥2 of the following 4 Fried criteria: exhaustion, muscle weakness, low physical activity, and slow walking speed.

Results: During a mean 3.5-year follow-up, 256 cases of incident frailty were identified. After multivariate adjustment, the odds ratios (95% confidence interval) of frailty comparing the second and third tertiles of uric acid to the lowest tertile were, respectively: 1.18 (0.83-1.68) and 1.57 (1.11-2.22); p-linear trend=0.01. The corresponding result for a 1mg/dL increase in serum uric acid concentration was 1.12 (1.00-1.24). Similar associations were observed across subgroups defined by sex, age, body mass index, and physical activity. As regards each frailty component, the odds ratios (95% confidence interval) per 1mg/dL increase in serum uric acid were 1.10 (0.99-1.23) for low physical activity, 1.08 (0.95-1.23) for low walking speed, 1.08 (0.67-1.73) for exhaustion and 0.91 (0.81-1.02) for weakness.

Conclusions: Serum uric acid concentrations are positively associated with the risk of frailty in older adults. Further studies are needed to evaluate whether specific dietary recommendations or pharmacological strategies aimed at lowering serum uric acid would be beneficial to prevent the development of this syndrome.