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Published online by Cambridge University Press: 09 June 2025
Several studies have indicated a potential inverse association between caffeine intake from dietary sources—assessed through dietary questionnaires—and uric acid (UA) levels. However, to date, no study has examined the relationship between urinary caffeine metabolites, which serve as a reliable biomarker of caffeine intake, and UA levels. Our aim was to evaluate the association between caffeine metabolites in urine and serum UA levels. A cross-sectional study was conducted using data from the National Health and Nutrition Examination Survey (NHANES) 2011-2012, involving 1,252 individuals aged 20 to 80 years. The study assessed caffeine and 14 metabolites in spot urine samples, as well as serum UA levels. Hyperuricemia was defined as UA levels exceeding 7.0 mg/dL for men and 6.0 mg/dL for women. In logistic regression analyses, theobromine (OR: 0.99, 95% CI: 0.980 - 0.999), 3-methyluric acid (OR: 0.91, 95% CI: 0.837 - 0.996), 7-methyluric acid (OR: 0.99, 95% CI: 0.989 - 0.998), and 3-methylxanthine (OR: 0.99, 95% CI: 0.992 - 0.999) were associated with decreased odds of hyperuricemia. In linear regression analyses, paraxanthine (β = -0.004, p= 0.006), theobromine (β = -0.004, p= <0.001), 7-methyluric acid (β = -0.003, p= 0.003), 3,7-dimethyluric acid (β = -0.029, p= 0.024), 3-methylxanthine (β = -0.001, p= 0.038), and 7-methylxanthine (β = -0.001, p= 0.001) were inversely associated with serum UA levels. In conclusion, our results indicate that several urinary caffeine metabolites are inversely associated with UA levels. These findings should be interpreted with caution due to the small magnitude of the observed associations.