Association between caffeine metabolites in urine and serum uric acid levels: a cross-sectional study from NHANES 2011 to 2012

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 1252 individuals aged 20-80 years. The study assessed caffeine and fourteen metabolites in spot urine samples, as well as serum UA levels. Hyperuricaemia 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 hyperuricaemia. In linear regression analyses, paraxanthine (<i>β</i> = -0·004, <i>P</i> = 0·006), theobromine (<i>β</i> = -0·004, <i>P</i> =< 0·001), 7-methyluric acid (<i>β</i> = -0·003, <i>P</i> = 0·003), 3,7-dimethyluric acid (<i>β</i> = -0·029, <i>P</i> = 0·024), 3-methylxanthine (<i>β</i> = -0·001, <i>P</i> = 0·038) and 7-methylxanthine (<i>β</i> = -0·001, <i>P</i> = 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.