Association between caffeine metabolites in urine and muscle strength in young and older adults: A cross-sectional study from NHANES 2011–2012

Background Elevated levels of reactive oxygen species may contribute to the gradual decline in muscle strength over time. Although caffeine and its metabolites have antioxidant properties that can mitigate oxidative stress, the association of caffeine and its metabolites with muscle strength remains unknown. Aim To investigate whether caffeine metabolites in urine are associated with muscle strength in young and older adults. Methods A cross-sectional study was conducted with 1145 individuals aged over 20 years (n=801 < 60 years and n=344 ≥ 60 years) from the National Health and Nutrition Examination Survey (NHANES) 2011 – 2012. Muscle strength was assessed using a handgrip dynamometer, and combined grip strength was determined by summing the highest value from each hand. Caffeine and its metabolites in urine were quantified using ultra-high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (1-methyluric acid, 3-methyluric acid, 7-methyluric acid, 1,3-dimethyluric acid, 1,7-dimethyluric acid, 3,7-dimethyluric acid, 1,3,7-trimethyluric acid, 1-methylxanthine, 3-methylxanthine, 7-methylxanthine, 1,3-dimethylxanthine, 1,7-dimethylxanthine, 3,7-dimethylxanthine, 1,3,7-trimethylxanthine, 5-acetylamino-6-amino-3-methyluracil). Linear regression analyses were performed to determine the association of caffeine and its metabolites with muscle strength in young and older adults, adjusting for confounders. Results Positive associations between muscle strength and levels of 7-methyluric acid (β = 0.029; p = 0.021), 1,3-dimethyluric acid (β = 0.008; p = 0.004), 3,7-dimethyluric acid (β = 0.645; p = 0.012), 3-methylxanthine (β = 0.020; p = 0.002), 7-methylxanthine (β = 0.029; p = 0.006), 1,3-dimethylxanthine (theophylline) (β = 0.030; p = 0.004) and 3,7-dimethylxanthine (theobromine) (β = 0.035; p = 0.029) were observed in older adults. In contrast, no such associations were noted in young adults. Conclusion Our study indicates a positive association between certain caffeine metabolites in urine and muscle strength in older adults, but not in younger individuals. These findings indicate that specific caffeine metabolites may contribute to an antioxidant role especially in older adults.