Estimating dietary caffeine exposure and CYP1A2, NAT2 and XO enzyme function by urinary caffeine metabolite biomonitoring: a pilot study.

Epidemiologic studies almost exclusively use food frequency reporting for assessing caffeine consumption. Major dietary caffeine sources, such as coffee and tea, are difficult to standardize for caffeine content due to their inherent heterogeneity. In this pilot study the determination of urinary caffeine and 15 metabolites was explored as a means of assessing caffeine exposure. Measurements were also used to investigate the identification of CYP1A2, NAT2 and XO activity phenotypes using uncontrolled caffeine exposure. Multiple spot urine samples were collected from volunteers over a period of one week during which food diaries were maintained. Urinary caffeine and metabolites were quantified by normal‐phase HPLC with UV‐visible absorbance detection. Using this approach, 13 of 15 metabolites were chromatographically resolved. Significant (p ≥ 0.05) associations between caffeine consumption estimated from food diaries and urinary caffeine and 1,7‐dimethyluric acid levels were observed. Using metabolite ratios proposed in the scientific literature, CYP1A2, NAT2 and XO enzyme activity phenotypes could be determined for all subjects. Though intra‐week variation in these ratios was observed in all subjects, in most cases the values remained within a given phenotype category. These results are promising for the future development of caffeine exposure and enzyme activity biomonitoring protocols.