Abstract B99: Determinants of aspirin metabolism in healthy individuals
Authors: Navarro Sandi L. , Saracino Misty R. , Makar Karen W. , Thomas Sushma S. , Li Lin , Zheng Yingye , Levy Lisa , Schwarz Yvonne , Bigler Jeannette , Potter John D. , Lampe Johanna W. 
Published: May 2012

Regular use of aspirin is associated with lower colon cancer risk. High inter-individual variation in aspirin metabolism has been attributed to several factors, including sex, concomitant use of other drugs or alcohol, urine pH, ethnicity, and variants in metabolizing enzymes involved in glucuronidation of aspirin metabolites [i.e., UDP glucuronosyltransferases (UGT)]. However, little is known about the impact of other exposures, including dietary factors. Dietary constituents of citrus fruits, cruciferous vegetables and soy have been shown to induce UGT. Higher intakes may alter UGT activity and affect the ratio of aspirin metabolites excreted.

We evaluated, cross-sectionally, whether urinary excretion of aspirin [ASA] and its metabolites (salicylic acid [SA], salicyluric acid [SUA], salicyluric phonolic glucuronide [SUPG], salicyl acyl and phenolic acid glucuronides [SAG/SPG]) differed by UGT1A6 genotype and dietary factors. Following an oral dose of 650 mg aspirin, healthy men (N=264) and women (N=264), 20–40 years, collected urine over an 8-h period. Participant exclusion criteria included medical history of gastrointestinal, hepatic or renal disorders, and exposure to non-dietary factors known to influence biotransformation enzymes, e.g., medications, excessive alcohol, and smoking. FFQ data were available for 481 participants. Multiple linear regression was used to determine whether there were differences in aspirin metabolism by UGT1A6 genotype, or daily intake of protein, total fruit or vegetable intake, and soy, citrus and cruciferous vegetable intake, adjusted for body mass index (BMI), age, sex, ethnicity, urine volume and pH, and energy intake.

There were statistically significant differences in the ratios of metabolites excreted, (specific metabolite/sum of metabolites), between sexes and between ethnic groups. Men excreted more SUA (P&lt;0.001), and women excreted more SA and the glucuronides SAG/SPG (P≤0.001 for all 3). Compared to Caucasians, Asians excreted significantly more ASA, SA and SAG, and less SUA and SUPG (P≤0.03 for all), and African Americans excreted significantly more combined SAG/SPG, and less SUA (P≤0.04 for both). The interaction term for sex*ethnicity was significant for SUPG (P=0.006), with Caucasian men excreting the most, and Asian women excreting the least. Excretion of urinary aspirin metabolites did not differ statistically significantly between UGT1A6 genotypes (UGT1A6 *1/*1, *1/*2, and *2/*2). Increased ASA and decreased SUPG excretion was observed with increased servings of total vegetables (P=0.008 for both), and a trend toward significance with intake of cruciferous vegetables specifically (P=0.05 for both). A corresponding increase in SAG/SPG glucuronides was observed, but was not significant (P=0.40). There were no significant differences in metabolite excretion by soy or citrus fruit intake.

Of the factors evaluated, ethnicity and sex were the greatest, albeit modest, contributors to variability in aspirin metabolism (R2=2−13%), whereas UGT1A6 had no effect. Our results also suggest that diet may influence aspirin metabolism, but the effects do not appear to be via glucuronidation.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):B99.