Determinants of aspirin metabolism in healthy men and women: effects of dietary inducers of UDP-glucuronosyltransferases

J Nutrigenet Nutrigenomics. 2011;4(2):110-8. doi: 10.1159/000327782. Epub 2011 May 28.

Abstract

Background/aims: Interindividual variation in aspirin (ASA) metabolism is attributed to concomitant use of drugs or alcohol, urine pH, ethnicity, sex, and genetic variants in UDP-glucuronosyltransferases (UGT). Little is known about the effects of diet.

Methods: We evaluated cross-sectionally whether urinary excretion of ASA and its metabolites [salicylic acid (SA), salicyluric acid (SUA) phenolic glucuronide (SUAPG), salicylic acid acyl glucuronide (SAAG) and salicylic acid phenolic glucuronide (SAPG)] differed by UGT1A6 genotype and dietary factors shown to induce UGT. Following oral treatment with 650 mg ASA, urine was collected over 8 h in 264 men and 264 women (21-45 years old).

Results: There were statistically significant differences in metabolites excreted between sexes and ethnicities. Men excreted more SUA; women more ASA (p = 0.03), SA, SAAG and SAPG (p ≤ 0.001 for all). Compared to Caucasians, Asians excreted more ASA, SA and SAAG, and less SUA and SUAPG (p ≤ 0.03 for all); African-Americans excreted more SAAG and SAPG and less SUA (p ≤ 0.04). There was no effect of UGT1A6 genotypes. Increased ASA and decreased SUAPG excretion was observed with increased servings of vegetables (p = 0.008), specifically crucifers (p = 0.05).

Conclusion: Diet may influence the pharmacokinetics of ASA, but effects may be through modulation of glycine conjugation rather than glucuronidation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aspirin / administration & dosage
  • Aspirin / metabolism*
  • Aspirin / pharmacokinetics
  • Cross-Sectional Studies
  • Diet*
  • Enzyme Induction
  • Ethnicity
  • Female
  • Genetic Association Studies
  • Glucuronides / metabolism
  • Glucuronosyltransferase / biosynthesis*
  • Glucuronosyltransferase / genetics
  • Glycine / metabolism
  • Humans
  • Male
  • Middle Aged
  • Nutrigenomics
  • Sex Characteristics
  • Young Adult

Substances

  • Glucuronides
  • UDP-glucuronosyltransferase, UGT1A6
  • Glucuronosyltransferase
  • Aspirin
  • Glycine