Urinary 3,3'-diindolylmethane: a biomarker of glucobrassicin exposure and indole-3-carbinol uptake in humans

Cancer Epidemiol Biomarkers Prev. 2014 Feb;23(2):282-7. doi: 10.1158/1055-9965.EPI-13-0645. Epub 2013 Dec 19.

Abstract

Background: Brassica vegetable consumption may confer a protective effect against cancer, possibly attributable to their glucosinolates. Glucobrassicin is a predominant glucosinolate and is the precursor of indole-3-carbinol (I3C), a compound with anticancer effects. However, objective assessments of I3C uptake from Brassica vegetables have not been successful.

Methods: We conducted a randomized, crossover trial to test whether 3,3'-diindolylmethane (DIM, a metabolite of I3C) excreted in the urine after consumption of raw Brassica vegetables with divergent glucobrassicin concentrations is a marker of I3C uptake from such foods. Twenty-five subjects were fed 50 g of either raw "Jade Cross" Brussels sprouts (high glucobrassicin concentration) or "Blue Dynasty" cabbage (low glucobrassicin concentration) once daily for 3 days. All urine was collected for 24 hours after vegetable consumption each day. After a washout period, subjects crossed over to the alternate vegetable. Urinary DIM was measured using a novel liquid chromatography-electrospray ionization-tandem mass spectrometry-selected reaction monitoring (LC-ESI-MS/MS-SRM) method with [(2)H2]DIM as internal standard.

Results: Urinary DIM was consistently and significantly higher after Brussels sprouts feeding than after cabbage feeding, as evidenced by an average difference of 8.73 pmol/mg creatinine (95% confidence interval, 5.36-12.10; P = 0.00002).

Conclusion: We have successfully quantified urinary DIM after uptake of I3C from food, and demonstrated that differences in glucobrassicin exposure are reflected in urinary DIM levels.

Impact: Our LC-ESI-MS/MS-SRM method and the results of our study indicate urinary DIM is a measure of I3C uptake from Brassica vegetables, a finding that can be utilized in prospective epidemiologic and chemoprevention studies.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / urine
  • Brassica*
  • Cross-Over Studies
  • Female
  • Glucosinolates / administration & dosage*
  • Glucosinolates / pharmacokinetics
  • Humans
  • Indoles / administration & dosage*
  • Indoles / pharmacokinetics*
  • Indoles / urine*
  • Male
  • Middle Aged
  • Tandem Mass Spectrometry
  • Young Adult

Substances

  • Biomarkers
  • Glucosinolates
  • Indoles
  • indole-3-carbinol
  • glucobrassicin
  • 3,3'-diindolylmethane