title: Dose response of whole-grain biomarkers: alkylresorcinols in human plasma and their metabolites in urine in relation to intake.
abstract: BACKGROUND
  Alkylresorcinols (ARs), phenolic lipids almost exclusively present in the outer parts of wheat and rye grains in commonly consumed foods, have been proposed as specific dietary biomarkers of whole-grain wheat and rye intakes.
  
  
  OBJECTIVE
  The objective was to assess the dose response of plasma ARs and the excretion of 2 recently discovered AR metabolites in 24-h urine samples in relation to AR intake and to establish a pharmacokinetic model for predicting plasma AR concentration.
  
  
  METHODS
  Sixteen subjects were given rye bran flakes containing 11, 22, or 44 mg total ARs 3 times daily during week-long intervention periods separated by 1-wk washout periods in a nonblinded randomized crossover design. Blood samples were collected at baseline, after the 1-wk run-in period, and after each treatment and washout period. Two 24-h urine samples were collected at baseline and after each treatment period.
  
  
  RESULTS
  Plasma AR concentrations and daily excretion of 2 urinary AR metabolites increased with increasing AR dose (P < 0.001). Recovery of urinary metabolites in 24-h samples decreased with increasing doses from approximately 90% to approximately 45% in the range tested. A one-compartment model with 2 absorption compartments with different lag times and absorption rate constants adequately predicted plasma AR concentrations at the end of each intervention period.
  
  
  CONCLUSIONS
  Both plasma AR concentrations and urinary metabolites in 24-h samples showed a dose-response relation to increased AR intake, which strongly supports the hypothesis that ARs and their metabolites may be useful as biomarkers of whole-grain wheat and rye intakes.
authors.affiliation: Department of Food Science, Swedish University of Agriculture Science, Uppsala, Sweden. rikard.landberg@lmv.slu.se
authors.forename: Rikard
authors.initials: R
authors.lastname: Landberg
authors.forename: Per
authors.initials: P
authors.lastname: Aman
authors.forename: Lena E
authors.initials: LE
authors.lastname: Friberg
authors.forename: Bengt
authors.initials: B
authors.lastname: Vessby
authors.forename: Herman
authors.initials: H
authors.lastname: Adlercreutz
authors.forename: Afaf
authors.initials: A
authors.lastname: Kamal-Eldin
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000652:urine; D003404:Creatinine / Q000652:urine; D018592:Cross-Over Studies; D004032:Diet; D004043:Dietary Fiber / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior; D005260:Female; D006801:Humans; D008297:Male; D010349:Patient Compliance; D012118:Resorcinols / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D012434:Secale / Q000737:chemistry*; D014908:Triticum / Q000737:chemistry*
chemical_list: D015415:Biomarkers; D004043:Dietary Fiber; D012118:Resorcinols; D003404:Creatinine