Dose response of whole-grain biomarkers: Alkylresorcinols in human plasma and their metabolites in urine in relation to intake

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. Design: 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 ≈90% to ≈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. Conclusion: 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.