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Dose response of whole-grain biomarkers: alkylresorcinols in human plasma and their metabolites in urine in relation to intake^1,2,3

¹ From the Department of Food Science, Swedish University of Agriculture Science, Uppsala, Sweden (RL, PÅ, and AK-E); the Department of Pharmaceutical Biosciences, Division of Pharmacokinetics and Drug Therapy, University of Uppsala, Uppsala, Sweden (LEF); the Department of Public Health & Caring Science and Geriatrics, Unit of Clinical Nutrition and Metabolism, University of Uppsala, Uppsala, Sweden (BV); and the Institute for Preventive Medicine, Nutrition and Cancer, Folkhälsan Research Center and Department of Clinical Chemistry, University of Helsinki, Helsinki, Finland (HA).

² Supported by the Swedish Governmental Agency for Innovation Systems; the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning; the Swedish Nutrition Foundation; the Richard and Stina Högbergs Foundation; and the Sigrid Jusélius Foundation, Helsinki, Finland. The rye bran flakes were kindly provided by Lantmännen AB.

³ Reprints not available. Address correspondence to R Landberg, Department of Food Science, Swedish University of Agriculture Science, Box 7051, SE-75007, Uppsala, Sweden. E-mail: rikard.landberg{at}lmv.slu.se.

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.

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				R. Landberg, A. Kamal-Eldin, S.-O. Andersson, J.-E. Johansson, J.-X. Zhang, G. Hallmans, and P. Aman Reproducibility of Plasma Alkylresorcinols during a 6-Week Rye Intervention Study in Men with Prostate Cancer J. Nutr., May 1, 2009; 139(5): 975 - 980. [Abstract] [Full Text] [PDF]