Novel alkylresorcinol metabolites in human urine as potential exposure biomarkers for whole grain wheat and rye intake (270.6)

Abstract

Biomarkers of dietary intake are prominent tools in nutritional research. Alkylresorcinol (AR) metabolites, 3,5‐dihydroxybenzoic acid (3,5‐DHBA) and 3‐(3,5‐dihydroxyphenyl)propanoic acid (3,5‐DHPPA), have been proposed as exposure biomarkers of whole grain (WG) wheat and rye intake. However, the profile of AR metabolites is not fully understood. The aim of this study was to investigate the metabolism of ARs in mice and in humans, while further determining urinary pharmacokinetics of the novel AR metabolites to explore their potential as biomarkers of WG wheat intake. Utilization of LC‐MS approach resulted in ten AR metabolites (1‐10) identified in mice and in humans, including three phenolic acids and seven of their phase II conjugates. Among them, two novel metabolites were discovered, 5‐(3,5‐dihydroxyphenyl)pentanoic acid (3,5‐DHPPTA) and 2‐(3,5‐dihydroxybenzamido)acetic acid (3,5‐DHBA glycine). The structures of these two metabolites were confirmed by comparing with authentic standards synthesized in house. In the pharmacokinetic study, a group of twelve volunteers followed a polyphenolic restricted diet for 4 d before ingesting WG wheat bread containing 61mg ARs. Urine samples were collected for 32 h, and AR metabolites were quantified with HPLC‐CEAD. The mean urinary excretion rates and mean t1/2 of 3,5‐DHPPTA, 3,5‐DHBA glycine, 3,5‐DHBA and 3,5‐DHPPA at each time point were determined. Our results suggest that 3,5‐DHPPTA and 3,5‐DHBA glycine may be utilized in combination with 3,5‐DHBA and 3,5‐DHPPA as potential biomarkers to increase the accuracy of recording WG wheat and rye intake in epidemiologic studies. Further validation of 3,5‐DHPPTA and 3,5‐DHBA glycine as potential biomarkers is warranted. Grant Funding Source: 1This work was partially supported by funding from USDA‐NIFA grant 2012‐38821‐20012 to S. Sang.