Alkylresorcinols (AR) could be good biomarkers of consumption of fiber-rich cereal products. The aim of this study was to examine the relationship between plasma ARs or urinary AR metabolites and cereal fiber intake in women consuming their habitual diet. Twenty-five postmenopausal and 31 premenopausal women were recruited. The subjects included also vegetarians (n = 20) to obtain a broad range of cereal intake. Dietary intake, plasma ARs, and urinary AR metabolites [3,5-dihydroxybenzoic acid and 3-(3,5-dihydroxyphenyl)-1-propanoic acid] were measured. Pearson's and Partial correlation tests were done between dietary fiber intake and plasma ARs or urinary AR metabolites. Cereal fiber intake correlated significantly with plasma AR C17:0 (r = 0.387), AR C19:0 (r = 0.350), AR C21:0 (r = 0.428), AR C23:0 (r = 0.409), AR C25:0 (r = 0.283), and total AR (r = 0.406) and with urinary AR metabolites DHBA (r = 0.359) and DHPPA (r = 0.402) even after adjustment for body mass index and age, which could be confounding variables. This is the first study to show a significant correlation between plasma ARs or urinary AR metabolites and cereal fiber intake during consumption of a habitual diet. These results indicate that assay of plasma ARs or urinary AR metabolites may be used as biomarkers in epidemiologic studies in free-living populations to evaluate the role of cereal fiber intake in various diseases. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2244 -8)

Background: Whole-grain rye and wheat cereals contain high amounts of alkylresorcinols (ARs), phenolic lipids. ARs can be quantified in plasma. Two recently identified urinary AR metabolites, 3,5-dihydroxyphenylbenzoic acid (DHBA) and 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA), may be useful as biomarkers of intake of whole-grain rye and wheat. Methods: We evaluated 4 pretreatment protocols for quantifying urinary DHBA and DHPPA using HPLC coupled with a coulometric electrode array detector. Syringic acid was used as the internal calibrator. Results: Measured urinary concentrations of DHBA and DHPPA were 0.8–115 μmol/L. The mean recoveries of all added concentrations were 85%–104% for DHBA and 86%–99% for DHPPA, depending on the degree of the purification. The protocol versions with less purification correlated well with the protocol including highest purification. The correlation coefficients (r2) were 0.9699–0.8153 for DHBA and 0.9854–0.8371 for DHPPA. Conclusion: Although the protocol with the most purification steps was most specific, all protocols were suitable for measuring DHBA and DHPPA in urine. The rapid protocol with simple hydrolysis could be used in large-scale clinical studies. Additional investigation is needed to clarify whether these metabolites are useful biomarkers of whole-grain intake and helpful in the exploration of its association with human diseases.

Our results suggest that DHBA and DHPPA are both good candidate biomarkers for whole-grain rye and/or wheat intake; however, DHPPA is the better indicator because of its longer half-life. This could provide a practical tool when investigating the association between diet and diseases.

5-n-Alkylresorcinols (AR) are a major group of phenolic compounds in whole-grain wheat, rye, and barley. As such, they may serve as potential biomarkers of whole-grain intake, because they are quantifiable intact in plasma and as metabolites in urine. We examined relationships between 12-h urinary excretion of AR metabolite 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA) and self-reported habitual intake of whole-grain foods measured by 3-d food record (3DFR) and FFQ. Urine samples from 100 men and women were analyzed for DHPPA using HPLC with coularray detection. DHPPA excretion ranged from 1.3 to 99.4 (mean +/- SE, 14.0 +/- 1.5) mumol/12 h. Whole-grain food intake, as determined by 3DFR and FFQ and adjusted for BMI and energy and fiber intake, was significantly associated with 12-h urinary DHPPA excretion. Based on 3DFR, whole-grain wheat + rye consumers had a 44% higher DHPPA excretion than nonconsumers [ratio of excretion (95% CI) = 1.44 (1.04, 1.97); P = 0.029]. Using whole-grain intake estimated by FFQ, a serving increase in whole-grain wheat + rye intake increased DHPPA excretion by 94% [ratio of excretion (95% CI) = 1.94 (1.35, 2.78); P = 0.001] and a serving increase in whole grains as defined more broadly in epidemiologic studies of whole-grain intake and disease risk (whole-grain wheat, rye, oats, and corn) increased DHPPA by 67% [ratio of excretion (95% CI) = 1.67 (1.28, 2.17); P < 0.0001]. This study supports the potential utility of urinary DHPPA as a biomarker of whole-grain intake in a U.S. population.

It has been demonstrated that intact plasma alkylresorcinols (AR) and urinary AR metabolites could be used as biomarkers of whole-grain intake. Thereafter, we developed the method for the plasma AR metabolites, which is more convenient and requires less sample pretreatment than the analysis of intact plasma AR. The aim of the present study is to evaluate whether AR metabolites measured in plasma, in the same population, could also be considered as useful biomarkers of cereal fibre. Fifty-six women were recruited in a cross-sectional and observational study. Dietary intake (5-d record) and plasma AR metabolites (3,5-dihydroxybenzoic acid, DHBA; 3-(3,5-dihydroxyphenyl)-1-propanoic acid, DHPPA) were measured. The relationship between plasma AR metabolites and cereal fibre intake was examined using partial correlation and stepwise regression. Cereal fibre intake correlated significantly with plasma DHBA (r 0·411; P¼ 0·002) and DHPPA (r 0·463; P¼ 0·000) even after adjustment for BMI and age. Thus, plasma AR metabolites correlate with cereal fibre intake as noted with plasma intact AR and urinary AR metabolites. We observed that plasma DHPPA was the independent predictor of cereal fibre intake, explaining 18 % of the variance (adjusted r 2 0·176; P¼ 0·002). In epidemiological screening, it might be easier to obtain and to collect plasma than urine samples. In addition, the plasma AR metabolites half-life seems longer than those of intact plasma AR, and their measurements are more convenient, and faster. Thus, sum of plasma AR metabolites and more specifically plasma DHPPA seems to be good and specific biomarkers of cereal fibre intake.