Pharmacokinetics of alkylresorcinol metabolites in human urine

Abstract

Wholegrain cereals are reported to promote beneficial health effects. Wholegrain wheat and rye are almost exclusive sources of alkylresorcinols, and intact alkylresorcinols together with their plasma and urinary metabolites, 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA) and 3,5-dihydroxybenzoic acid (DHBA), have been proposed as biomarkers of the intake of these foods in humans. The pharmacokinetics of alkylresorcinols and their metabolites in plasma have been determined but not that of the urinary metabolites. We aimed to characterise the urinary pharmacokinetics of alkylresorcinol metabolites in humans to evaluate their potential as biomarkers of wholegrain wheat and rye. A group of fifteen volunteers followed a low-alkylresorcinol diet for 2 d before ingesting a single dose of rye bread, containing 100 mg alkylresorcinols. Urine was collected between baseline (0 h) and 25 h after administration. Thereafter alkylresorcinol metabolites were quantified by HPLC with coulometric electrode array detection. Maximum excretion rates were observed at 5-6 h for both metabolites, DHPPA being predominant over DHBA and also possessing a greater area under the curve 0 -25 h . Total urinary recovery between 0 and 25 h yielded 43 % of ingested alkylresorcinols, and at 25 h significant amounts of metabolites were still retained in the body, suggesting that even a spot urine sample may be sufficient to indicate whether or not wholegrain wheat or rye is a daily dietary component. These results support the use of urinary DHPPA and DHBA as biomarkers of wholegrain wheat and rye and enable new potential for studying the association between wholegrain intake and diseases, even in the absence of dietary data.

Alkylresorcinol Metabolites in Urine and Plasma as Potential Biomarkers of Rye and Wheat Fiber Consumption in Prostate Cancer Patients and Controls

“…A previous study showed that AR metabolites excretion is lower during the night: DHPPA and DHBA excretion rates in overnight urine were found to be lower than in day urine in healthy participants (16). We also found that participants of the PC group had significantly greater concentrations of DHPPA and DHBA in 12-h overnight urine than in 12-h day urine.…”

“…Both free and conjugated forms (glucuronide or sulfate) of the metabolites are present in urine and plasma. DHPPA usually peaks first in urine and later in plasma (13,16), while DHBA peaks simultaneously in urine and plasma. DHPPA peaking earlier in urine than in plasma could presumably be explained by its higher glucuronization rate than that for DHBA, as reported recently (21).…”

“…The averages of 3DFR data and the data obtained on the third day of food record were analyzed separately. This was done to get more precise data about the relation between the dietary data and plasma/urinary AR metabolites, considering that the t1/2 for DHPPA in plasma is 16.3 h (13) whereas those in urine are 11.9 h for DHPPA and 9.9 h for DHBA (16). On the third day of the food record, participants collected samples of their 12-h day and 12-h overnight urine.…”

“…In urine, the intact ARs have been identified only in minor amounts after extremely high intake (15). However, DHPPA and DHBA may serve as urinary biomarkers with higher concentrations and longer mean excretion time (11.9 and 9.9 h, respectively) (16). The status of plasma and urine DHPPA and DHBA as biomarkers of the whole grain rye/wheat intake is still largely unknown, and more human data are needed on metabolism and excretion of ARs.…”

Alkylresorcinol Metabolite Concentrations in Spot Urine Samples Correlated with Whole Grain and Cereal Fiber Intake but Showed Low to Modest Reproducibility over One to Three Years in U.S. Women

“…Recently, 2 main metabolites of AR 3,5-dihydroxybenzoic acid (DHBA) and 3-(3,5-dihydroxyphenyl)-1-propionic acid (DHPPA) showed longer apparent half-lives compared with intact AR homologs (16,17). The longest apparent half-life was observed for DHPPA (12 h), suggesting that it may better reflect more long-term WG intake (17).…”