Alkylresorcinol metabolites in urine and plasma as potential biomarkers of rye and wheat fiber consumption in prostate cancer patients and controls.

Alkylresorcinols (ARs) are phytochemicals mainly associated with rye/wheat bran. Plasma ARs and their plasma and urine metabolites are considered as biomarkers for whole-grain rye/wheat intake. However ARs metabolite day and night variations have not been studied in prostate cancer patients yet. We investigated ARs metabolites 3, 5-dihydroxy-benzoic acid (DHBA), and 3-(3, 5-dihydroxyphenyl)-1-propanoic acid (DHPPA) in urine and plasma in prostate cancer patients and in control group. DHPPA in 12-h overnight urine correlated with the intake of rye bread and bread fiber across short time periods (3 days). Plasma DHPPA concentration was significantly greater in the prostate cancer group than in the control group. DHPPA and DHBA excretion was significantly higher in the overnight urine than in day urine in the prostate cancer group but not in the control group. DHPPA concentration in plasma in the prostate cancer group did not depend on the intake of rye bread in the previous day, suggesting an impaired metabolism of ARs metabolites in the prostate cancer group. The results of this study suggest DHPPA in 12-h overnight urine as a biomarker to estimate the intake of rye bread and bread fiber.

Dietary intake and major sources of plant lignans in Latvian men and women.

Higher intake of lignans, diphenolic plant compounds, may reduce the risk of certain types of cancer and cardiovascular diseases. We assessed the dietary intake of four lignans: matairesinol, secoisolariciresinol, lariciresinol and pinoresinol. Furthermore, for the breads we supplemented the data with two more lignans: syringaresinol and medioresinol. Study subjects were 172 men and 97 women aged 40-75 years, residing in Riga, the capital of Latvia, all living at home, eating habitual food. Median total lignan intake was 2259 (range 1169-5759) µg/day. Secoisolariciresinol contributed 58% and syringaresinol 22% of lignan intake. Bread was the major food source of lignans in men (86%), whereas in women it was bread (57%) and flaxseed (35%).

Pharmacokinetics of alkylresorcinol metabolites in human urine.

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 curve0-25 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.

Polyketide derivatives active against Botrytis cinerea in Gerbera hybrida.

A previously isolated cDNA molecule from Gerbera hybrida (Asteraceae) codes for a new chalcone synthase-like polyketide synthase, 2-pyrone synthase (2PS). 2PS is able to synthesise 4-hydroxy-6-methyl-2-pyrone (triacetolactone), a putative precursor for gerberin and parasorboside, two abundant glucosides in gerbera. In this study, we show that gerbera plants transformed with the gene for 2PS in an antisense orientation and unable to synthesise gerberin and parasorboside are susceptible to Botrytis cinerea infection. In addition to the preformed glucosides, the transgenic plants also lack several compounds that are induced in control plants when infected with the mould. Some of these induced substances are effective in inhibiting fungal growth both in vitro and in vivo. Two of the phytoalexins were identified as the aglycones of gerberin and trans-parasorboside. The third phytoalexin is a rare coumarin, 4-hydroxy-5-methylcoumarin; however, it is typical of many plants of the sunflower family Asteraceae. The coumarin cannot be structurally derived from either gerberin or parasorboside, but may be derived from a related polyketide intermediate.

Plasma pharmacokinetics of alkylresorcinol metabolites: new candidate biomarkers for whole-grain rye and wheat intake.

BACKGROUND: Alkylresorcinols are phenolic compounds that are present almost exclusively in rye and wheat fiber. Alkylresorcinols are absorbed and thereafter metabolized to 3,5-dihydroxybenzoic acid (DHBA) and 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA), which have been detected in human urine and plasma. OBJECTIVE: The objective was to determine the plasma pharmacokinetics of DHBA and DHPPA in human subjects to estimate whether they show potential as biomarkers for whole-grain rye and/or wheat intake. DESIGN: Fifteen human volunteers followed a low-alkylresorcinol diet for 2 d before ingesting a single dose of high-fiber rye bread containing 100 mg alkylresorcinols [corrected]. Plasma samples were collected for 25 h, and the alkylresorcinol metabolites were quantified by HPLC with coulometric electrode array detection. RESULTS: Maximum concentrations were reached at approximately 6 h for both metabolites, although interindividual variation was found. The half-life was significantly (P < 0.0002) longer for DHPPA (16.3 h) than for DHBA (10.1 h). No significant differences were discovered between women and men in the half-life of each metabolite, which, from a pharmacokinetic point of view, is the most important parameter. The area under the curve differed significantly between DHBA and DHPPA (P < 0.0001) and between women and men (P = 0.03 for DHBA and P = 0.01 for DHPPA). However, when corrected for body weight, the difference between sexes was no longer significant. CONCLUSIONS: 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.