Human Nutrition Unit, Department of Food & Drug, University of Parma, Parma, Italy.
Food Funct. 2020 May 1;11(5):3975-3985. doi: 10.1039/d0fo00806k. Epub 2020 May 12.
Cranberries are a rich source of poly(phenols), mainly monomeric and oligomeric flavan-3-ols. However, information on the appearance of their main circulating microbial metabolites, namely phenyl-γ-valerolactones and phenylvaleric acid, is lacking despite its relevance to understanding the health effects attributed to cranberries. The aim of this study was to evaluate the absorption, metabolism and urinary excretion of cranberry flavan-3-ols through the targeted analysis of phenyl-γ-valerolactones and their related phenylvaleric acids, considering also their potential as biomarkers of flavan-3-ol intake and inter-individual variability in their appearance in plasma and urine. A six-arm acute crossover, randomized, double-blinded, controlled intervention trial was performed in ten healthy males who consumed a cranberry juice drink (375, 716, 1131, 1396, 1741 mg of total flavan-3-ols) or an isocaloric control drink with one-week washout. Plasma and urine were analyzed by UHPLC-ESI-QqQ-MS/MS and 22 compounds were identified. Glucuronide and sulfate conjugates of 5-(3',4'-dihydroxyphenyl)-γ-valerolactone were the main circulating and excreted metabolites after cranberry juice intake, with glucuronidation appearing to be the most favorable conjugation route. These compounds reached maximum plasma concentration at about 4-6 h. Plasma and urinary concentrations of the sum of the metabolites increased in relation to the amounts of cranberry flavan-3-ols provided by the drink, showing a clear and linear dose-dependent relationship and underscoring their potential as biomarkers of flavan-3-ol intake. A high inter-individual variability in circulating and urinary metabolite levels was observed and, interestingly, some subjects seemed to display a greater efficiency in metabolizing flavan-3-ols and producing phenyl-γ-valerolactones.
蔓越莓富含多酚，主要为单体和低聚黄烷-3-醇。然而，尽管了解蔓越莓对健康的影响与蔓越莓主要循环微生物代谢产物，即苯基-γ-戊内酯和苯丙酸的出现有关，但有关这些物质的信息仍然缺乏。本研究旨在通过靶向分析苯基-γ-戊内酯及其相关的苯丙酸，评估蔓越莓黄烷-3-醇的吸收、代谢和尿排泄情况，同时考虑其作为黄烷-3-醇摄入量的生物标志物和个体间差异在其出现在血浆和尿液中的可能性。在 10 名健康男性中进行了六臂急性交叉、随机、双盲、对照干预试验，这些男性饮用了蔓越莓汁（375、716、1131、1396、1741mg 总黄烷-3-醇）或具有相同热量的对照饮料，洗脱期为一周。采用 UHPLC-ESI-QqQ-MS/MS 分析血浆和尿液，鉴定出 22 种化合物。5-（3'，4'-二羟基苯基）-γ-戊内酯的葡萄糖醛酸和硫酸盐缀合物是蔓越莓汁摄入后主要的循环和排泄代谢物，葡萄糖醛酸化似乎是最有利的结合途径。这些化合物在饮用蔓越莓汁后约 4-6 小时达到血浆最大浓度。随着饮料提供的蔓越莓黄烷-3-醇量的增加，代谢物的总和在血浆和尿液中的浓度增加，显示出清晰的线性剂量依赖性关系，强调了它们作为黄烷-3-醇摄入量生物标志物的潜力。观察到循环和尿液代谢物水平的个体间变异性很大，有趣的是，一些受试者似乎在代谢黄烷-3-醇和产生苯基-γ-戊内酯方面效率更高。
