Chair of Food Chemistry and Molecular Sensory Science, Technische Universität München, Lise-Meitner-Str 34, 85354, Freising, Germany.
Anal Bioanal Chem. 2013 Oct;405(26):8487-503. doi: 10.1007/s00216-013-7288-0. Epub 2013 Aug 28.
Habitual consumption of medium amounts of coffee over the whole life-span is hypothesized to reduce the risk to develop diabetes type 2 (DM2) and Alzheimer's disease (AD). To identify putative bioactive coffee-derived metabolites, first, pooled urine from coffee drinkers and non-coffee drinkers were screened by UPLC-HDMS. After statistical data analysis, trigonelline, dimethylxanthines and monomethylxanthines, and ferulic acid conjugates were identified as the major metabolites found after coffee consumption. For quantitative analysis of these markers in body fluids, targeted methods based on stable-isotope dilution and UPLC-MS/MS were developed and applied to plasma samples from a coffee intervention study (n = 13 volunteers) who consumed a single cup of caffeinated coffee brew after a 10-day washout period. Chlorogenic acid-derived metabolites were found to be separated into two groups showing different pharmacokinetic properties. The first group comprised, e.g., ferulic acid and feruloyl sulfate and showed early appearance in the plasma (~1 h). The second group contained particularly chlorogenic acid metabolites formed by the intestinal microflora, appearing late and persisting in the plasma (>6 h). Trigonelline appeared early but persisted with calculated half-life times ~5 h. The plasma levels of caffeine metabolites significantly and progressively increased 2-4 h after coffee consumption and did not reach c max within the time frame of the study. The pharmacokinetic profiles suggest that particularly trigonelline, caffeine, its metabolites, as well as late appearing dihydroferulic acid, feruloylglycine and dihydroferulic acid sulfate formed from chlorogenic acid by the intestinal microflora accumulate in the plasma due to their long half-life times during habitual consumption of several cups of coffee distributed over the day. Since some of these metabolites have been reported to show antioxidant effects in vivo, antioxidant-response-element activating potential, and neuroprotective properties, respectively, some of these key metabolites might account for the inflammation- and DM2/AD risk reducing effects reported for habitual life time consumption of coffee.
长期习惯性摄入适量咖啡被认为可降低 2 型糖尿病（DM2）和阿尔茨海默病（AD）的发病风险。为了鉴定潜在的咖啡衍生生物活性代谢物，首先通过 UPLC-HDMS 筛选了咖啡饮用者和非咖啡饮用者的混合尿液。经过统计学数据分析，鉴定出咖啡摄入后的主要代谢物为葫芦巴碱、二甲黄嘌呤和单甲基黄嘌呤，以及阿魏酸缀合物。为了对这些生物标志物在体液中的定量分析，开发并应用了基于稳定同位素稀释和 UPLC-MS/MS 的靶向方法，对 13 名志愿者在 10 天洗脱期后饮用一杯含咖啡因的咖啡冲泡液的咖啡干预研究中的血浆样本进行了分析。发现来源于绿原酸的代谢物可分为两组，表现出不同的药代动力学特性。第一组包括阿魏酸和阿魏酸硫酸盐，在血浆中出现较早（约 1 小时）。第二组包含由肠道微生物群形成的特别绿原酸代谢物，出现较晚并在血浆中持续存在（>6 小时）。葫芦巴碱出现较早，但半衰期计算约为 5 小时，持续存在。咖啡因代谢物的血浆水平在咖啡摄入后 2-4 小时显著且逐渐增加，在研究时间范围内未达到 c max。药代动力学特征表明，由于在习惯性饮用几杯咖啡的过程中，特别是葫芦巴碱、咖啡因及其代谢物，以及由肠道微生物群从绿原酸形成的后出现的二氢阿魏酸、阿魏酰甘氨酸和二氢阿魏酸硫酸盐，由于其半衰期较长，在血浆中积累。由于一些这些代谢物已被报道在体内具有抗氧化作用、抗氧化反应元件激活潜力和神经保护特性，因此，一些关键代谢物可能是习惯性终生摄入咖啡所报告的降低炎症和 DM2/AD 风险的原因。
