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Bioappearance and pharmacokinetics of bioactives upon coffee consumption

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Abstract

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.

Identification of coffee key metabolites in human urine using untargeted MS-based profiling and subsequent targeted analyses in plasma using stable isotope dilution assays

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Acknowledgments

We thank Mr. Erkan Firat Yagar for roasting the study coffee, Ms. Maren Ilse, Dr. Oliver Frank, and Mr. Benedikt Kohles for skillful acquisition of the NMR data, Ms. Jennifer Gatzemeier for technical assistance, and Ms. Stefanie Meyer for assistance in mass spectrometry. We thank all volunteers participating in the study. We appreciate valuable discussions with Dr. Benedikt Cramer (Westfälische Wilhelm Universität Münster). The pictures used in Fig. 1 were purchased from http://de.123rf.com. The pictures were photographed/generated by Andy Heyward (pile of raw coffee beans), Keisuke Kai (roasted coffee beans), and Mike Kiev (internal human organs woman).

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Authors and Affiliations

  1. Chair of Food Chemistry and Molecular Sensory Science, Technische Universität München, Lise-Meitner-Str 34, 85354, Freising, Germany

    Roman Lang, Natalie Dieminger, Anja Beusch, Andreas Dunkel, Barbara Suess, Anika Wahl & Thomas Hofmann

  2. Research Center for Nutrition and Food Sciences (ZIEL), Clinical Nutritional Medicine, Technische Universität München, Gregor-Mendel-Strasse 2, 85350, Freising, Germany

    Yu-Mi Lee, Thomas Skurk & Hans Hauner

  3. Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675, München, Germany

    Thomas Skurk & Hans Hauner

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  1. Roman Lang
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Correspondence to Thomas Hofmann.

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Lang, R., Dieminger, N., Beusch, A. et al. Bioappearance and pharmacokinetics of bioactives upon coffee consumption. Anal Bioanal Chem 405, 8487–8503 (2013). https://doi.org/10.1007/s00216-013-7288-0

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  • DOI: https://doi.org/10.1007/s00216-013-7288-0

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