Bioappearance and pharmacokinetics of bioactives upon coffee consumption

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.

Role of the small intestine, colon and microbiota in determining the metabolic fate of polyphenols

“…Such data for tissues are conspicuous by their absence but plasma C max values for metabolites absorbed in the proximal gastrointestinal tract rarely exceed a transient 50 nM for a single bolus dose (unless supplemented) [25,[167][168][169] although 3 ,4 -dimethoxycinnamic acid (ca 0.6 µM after ca two cups of coffee) [170] and 4-hydroxybenzoic acid (2.5 µM after 300 g fresh strawberries) [22] are notable exceptions. In contrast, as discussed above, for those catabolites derived from multiple substrates, and especially those associated with commodities consumed repeatedly at short intervals during the day, a higher C max is to be expected, in some cases exceeding 1 µM.…”

Comparing metabolite profiles of habitual diet in serum and urine

“…We found that caffeinated coffee was associated with serum catechol sulfate, but not urinary catechol sulfate. Catechol, a derivative of coffee processing, is conjugated to catechol sulfate to facilitate absorption (65,66). Conjugated polyphenol metabolites generally are eliminated in feces (61).…”

The colonic metabolites dihydrocaffeic acid and dihydroferulic acid are more effective inhibitors of in vitro platelet activation than their phenolic precursors

“…57 On the contrary, concentrations of at least 100 µM were necessary to inhibit the expression of TRAP-and ADPinduced P-selectin by the early metabolites CA and FA, and 5-CQA, respectively, 42,58 while the 12 results of this study showed a significant decrease of ADP-induced P-selectin expression at noticeably lower concentrations (20, 10 and 1 µM for CA, FA and 5-CQA, respectively), indicating that the colonic metabolites may have an even stronger effect on platelet function than their phenolic precursors. Early metabolites from CGA appear at 1 -2 h after coffee intake, and have a short life time of approximately 30 min, 21,59 whereas DHCA and DHFA appear in the circulation 5 -10 h after consumption and their life time is between 0.7 and 2.1 h. 19 A longer circulation time of colonic metabolites, together their higher effect on platelet function, suggest that these colonic metabolites may be the main contributors to the beneficial effect of CGA-rich foods on human platelet function. The differences in efficacy could relate to their molecular structure.…”