Pharmacokinetics of primary atractyligenin metabolites after coffee consumption

Roasted coffee contains atractyligenin glycosides (ATC Glcs, 2-O-β-D-glucosyl atractyligenin "ATC Glc" and 3′-O-β-D-glucosyl-2′-O-isovaleryl-2-O-β-D-glucosylatractyligenin "ATC Glcglc"), which are not reported in any other food item or non-essential food. Consumption of roasted coffee leads to plasma appearance of metabolites of ATC Glcs. These metabolites (ATC Mets) are formed from ATC Glcs provided by the coffee brew. ATC Mets are detectable in the plasma and are excreted with the urine. Analysis of plasma and urine after coffee consumption and detection of ATC Mets indicates coffee consumption, because ATC Mets are not found in biofluids when no coffee was consumed. Consequently, ATC Mets could serve as dietary biomarkers for coffee consumption.

Intact ATC Glcs in roasted coffee comprise 2-O-β-D-glucosyl atractyligenin (ATC Glc) and 3′-O-β-D-glucosyl-2′-O-isovaleryl-2-O-β-D-glucosylatractyligenin (ATC Glcglc). No traces of these intact ATC Glcs from roasted coffee were detected in plasma or urine before or after coffee consumption (human intervention study, n=12 participants), indicating ATC Glcs were not bioavailable. The analytes atractyligenin ("1"), 2β-hydroxy-15-oxoatractylan-4α-carboxylic acid ("5"), atractyligenin-19-O-β-D-glucuronide ("M1"), 2β-hydroxy-15-oxoatractylan-4α-carboxy-19-O-β-D-glucuronide ("M2"), 2β-hydroxy-15-oxoatractylan-4α-carboxylic acid-2-O-β-D-glucuronide ("M3") were quantified (UHPLC-MS/MS) in urine and plasma after coffee consumption to calculate pharmacokinetic parameters. ~10% of consumed ATC Glcs were excreted as ATC Mets in the urine ("1"~65% and "M1"~35%) within 10h after coffee. Control trial samples contained only traces of ATC Mets, probably from incomplete washout. "1" and "M1" showed two plasma maxima (0.5h, 10h). Cmax was 172.2±68.5 nM (0.5h) and 60.1±35.8 nM (10h) for "1" and 22.1±7.8 nM (0.5h) and 20.5±9.1 nM (10h) for "M1". The metabolites "M2" and "M3" appeared in negligible concentration.

The findings indicate that intact ATC Glcs are not bioavailable. They are cleaved early (0.5h) and late (10h) in the GI tract, leading to the bioavailable aglycone atractyligenin ("1"), which is quickly conjugated to form "M1". The plasma profiles with two maxima suggest cleavage occurs in two different regions (prox. and distal. GI). Cleavage in distal GI could involve microbiota. The low recovery (~10%) of consumed ATC Glcs in the 0-10h urine suggests either fecal excretion, substantial metabolic breakdown and/or substantially longer excretion periods beyond the studied 10 h.