A Human Study on the Intra- and Interindividual Variation in Absorption and Metabolism of Coffee Chlorogenic Acids and Effects on Biomarkers of Health in Humans

Coffee is a rich source of caffeoylquinic acids, esters of caffeic or ferulic acid and quinic acid and its consumption is associated with various health benefits. However, upon ingestion of coffee, caffeoylquinic acids are abundantly absorbed, widely metabolised and extensively excreted in humans.
The first part of this thesis addresses the synthesis and subsequent analysis of several glycine conjugates of hydroxycinnamic acid in urine collected by six participants of a pilot human study. For the first time vanilloylglycine has been quantified in urine for the first time after coffee consumption in similar amounts to feruloylglycine, whereas 3,4-dimethoxycinnamoylglycine, 3,4-dimethoxydihydrocinnamoylglycine, 3,4-dimethoxybenzoylglycine and dihydroferuloylglycine have only been detected in trace amounts.
The second part of this thesis describes the chemical synthesis of several hundred milligrams of dihydrocaffeic acid-3-O-sulfate, ferulic acid-4-O-sulfate, and dihydroferulic acid-4-O-sulfate, the development of a rapid LC-MS method for the analysis of the five most excreted urinary metabolites of caffeoylquinic acids, the design and performance of a human study investigating the intra- and interindividual absorption of caffeoylquinic acids in humans and linking these results to biomarkers of health and food intake.
Among 62 participants, an 8-fold variation in excretion of the total amount of the five most abundant, urinary metabolites excreted over 36 hours after coffee consumption was calculated and the intraindividual variation between repeated visits was the highest for colonic metabolites. A moderate, negative correlation of the absorption of caffeoylquinic acids with the weekly consumption of coffee was established. The data suggests a strong impact of colonic catabolism on the absorption and metabolism of caffeoylquinic acids and a reducing effect of heavy coffee consumption on the absorption of caffeoylquinic acids in humans.