Analysis of the Bioactivity, Metabolism, and Pharmacokinetics of Anthocyanins in Humans

ANALYSIS OF THE BIOACTIVITY, METABOLISM, AND PHARMACOKINETICS OF ANTHOCYANINS IN HUMANS Colin Kay Advisors: University of Guelph, 2004 Professor B. J. Holub Professor G. Mazza Recent interest in the health-promoting properties of berry anthocyanins has been based on studies reporting their significant in vitro antioxidant activities. However, information regarding the bioavailability, metabolism, and antioxidant activity of anthocyanins in humans is largely unexplored. The overall objective of this thesis research was to examine the antioxidant bioactivity, metabolism, and pharmacokinetics of anthocyanins in humans through a series of three exploratory investigations. The objective of the first investigation was to determine if the consumption of blueberries resulted in the absorption of anthocyanins and if the appearance of anthocyanins corresponded with changes in the antioxidant capacity of the blood. The aim of the second investigation was to identify metabolites of anthocyanins (specifically cyanidin 3glycosides) post-consumption of chokeberries. Lastly, the goal of the third investigation was to establish the pharmacokinetics of parent and metabolized anthocyanins. In the first investigation, the concentration of anthocyanins in human serum positively correlated with an increase in antioxidant capacity of the serum; however, the concentration of parent anthocyanins appeared insufficient to account for the magnitude of antioxidant effect. It was hypothesised that unidentified anthocyanin metabolites likely contributed to the observed antioxidant effect. In the second investigation, anthocyanin metabolites were identified in the serum and urine as glucuronide and methyl derivatives of the parent cyanidin 3-glycosides. The third study evaluated the pharmacokinetic parameters of both parent and metabolized anthocyanins. The total cumulative concentration of anthocyanins (parent and metabolites) detected in the serum over a 7h sampling regime was 172.96 ± 7.44 μg·h/mL with a maximum concentration of 44.86 ± 2.82 μg/mL occurring within 2.8h. Additionally, the total urinary excretion of metabolites and parent compounds over 24h was 1071.54 ± 375.46 μg, reaching a maximal rate of excretion of 202.74 ± 85.06 μg/h at 3.72 ± 0.83h and having an elimination half-life of 4.12 ± 0.4h. Only 33% of the total anthocyanins detected in the serum were identified as the parent cyanidin 3glycosides with 67% occurring as conjugated metabolites. This evidence suggests that anthocyanins are absorbed, metabolized, and readily excreted in humans, and their metabolites likely contribute significantly to their overall antioxidant bioactivity.