To begin addressing these pharmacokinetic challenges, we look at a subtle but critically important aspect of the pharmacokinetic profile of polyphenols such as flavonoids as ascertained from the literature. ) posed the problem of the "flavonoid paradox". The paradox is summarized by the observation that several flavonoid polyphenols have been shown to demonstrate therapeutic effects for various pathologies in vivo, and yet their pharmacological profiles suggest poor bioavailability with rapid plasma clearance.