The development of food fortified with polyphenols and polyphenol-rich foods represents a novel approach to prevent or
attenuate type 2 diabetes. It has been reported that type 2 diabetes may affect the pharmacokinetics of various drugs in several animal
models. There is powerful evidence linking dietary polyphenols consumption with the risk factors defining type 2 diabetes, even if some
opposite results occurred. This mini-review summarizes important advances on diabetes-associated changes in pharmacokinetics of
natural polyphenols. The pharmacokinetic behavior between drugs and dietary polyphenols probably may be different due to (i) Ingested
dose/amount per day. The dietary polyphenol intake per day is much higher than that of clinical drugs; (ii) Complexity of the components.
Clinical drugs are well-characterized and typically small molecules. However, the polyphenols in diet are unimaginably complex; (iii)
Interaction with food proteins. Although the effects of food proteins on the bioavailability of polyphenols are still not examined in much
detail, direct binding interactions of polyphenols to proteins always occur; (iv) The most common polyphenols in the human diet have a
low intrinsic activity and are poorly absorbed from the intestine, highly metabolized, or rapidly eliminated. Although there is very limited
information available so far, it is proposed that type 2 diabetes influences the pharmacokinetic behavior of dietary polyphenols including:
i) competition of glucose with polyphenols regarding binding to plasma proteins; ii) weakened non-covalent interaction affinities of
plasma proteins for natural polyphenols due to protein glycation in type II diabetes; iii) the enhanced clearance of polyphenols in type 2
diabetes. An understanding of diabetes-associated changes in absorption, distribution, metabolism, elimination and bioactivities of natural
polyphenols as well as the mechanism of the variability should lead to the improvement of the benefits of these polyphenols and clinical
outcomes for diabetics.