Effects of antioxidant status and oral delivery systems on quercetin bioavailability

Quercetin is one of the most abundant dietary flavonols that has putative cardioprotective activities. Quercetin has low bioavailability and elicits highly variable inter-individual responses following its ingestion, however, factors regulating quercetin bioavailability remain unclear. Since bioactivities of quercetin partly depend on its bioavailability, elucidating determinants for quercetin bioavailability will facilitate a better understanding of its cardioprotective activities. Therefore, this dissertation aimed to investigate the influence of endogenous factor (antioxidant status) and exogenous factor (dietary fat and nano-formulation) on quercetin bioavailability. The central hypothesis of this dissertation was that adequate antioxidant status would improve quercetin aglycone bioavailability and that its bioavailability would be enhanced by co-ingestion with dietary fat or administration as nano-emulsion. Our studies in obese adults demonstrated that dietary fat improved quercetin bioavailability by increasing its absorption. In addition, a quercetin aglycone-containing nanoemulsion was developed using self nano-emulsifying drug delivery system. Our studies in rats demonstrated that the designed quercetin nanoemulsion enhanced quercetin absorption, thereby improving its bioavailability, and increasing its intestinal and hepatic accumulation. Lastly, contrary to our hypothesis, studies in healthy adults showed that greater quercetin bioavailability was associated with inadequate plasma vitamin C status and greater plasma endotoxin. Collectively, this dissertation demonstrated that greater quercetin aglycone bioavailability could be achieved when it was ingested with dietary fat or administered orally as nano-emulsion, or when inadequate plasma vitamin C status and greater intestinal permeability were present. The findings described herein are of significance in that they provide the foundational basis for development of effective and feasible strategies to improve quercetin bioavailability in humans. These findings will also facilitate intervention studies aiming to evaluate putative cardioprotective activities of quercetin and development of dietary recommendation for quercetin in effort to mitigate CVD risks.