Disposition of Flavonoids for Personal Intake

Flavonoids represent a group of polyphenolic phytochemicals. Diverse biological activities of flavonoids are becoming increasingly popular in scientific and public research. Epidemiological human intervention studies showed association of flavonoids to several diseases, which include cancer, neurodegeneration, and cardiovascular diseases. Variation in pathways affecting absorption, distribution, metabolism, and excretion (ADME) of flavonoids possibly influences exposure at the circulatory system, thus modifying disease risk in individuals. This article focuses on current knowledge on factors affecting disposition of flavonoids and personal intake. These factors include nuclear receptors (NRs), gene transcriptional regulation of drug-metabolizing enzymes (DMEs), and efflux transporters (ETs). First, we summarize the current knowledge for main subclasses of flavonoids and their metabolism pathways. Important novel insights proved that regulatory mechanisms control enzyme activities and gene expressions of these DMEs and ETs by NRs. Typically, considerable evidence showed that NRs directly or indirectly regulate expressions of critical DMEs and drug transporters. Variation in metabolism pathways of flavonoids, polymorphic phase II enzymes, and ETs contributes to variability of flavonoid disposition. Covariation of enzymes, ETs, and NRs can explain individual variability of flavonoid disposition. Thus, identified gaps in these factors must be addressed to further understand flavonoid intake, which can serve as basis for more comprehensive evaluation of the effects of these dietary supplies on health.