Table 5.

Plausible mechanism of plant polyphenols toxicity.

Mechanism	Predisposing Factors	Example	Reference
Pro-oxidant activity	High polyphenol concentration, presence of iron and H2O2, and a high pH, auto-oxidation-induced generation of ROS	Epigallocatechin gallate	[169,170,171]
Genotoxicity	High concentration and long-term consumption of high doses	Caffeic acid	[172]
Interaction with pharmaceuticals	Changes in bioavailability and pharmacokinetics of benzodiazepines by inhibition of cytochrome P450 3A4 (CYP3A4)	Naringenin (grapefruit juice)	[173]
Antinutritional effect: inhibition of iron absorption	Long-term consumption of large amounts of tea and coffee	Tannins	[174,175,176]
Interaction with the endocrine system	Large consumption of isoflavones with estrogenic activity	Genistein, daidzein, and glycitein	[177,178]