Potential Modulation of Phytochemical Bioavailability by Furanocoumarins from Citrus × paradisi

Abstract

The in vivo efficacy of dietary phytochemicals, known for their antioxidant, anti-inflammatory, and neuroprotective properties, is often limited by poor bioavailability due to cytochrome P450 3A4 mediated metabolism. This review explores the potential of furanocoumarins from grapefruit (Citrus × paradisi) to modulate the bioavailability of these compounds by inhibiting CYP3A4. A narrative review of the literature was conducted. The PubMed database was searched up to December 2024 using the keywords "phytochemistry," "grapefruit juice," "furocoumarins," "bioavailability," and "CYP3A4". Inclusion criteria were peer-reviewed English language articles with full-text availability directly addressing phytochemical bioavailability or grapefruit juice effects. The literature indicates that furanocoumarins in grapefruit juice are potent inhibitors of intestinal CYP3A4, significantly affecting the metabolism of various drugs. While extensive research exists on drug-food interactions, studies on the interaction between furanocoumarins and food-derived phytochemicals are limited.  The significant inhibitory effect of grapefruit juice on CYP3A4 suggests a potential for modulating the bioavailability of dietary polyphenols metabolized by this enzyme. Further research is warranted to explore specific polyphenol-CYP3A4 interactions to optimize phytochemical bioavailability for therapeutic benefits, while also considering potential risks in individuals taking CYP3A4-metabolized drugs.