Vitamin E and drug metabolism.

Tocopherols and tocotrienols are metabolized by side chain degradation initiated by cytochrome P450 (CYP)-catalyzed omega-hydroxylation followed by beta-oxidation. Whereas alpha-tocopherol is only poorly metabolized, high amounts of the final products, carboxyethyl hydroxychroman (CEHC), are found from other tocols in HepG2 cells and in human urine. CYP3A4 and CYP4F2 were suggested to be involved in tocopherol degradation. CYP3A4 metabolizes most of the drugs and is induced by many of its substrates via the activation of the pregnane X receptor (PXR). Also tocopherols and in particular tocotrienols induce the expression of a PXR-driven reporter gene and the expression of endogenous CYP3A4 and CYP3A5 which is supported by sporadic publications spread over the last 30 years. The potential interference of vitamin E with drug metabolism is discussed in the light of related complications evoked by herbal remedies.