Vitamin E, nuclear receptors and xenobiotic metabolism

Arch Biochem Biophys. 2004 Mar 1;423(1):6-11. doi: 10.1016/


Supplemental vitamin E (alpha-tocopherol) is taken daily by more than 35 million people in the US. Following absorption and liver uptake, the fate of vitamin E is largely unknown. Of potential importance are recent clinical studies that have reported adverse effects of vitamin E that may be directly related to its hepatic metabolism. In an in vitro system, both vitamin E and rifampicin, a known stimulator of xenobiotic metabolism, activated the pregnane X receptor (PXR), an orphan nuclear receptor. PXR as a heterodimer with the retinoid X receptor (RXR), binds to specific cis-elements in the promoter regions of genes. PXR/RXR regulates a constellation of genes involved in xenobiotic detoxification, including oxidation, conjugation, and transporters. Importantly, PXR/RXR regulates the cytochrome P450 (CYP), CYP3A, involved in the hepatic detoxification of more than 50% of prescription drugs. Vitamin E acting as a PXR ligand could alter these PXR-mediated reactions. Unfortunately, the extent to which pharmacologic doses of vitamin E modulate these pathways in vivo has not been determined.

Publication types

  • Review

MeSH terms

  • Animals
  • Antioxidants / adverse effects
  • Humans
  • Pregnane X Receptor
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Receptors, Steroid / metabolism
  • Vitamin E / metabolism*
  • Xenobiotics / metabolism*
  • alpha-Tocopherol / adverse effects


  • Antioxidants
  • Pregnane X Receptor
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Steroid
  • Xenobiotics
  • Vitamin E
  • alpha-Tocopherol