ISMNT NEWS: Disease Prevention by Exploring Molecular Mechanisms Linked to Nutrition ************************************************************************************

ISMNT News #5 deals with vitamin E supplements. Vitamin E supplements: Do we take the wrong (alpha- vs. gamma) form which is a Trojan horse? ...because large doses of dietary alpha-tocopherol displace gamma-tocopherol in plasma and other tissues, the current wisdom of vitamin E supplementation with primarily alpha-tocopherol should be reconsidered ...

The key reference is by:

Christen, S. et al.



Division of Biochemistry and Molecular Biology, University of California, Berkeley 94720


Proc Natl Acad Sci U S A, 1997 Apr 1, 94:7, 3217-22

... Peroxynitrite, a powerful mutagenic oxidant and nitrating species, is formed by the near diffusion-limited reaction of .NO and O2.- during activation of phagocytes. Chronic inflammation induced by phagocytes is a major contributor to cancer and other degenerative diseases. We examined how gamma-tocopherol (gammaT), the principal form of vitamin E in the United States diet, and alpha-tocopherol (alphaT), the major form in supplements, protect against peroxynitrite-induced lipid oxidation. Lipid hydroperoxide formation in liposomes (but not isolated low-density lipoprotein) exposed to peroxynitrite or the .NO and O2.- generator SIN-1(3-morpholinosydnonimine) was inhibited more effectively by gammaT than alphaT. More importantly, nitration of gammaT at the nucleophilic 5-position, which proceeded in both liposomes and human low density lipoprotein at yields of approximately 50% and approximately 75%, respectively, was not affected by the presence of alphaT. These results suggest that despite alphaT's action as an antioxidant gammaT is required to effectively remove the peroxynitrite-derived nitrating species.

We postulate that gammaT acts in vivo as a trap for membrane-soluble electrophilic nitrogen oxides and other electrophilic mutagens, forming stable carbon-centered adducts through the nucleophilic 5-position, which is blocked in alphaT. Because large doses of dietary alphaT displace gammaT in plasma and other tissues, the current wisdom of vitamin E supplementation with primarily alphaT should be reconsidered.