Tocopherol‐mediated peroxidation of lipoproteins: implications for vitamin E as a potential antiatherogenic supplement

The ‘oxidation theory’ of atherosclerosis proposes that oxidation of low density lipoprotein (LDL) contributes to atherogenesis. Although little direct evidence for a causative role of ‘oxidized LDL’ in atherogenesis exists, several studies show that, in vitro , oxidized LDL exhibits potentially proatherogenic activities and lipoproteins isolated from atherosclerotic lesions are oxidized. As a consequence, the molecular mechanisms of LDL oxidation and the actions of α‐tocopherol (α‐TOH, vitamin E), the major lipid‐soluble lipoprotein anti‐oxidant, have been studied in detail. Based on the known antioxidant action of α‐TOH and epidemiological evidence, vitamin E is generally considered to be beneficial in coronary artery disease. However, intervention studies overall show a null effect of vitamin E on atherosclerosis. This confounding outcome can be rationalized by the recently discovered diverse role for α‐TOH in lipoprotein oxidation; that is, α‐TOH displays neutral, anti‐, or, indeed, prooxidant activity under various conditions. This review describes the latter, novel action of α‐TOH, termed tocopherol‐mediated peroxidation, and discusses the benefits of vitamin E supplementation alone or together with other antioxidants that work in concert with α‐TOH in ameliorating lipoprotein lipid peroxidation in the artery wall and, hence, atherosclerosis.—Upston, J. M., Terentis, A. C., Stocker, R. Tocopherol‐mediated peroxidation of lipoproteins: implications for vitamin E as a potential antiatherogenic supplement. FASEB J. 13, 977–994 (1999)