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(The FASEB Journal. 1999;13:977-994.)
© 1999 FASEB

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

JOANNE M. UPSTON, ANDREW C. TERENTIS and ROLAND STOCKER1

Biochemistry Group, The Heart Research Institute, Sydney, Australia

1Correspondence: Biochemistry Group, The Heart Research Institute, 145 Missenden Rd., Camperdown, Sydney, NSW 2050 Australia. E-mail: r.stocker{at}hri.org.au

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 {alpha}-tocopherol ({alpha}-TOH, vitamin E), the major lipid-soluble lipoprotein antioxidant, have been studied in detail. Based on the known antioxidant action of {alpha}-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 {alpha}-TOH in lipoprotein oxidation; that is, {alpha}-TOH displays neutral, anti-, or, indeed, pro-oxidant activity under various conditions. This review describes the latter, novel action of {alpha}-TOH, termed tocopherol-mediated peroxidation, and discusses the benefits of vitamin E supplementation alone or together with other antioxidants that work in concert with {alpha}-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.


Key Words: atherosclerosis • lipid peroxidation • antioxidants • LDL




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