Antioxidant therapy and atherosclerosis: Animal and human studies

Oxidation of LDL cholesterol appears to play a central role in the pathogen esis of atherosclerosis. Animal models of atherosclerosis have elucidated t his process and have demonstrated an antioxidant effect of vitamin administ ration that has been correlated with delayed progression or regression of a therosclerosis. However, clinical trials of antioxidants present a confused picture. Explanations proposed for the discrepancy in results include diff erences in patient characteristics, the antioxidant content of their diets and close selection. However, a striking feature of these trials is the abs ence of a biochemical basis for patient inclusion or dose selection. Reliab le, quantitative indices of free radical induced modification of lipids, su ch as F2 - isoprostanes have emerged. Future trials of anti-oxidant therapy in cardiovascular disease should be targeted toward patients with high lev els of oxidant stress or patients with depletion of endogenous antioxidants . The dose of anti-oxidant should be chosen based on a surrogate readout, s uch as F2 isoprostanes, that is a reliable, reproducible and easily obtaina ble in vivo measure of oxidant stress. (C) 2001, Elsevier Science Inc.