Antioxidant therapy and atherosclerosis: animal and human studies

Oxidation of LDL cholesterol appears to play a central role in the pathogenesis of atherosclerosis. Animal models of atherosclerosis have elucidated this process and have demonstrated an antioxidant effect of vitamin administration that has been correlated with delayed progression or regression of atherosclerosis. However, clinical trials of antioxidants present a confused picture. Explanations proposed for the discrepancy in results include differences in patient characteristics, the antioxidant content of their diets and dose selection. However, a striking feature of these trials is the absence of a biochemical basis for patient inclusion or dose selection. Reliable, quantitative indices of free radical induced modification of lipids, such as F2-isoprostanes have emerged. Future trials of anti-oxidant therapy in cardiovascular disease should be targeted toward patients with high levels of oxidant stress or patients with depletion of endogenous antioxidants. The dose of anti-oxidant should be chosen based on a surrogate readout, such as F2 isoprostanes, that is a reliable, reproducible and easily obtainable in vivo measure of oxidant stress.