Does pharmacodynamic interaction of nonenzymatic antioxidants modify response to antioxidant therapy in the process of atherosclerosis?

A discrepancy exists between clinical trials and epidemiological studies on the effect of antioxidants on cardiovascular disease. This discrepancy could be attributed to the lack of knowledge on the effect of interaction of exogenous antioxidant supplementation with one another or on the effect of interaction of exogenously administered antioxidant vitamins with endogenous ones. This study attempts a systematic review of available data on possible synergistic, additive, or antagonistic action of nonenzymatic antioxidants in atherosclerosis. Electronic databases were searched with the available search terms up to and including February 2010. Eligibility criteria were full publications, clinical trials, epidemiological studies, or in vitro or in vivo studies that investigated the effect of pharmacodynamic interaction of 2 or more antioxidants in the process of atherosclerosis and /or the mechanism of interaction. Eligible clinical trials should have at least 4 arms, 1 arm for the study of each antioxidant alone, 1 for the effect of both antioxidants, and 1 arm for the effect of placebo. In vitro data as well as the limited number of identified randomized clinical trials suggested that coadministration of antioxidants results in synergistic or additive interaction in the process of atherosclerosis. No study demonstrated antagonistic interaction between antioxidants.