Anti-oxidants - a protective role in cardiovascular disease?

Established risk factors for cardiovascular disease (CVD), such as hypertension, smoking and diabetes mellitus, explain only some of the observed variation in clinical events. This has maintained interest in other nutritional and biochemical factors that might contribute to the underlying pathophysiology of CVD. All of these risk factors are associated with increased oxidative stress in the vessel wall, which may contribute to CVD by several mechanisms. Studies in animal models of CVD have suggested that natural and synthetic anti-oxidants can prevent the development of clinical end points. These observations have generated the hypothesis that anti-oxidant therapy might also prevent CVD in human populations. This has been supported by epidemiological studies showing a negative correlation between circulating concentrations or dietary intake of natural anti-oxidant vitamins and CVD event rate. Many studies have also demonstrated a beneficial effect of anti-oxidants on surrogate markers of CVD such as endothelial function and lipoprotein oxidation. However, the results of large prospective randomised controlled intervention trials, mostly involving vitamin E in patients at increased risk of CVD, have been disappointing and have failed to demonstrate the anticipated benefits. This paper will critically examine the evidence and try to offer some explanation for the apparent failure of animal and epidemiological data to translate into meaningful clinical benefits.