Lipid peroxidation, antioxidants and cardiovascular disease: how should we move forward?

Time for primary review 27 days. It is widely agreed that increased consumption of fruits, grains and vegetables, decreased intake of saturated fats, a moderate degree of exercise and perhaps judicious consumption of red wine or other alcoholic beverages (or even tea) would improve the cardiovascular health of the populations in most developed and ‘near-developed’ countries [1–8]. Fruits, grains, teas, vegetables and red wines are rich in antioxidants (ascorbate, tocopherols, tocotrienols, flavonoids, other phenols and carotenoids are among the antioxidants found in various plants consumed by humans; reviewed in [9]), and so it is widely thought that antioxidants make an important contribution to this cardiovascular protective effect [9–14]. This assumption is logical, because there is good evidence that oxidative damage contributes to the pathology of atherosclerosis and vascular dysfunction generally, and that free radicals are involved in myocardial ischemia-reperfusion injury [9,15–20]. However, intervention trials with vitamin E that assess clinical end-points are giving a confused picture [21–23]. Indeed, foods and beverages derived from plants are chemically complex, and cardiovascular protective effects could also arise from many other components or mixtures of components present, including fibre, immunostimulatory agents, monounsaturated fatty acids, agents that modulate cholesterol synthesis, B-vitamins, folic acid, agents modulating nitric oxide production, and even the humble ethanol molecule itself [2,3,5,6,14,24–29]. One obvious way to assess the contribution of antioxidants to the cardiovascular protective effects of the above diets is to conduct intervention trials with single antioxidants, or combinations of a few antioxidants. For example the intervention trials with β-carotene convincingly demolished the concept that this carotenoid is an important anti-cancer agent in humans, at least in smokers [30]. Hence high plasma levels of β-carotene are negatively associated with cancer incidence because both are a consequence of eating a good diet; β-carotene is not …