Atherosclerosis and Oxidant Stress: The End of the Road for Antioxidant Vitamin Treatment?

Abstract

Extensive experimental data have revealed a central role for oxidative stress in atherogenesis and suggested a potential role for 'antioxidant' treatment in cardiovascular disease (CVD) [1-11]. Experimental data, however, have not translated into clinical benefit: most antioxidant vitamin trials have failed to reduce cardiovascular morbidity and mortality [12]. Moreover, recent clinical trials have suggested that mono-therapy with certain antioxidant vitamins like vitamin E may, in fact, be detrimental [13]. As a result of the disappointing outcome of 'antioxidant' vitamin trials, some authors have questioned both the utility of 'antioxidant' treatment in CVD and the supposedly central role of oxidative stress in atherogenesis [14-19]. Other investigators, however, sustain that the beneficial effects of lipid lowering and anti-hypertensive treatment are at least, in part, due to their 'antioxidant' properties, in addition to their specific pharmacological properties [20, 21]. Oxidant stress plays a pivotal role in atherogenesis, however, the clinical promise of antioxidant vitamins has failed to translate into clinical benefit. Increasing evidence suggests that more rigorous clinical trial designs are necessary to effectively divulge antioxidant utility and that a multifaceted antioxidant approach to atherosclerosis may yield the most clinical reward. This article reviews currently available evidence on the role of oxidant stress in atherosclerosis, analyzes the results of large anti-oxidant trials, and suggests ways to investigate the true role of antioxidant treatment in the clinical setting.

One Enzyme, Two Functions

“…ROS and reactive nitrogen species are not just harmful but also vital to cell function, and some clinical trials demonstrated even augmented mortality after anti-oxidant treatment (31)(32)(33). Hence, the outcome of anti-oxidant treatment depends on the overall context, the cell type, efficient targeting, and the nature of the radical species and its detoxification product.…”

Total Antioxidant Capacity of Diet and Risk of Stroke

“…Phytochemicals can inhibit oxidative stress and inflammation by scavenging reactive oxygen species and reactive nitrogen species. 3 Because not only fruits and vegetables contribute to dietary antioxidants, it is important to study the overall effect from all antioxidants in the diet. The total antioxidant capacity (TAC) aims to measure the free radical-reducing capacity of all antioxidants in the diet and takes into account synergistic effects between substances.…”

Hypoglycemic and Hypolipidemic Effects of Raisin Aqueous Extract “Karkni” in Alloxan-Induced Diabetic Rats

“…In diabetic rats the elevation observed in uric acid level could be due to the increased abundance and activity of xanthine oxidase. It was responsible for the formation of uric acid and also serves as an important biological source of ROS (superoxide) that contribute to oxidative damage involved in many pathological processes such as diabetes, atherosclerosis, cancer and aging [29][30][31]. Moreover, decreasing levels of HbA1c observed in (D+C2) group can reduce the risk of lipid peroxidation [32].…”