Potential Antiatherogenic Mechanisms of Ascorbate (Vitamin C) and α-Tocopherol (Vitamin E)

Abstract

—The premise that oxidative stress, among several other factors, plays an important role in atherogenesis implies that the development and progression of atherosclerosis can be inhibited by antioxidants. In this minireview we discuss several mechanisms by which the antioxidants ascorbate (vitamin C) and α-tocopherol (vitamin E) may protect against atherosclerosis. These mechanisms include inhibition of LDL oxidation and inhibition of leukocyte adhesion to the endothelium and vascular endothelial dysfunction. Overall, ascorbate appears to be more effective than α-tocopherol in mitigating these pathophysiological processes, most likely as a result of its abilities to effectively scavenge a wide range of reactive oxygen and nitrogen species and to regenerate α-tocopherol, and possibly tetrahydrobiopterin, from its radical species. In contrast, α-tocopherol can act either as an antioxidant or a pro-oxidant to inhibit or facilitate, respectively, lipid peroxidation in LDL. However, this pro-oxidant activity of α-tocopherol is prevented by ascorbate acting as a coantioxidant. Therefore, an optimum vitamin C intake or body status may help protect against atherosclerosis and its clinical sequelae, whereas vitamin E may only be effective in combination with vitamin C.

Vitamins C and E downregulate vascular VEGF and VEGFR-2 expression in apolipoprotein-E-deficient mice

“…Since VEGF seems to be necessary in the development of atherosclerosis [26] and treatment with angiogenesis inhibitors reduces both plaque growth and intimal neovascularization in apoE−/− mice [10], the observed downregulation of VEGF and VEGFR-2 expression by the combination of vitamins C and E would be an additional mechanism by which these agents could prevent and limit atherosclerotic plaque progression [18,30]. Further studies should be conducted in a well-defined human hypercholesterolemic population to assess whether the effects of vitamins C and E supplementation observed in mice can be reproduced also in humans.…”

“…To date, there is no clear evidence from clinical trials that antioxidants provided by dietary intake or in the form of vitamin supplements can reduce the risk of atherosclerosis [16,17]. However, a number of studies in different animal models have considered the potential for different dietary antioxidants to help prevent development and progression of atherosclerosis, and most of the experimental evidence helps substantiate this hypothesis [18,19]. Particularly, ␣-tocopherol has been shown to decrease lipid peroxidation and atherosclerosis in apoE−/− [11].…”

Mechanisms of H2O2-induced oxidative stress in endothelial cells

“…Vitamin E is lipid soluble, scavenges ROS directly, and may have a role in protecting against LDL oxidation (Fontana et al 1999;Carr et al 2000c;Shimazu et al 2001). …”

Estimation of organic matter digestibility, metabolizable energy, phenolic compounds and antioxidant activity of stems and seeds of the <i>Juncus acutus</i> plant in ruminant nutrition

“…Because of increased concern about synthetic antioxidants that can be toxic to animal DNA, there is great interest in finding new and safe antioxidants from natural sources (Muraina, 2009). Plant phenolics include phenolics acids, flavonoids, tannins and the less common stilbenes and lignans, which are known to have antiviral, anti-inflammatory, anti-allergic and anti-carcinogenic properties (Carr et al, 2000;Dai et al, 2010). Phenolics in plants can vary from simple phenolic acids to highly polymerized substances such as tannins.…”