Effects of Antioxidant and Lipid Lowering Treatment on Risk Factors for Cardiovascular Disease : With special reference to Mixed Tocopherols and Stable Fish Oil

Abstract: Vitamin E in food, polyunsaturated fatty acids (PUFAs) and lipid lowering treatment with statins have been found to decrease the risk for cardiovascular disease (CVD) and cardiac death. However, clinical trials revealed no beneficial effect of intake of alpha-tocopherol alone. Absence of tocopherols other than alpha-tocopherol in the clinical studies may account for the conflicting results. The aim of the present investigation was to study the effects and potential mechanisms of mixed tocopherols and lipid lowering treatment with stable fish oil and/or simvastatin on risk factors for cardiovascular disease and potential mechanisms behind the effects.Mixed tocopherols were found to have more potent effects on inhibition of lipid peroxidation and prevention of loss of PUFAs in erythrocytes, than alpha-tocopherol alone. Mixed tocopherols but not alpha-tocopherol prevented ADP-induced platelet aggregation. Effects of mixed tocopherols were associated with increased NO release, ecNOS activation and increased SOD protein levels in platelets. Supplementation with tocopherols increased ecNOS activation, and SOD protein level, and decreased PKC activation in platelets and leukocytes. Mixed tocopherols were more potent than alpha-tocopherol alone in modulating NO release and increasing ecNOS activation.Supplementation with stable fish oil reduced triglycerides (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL) and increased high density lipoprotein cholesterol (HDL), and simvastatin reduced TC, LDL and the LDL/HDL ratio in subjects with hyperlipidemia. The combination of stable fish oil and simvastatin further reduced TC, LDL, the LDL/HDL ratio and TG, showing that simvastatin therapy with addition of stable fish oil may be more beneficial in lowering plasma lipoproteins than simvastatin or fish oil alone. A small daily intake of stable fish oil in bread increased n-3 PUFAs and HDL, and decreased TG and malondialdehyde in plasma in subjects with hyperlipidemia.