Policosanol in Human Health

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E. Policosanol in Human Health

Much research has been done on the potential of policosanols in lowering blood cholesterol and reducing the development of atherosclerotic plaques Rodriguez et al. 1997; Arruzazabala et al. 2002. Studies have involved a wide range of subjects including experimental animals, healthy volunteers, and elderly patients with hypercholesterolemia. Several studies also have reported cardiovascular benefits of policosanols and its major component octacosanol, without major adverse effects. Policosanols may decrease the risk of atheroma formation by reducing lipid levels, platelet aggregation, endothelial damage, and the development of foam cells. Octacosanol may decrease cholesterol synthesis in the liver before the generation of mevalonate. Octacosanol may down regulate the cellular expression of 3-hydroxy-3-methylglutaryl coenzyme A HMG-CoA reductase. Treatment with octacosanoic acid isolated and purified from sugarcane wax suppressed HMG-CoA reductase production in cultured fibroblasts, and this finding suggests a possible depression of de novo synthesis of the enzyme and cholesterol Menendez et al. 2001. Furthermore, Singh et al. 2006 described that policosanol inhibits cholesterol synthesis in hepatoma cells by activation of AMP-kinase and is well established to suppress HMG-CoA reductase activity. Research indicates that octacosanol at a dose of 5 mgday may reduce LDL and total cholesterol in patients with borderline to mildly elevated serum triacylglycerol levels Castano et al. 2003 and in normocholesterolemic and casein-induced hypercholesterolemic rabbits. 15 Combination treatment policosanol 10 mgday and omega-3 fatty acid 1 gday has been associated with significant inhibition of platelet aggregation in rabbits compared with either drug alone Castano et al. 2006. Absorption and metabolism of nonesterified policosanol have been studied by many researchers. Hargrove et al. 2003 mentioned that the liver may be converting octacosanol to long chain fatty acids, which were subsequently taken up by muscle. The study identified that the administered octacosanol was found in sterols and triacylglycerol, which indicated conversion to fatty acids and esterification. Policosanol metabolism is linked to fatty acid metabolism via β-oxidation. Menendez et al. 2005 demonstrated that octacosanoic acid was formed after incubation of fibroblast cultures with 3H-octacosanol and after oral dosing with policosanol to rats. In addition, shortened saturated myristic, palmitic and stearic and unsaturated oleic, palmitoleic fatty acid were also formed after oral dosing with policosanol to monkeys. More rapid onset of effects suggests that oxidation of policosanols to very long-chain fatty acids may be necessary for their hypocholesterolemic actions and enhance the breakdown of LDL particles McCarty 2005. In another study, dietary octacosanol was thought to increase lipid catabolism to generate more energy for improvement of motor endurance; and this action may contribute in reductions of plasma triglyceride levels. Octacosanol is already recognized as an ergogenic product used to enhance athletic performance Taylor et al. 2003. 16 In an effort to identify the potential mechanism for the antiatherogenic effects of policosanols, Ng et al. 2005 investigated the effects of these natural compounds on LDL oxidation and bile acid excretion. Policosanols showed no antioxidant activity in human LDL particles but increased bile acid secretion in hamsters. However, other research groups using policosanol from alternative sources have failed to reproduce the efficacy of these alcohols observed in earlier studies. Lin et al. 2004 reported that wheat germ policosanol 20 mgday had no beneficial effects on blood lipid profiles in subjects with normal to mildly elevated cholesterol concentrations. Kassis et al. 2007 mentioned that sugarcane policosanol treatment at a dose of 275 mgkg diet had any significant cholesterol-lowering effect on plasma lipid levels in Golden Syrian hamsters. III. MATERIALS AND METHODS

A. Materials