Hypercholesterolemia attributable to increased plasma concentrations of low 
density lipoproteins is a well recognized risk factor for the premature 
development of coronary atherosclerosis in both experimental animals and humans. 
Recent studies have indicated that modifications to low density lipoprotein 
result in enhanced uptake of the modified lipoproteins by macrophages and lead 
to accelerated rates of lipid deposition and the creation of foam cells. 
Oxidation of low density lipoprotein has been shown to be one of the 
modifications which leads to uptake of this lipoprotein by scavenger receptors 
present on macrophages and results in intracellular lipid accumulation. 
Treatment of hypercholesterolemic animals with antioxidant drugs, including 
probucol, has been shown to reduce the development of atherosclerosis and 
xanthoma regression has been observed in patients with severe 
hypercholesterolemia treated with this drug. Epidemiologic studies support the 
view that low plasma concentrations of antioxidant vitamins, including vitamin E 
are associated with higher rates of coronary atherosclerosis in humans and that 
supplementation with vitamin E is associated with a decreased incidence of 
coronary artery disease. Prospective clinical trials to assess the potential 
benefit of antioxidant supplementation in high risk patients are currently in 
progress and these trials, when completed, should provide definitive information 
concerning the potential benefits to be derived from supplementation with 
antioxidant vitamins as an adjunctive therapy to prevent the premature 
development of atherosclerosis.