Plasma LDL cholesterol lowering by plant phytosterols in a hamster model

Cardiovascular disease is still the main cause of death in the US. High plasma cholesterol, 51.9% of Americans have cholesterol levels of 200 mg/dl or higher and especially low-density lipoprotein (LDL) cholesterol, and high ratios of LDL to high-density lipoprotein (HDL) cholesterol are risk factors for cardiovascular disease. Plant stanol esters have been shown to be effective in reducing plasma cholesterol. Other phytosterol-like compounds such as oryzanol, a mixture of ferulate esters from rice bran, and tomatine, a glycoalkaloid in green tomatoes, have also shown cholesterol-reducing properties in test animals. Investigations of mechanisms and uses of plant phytosterols are facilitated by animal models that respond to phytosterols, as well as other known cholesterol-lowering agents. The hypercholesterolemic LDL hamster is used to efficiently screen phytosterols for plasma cholesterol-lowering properties. Hypercholesterolemia is induced in these animals by saturated fat and fish oil, and dietary cholesterol intake similar to that of humans, 0.025–0.05%. This results in rapid LDL hypercholesterolemia. Prolonged feeding of the hypercholesterolemic diet results in aortic fatty streak formation, which can be retarded by the antioxidants alphatocopherol or catechin. Known plasma cholesterol-reducing agents such as cholestyramine, soluble dietary fiber, stanol esters, oryzanol, and tomatine reduce total and LDL cholesterol. Gas chromatography/mass spectrometry indicates that tomatine binds cholesterol, but fiber and cholestyramine increase bile acid excretion. Cardiovascular disease affects about 58 million people, or one-fourth of the US population, and kills about 960,000