Dietary chitosan inhibits hypercholesterolaemia and atherogenesis in the apolipoprotein E-deficient mouse model of atherosclerosis.
Chitosan, the deacetylated form of chitin, is extracted from the shells of crustaceans. The strong positive charge carried by the chitosan molecule causes it to bind negatively charged substrates such as lipids. Orally administered chitosan binds fat in the intestine, blocking absorption, and has been shown to lower blood cholesterol in animals and humans. As a result it has been proposed that dietary supplementation with chitosan may inhibit the formation of atherosclerotic plaque. We have tested this hypothesis using the apolipoprotein E-deficient mouse model of atherosclerosis. This hypercholesterolaemic animal develops atherosclerosis without the need for dietary or surgical intervention. The apolipoprotein E-deficient mouse therefore provides an ideal model in which to study the effects of dietary chitosan on both blood cholesterol and atherosclerosis. Animals were fed for 20 weeks on a diet containing 5% chitosan or on a control diet. Blood cholesterol levels were significantly lower in the chitosan fed animals throughout the study, and at 20 weeks were 64% of control levels. When the area of aortic plaque in the two groups was compared a highly significant inhibition of atherogenesis, in both the whole aorta and the aortic arch, was observed in the chitosan fed animals--42 and 50%, respectively. Body growth was significantly greater in the chitosan fed animals. This study is the first to show a direct correlation between lowering of serum cholesterol with chitosan and inhibition of atherogenesis, and suggests that the agent could be used to inhibit the development of atherosclerosis in individuals with hypercholesterolaemia.
Ormrod
D J
DJ
Department of Medicine, University of Auckland, New Zealand. d.ormrod@auckland.ac.nz
Holmes
C C
CC
Miller
T E
TE
D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D001161:Arteriosclerosis / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D001835:Body Weight / Q000187:drug effects; D002686:Chitin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D048271:Chitosan; D004032:Diet; D004195:Disease Models, Animal; D006937:Hypercholesterolemia / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D051379:Mice; D018345:Mice, Knockout
D000924:Anticholesteremic Agents; D001057:Apolipoproteins E; D002686:Chitin; D048271:Chitosan