Hypercholesterolemia in rats produced by an increase in the ratio of zinc to copper ingested

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Abstract
The experiments were designed to test the hypothesis that an alteration of the amount of metallic elements ingested by rats would produce a change in the concentration of cholesterol in the plasma of the animals. Rats were fed ad libitum a purified diet based upon sucrose, egg white protein, and corn oil, and containing no cholesterol or cholic acid; intakes of zinc and copper were varied by varying the ratios of salts of these elements in the drinking water. Drinking solutions were made with analytical grade reagents dissolved in water distilled from glass vessels. The hypothesis was tested successfully as over a period of 3 years, in two different environments, drinking water with a ratio of zinc to copper of 40 consistently and significantly produced higher concentrations of cholesterol in plasma than did water with a ratio of 5. Explanations of the etiology of coronary or ischemic heart disease other than that relating risk to the quality and quantity of dietary fat consumed have not achieved wide acceptance. Data are cited supporting the hypothesis that increased consumption of sugar, decreased consumption of vegetable fiber, consumption of soft water, and lack of exercise result in an increase of the ratio of zinc to copper available for absorption from the intestinal tract, an increase in the ratio of zinc to copper retained in the body following absorption, or an alteration in the distribution of these elements in certain important organs. This increased ratio of zinc to copper then causes an increased concentration of cholesterol in plasma, and presumably, results in increased risk of coronary heart disease. Such increased risk may add to genetic, dietary, and other factors that influence the atherogenic process(es).

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