Adding cholesterol to diets of animals induces copper deficiency and promotes oxidative damage

In their recent study examining the effects of dietary lipid overload on bile acid metabolism and gallbladder motility, Kakimoto et al1 fed healthy, castrated male Beagles a high-fat–high-cholesterol (8%) diet and a low-fat diet and found that the high-fat–high-cholesterol diet significantly increased plasma cholesterol concentration, decreased the concentration of taurocholic acid and increased the concentration of taurochenodeoxycholic in bile, and decreased gallbladder contractility. The authors noted that a limitation of their study was that they could not rule out the possibility that the changes in bile acid composition and gallbladder motility were induced by dietary factors other than high amounts of cholesterol and triglyceride.

Importantly, feeding a diet high in cholesterol can induce copper deficiency in animals,2 and copper deficiency can result in hypercholesterolemia.3 Imai et al4 examined aortic cells of rabbits exposed to various types of cholesterol and found that purified cholesterol was less injurious than newly purchased cholesterol, which was less harmful than 5-year-old cholesterol. Vine et al5 fed rabbits a standard diet supplemented with 1% purified cholesterol or 1% oxidized cholesterol (containing 6% oxysterols), and found that rabbits fed oxysterols had a lower plasma cholesterol concentration than did those fed purified cholesterol but had a 64% increase in aortic cholesterol concentration.

It seems likely that the cholesterol used in most of the thousands of similar experiments over the past century had been stored at room temperature for indefinite periods. Researchers who feed cholesterol to animals should add an additional experimental group fed supplemental copper and should use purified cholesterol unless they are studying oxysterols. Copper deficiency may be an important nutrient imbalance, and incorporating an additional experimental group may help distinguish cholesterol effects from copper deficiency effects.

Leslie M. Klevay, MD, SD

School of Medicine and Health Sciences University of North Dakota Grand Forks, ND

  • 1. Kakimoto T, Kanemoto H, Fukushima K, et al. Effect of a high-fat-high-cholesterol diet on gallbladder bile acid composition and gallbladder motility in dogs. Am J Vet Res 2017;78:1406–1413.

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  • 2. Klevay LM. Metabolic interactions among dietary cholesterol, copper, and fructose. Am J Physiol Endocrinol Metab 2010;298:E138–E139.

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  • 3. Klevay LM. Hypercholesterolemia in rats produced by an increase in the ratio of zinc to copper ingested. Am J Clin Nutr 1973;26:1060–1068.

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  • 4. Imai H, Werthessen NT, Taylor CB, et al. Angiotoxicity and arteriosclerosis due to contaminants of USP-grade cholesterol. Arch Pathol Lab Med 1976;100:565–572.

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  • 5. Vine DF, Mamo CL, Beilin LJ, et al. Dietary oxysterols are incorporated in plasma triglyceride-rich lipoproteins, increase their susceptibility to oxidation and increase aortic cholesterol concentration of rabbits. J Lipid Res 1998;39:1995–2004.

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