Skip to main content
ARS Home » Plains Area » Grand Forks, North Dakota » Grand Forks Human Nutrition Research Center » Dietary Prevention of Obesity-related Disease Research » Research » Publications at this Location » Publication #91078


item Reeves, Phillip

Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/18/1998
Publication Date: N/A
Citation: N/A

Interpretive Summary: It is well known that humans or animals who eat foods that contain a lot of zinc, or take vitamin pills that are high in zinc for a long time, will develop a mild to severe copper deficiency. The current theory says that eating a lot of zinc, for example, 4 times the RDA will stimulate the production of a small protein in the intestinal lining. This protein will then bind copper and prevent its absorption into the body. This protein is called metallothionein, or MT for short. By genetic engineering, other researchers have produced a mouse that cannot make MT. In the present experiment, we used this mouse to test if the above theory was really true. If the mouse cannot make MT, then it should not get copper deficient when fed a high-zinc diet. We fed some of these mice and some control mice (ones that can make MT) diets that contained normal amounts of zinc and some that contained much more zinc. The results showed that, indeed, the mouse without MT got copper deficient when fed the same high- zinc diet the same as the mouse did that had MT. This study strongly suggests that the old theory is not true and that stimulation of MT is not necessary for high-zinc to bring about a copper deficiency. We suggest instead that the high zinc is inhibiting a copper transport protein in the intestinal membrane, and copper cannot be absorbed.

Technical Abstract: Humans and animals develop low copper (Cu) status when fed diets containing large amounts of zinc (Zn) for extended periods. Current theory states that Zn-induced metallothionein (MT) in the intestinal mucosa binds Cu and prevents its absorption. We tested this theory by using a mouse model with a disruption in the MT gene that renders it incapable of producing functional MT-I and MT-II (MT-null). If the theory is true, then the MT-null mouse should not develop low Cu status when fed a high-Zn diet. Groups of 4-week old MT-null and control mice were fed for one week a diet that contained 35 mg Zn and <1 mg Cu/kg. Each genotype was then divided into two groups each. One group was fed a diet containing 35 mg Zn and 1.5 mg Cu/kg and the other was fed a diet containing 400 mg Zn and 1.5 mg Cu/kg. After 14 days, plasma was harvested and plasma ceruloplasmin amine oxidase (CPAO) activity, a good indicator of Cu status, was determined. The plasma CPAO activity of control mice fed 400 mg Zn/kg diet was 50% of that in similar mice fed 35 mg Zn/kg. Likewise, plasma CPAO activity in MT-null mice fed 400 mg Zn/kg diet was 40% of that in MT-null mice fed 35 mg Zn/kg. These data suggest that MT induction is not required for the development of low Cu status in mice fed a high-Zn diet, and we offer the hypothesis that the actual mechanism involves the inhibition of a Cu transporter by Zn.