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United States Department of Agriculture

Agricultural Research Service

Title: Interaction Between Zinc and Iron in Rats: Experimental Results and Mathematical Analysis of Blood Parameters

item Uthus, Eric
item Zaslavsky, Boris

Submitted to: Biological Trace Element Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: December 28, 2000
Publication Date: June 1, 2001
Citation: Uthus, E.O., Zaslavsky, B.G. 2001. Interaction between zinc and iron in rats: Experimental results and mathematical analysis of blood parameters. Biological Trace Element Research. 82(1-3):167-183.

Interpretive Summary: The importance of interactive effects, in general, on nutrient requirements is increasingly recognized. For example, increasing the dietary intake of one nutrient may result in an altered (increase or decrease) requirement of another nutrient. Future recommendations should take into consideration the interactions among nutrients. Interactions between iron and copper and between zinc and copper are known to exist and have been extensively studied. However, the interaction between iron and zinc has not been as widely investigated. This paper looks at traditional as well as novel ways to study interactions - specifically the interaction between iron and zinc. The novel approaches revealed a far broader range of interactions between dietary iron and zinc than was found when traditional methods were used. As a result of our experiment, we conclude that the interaction between iron and zinc is nutritionally important and that the interaction can be harmful or beneficial in nature, depending on the relative concentrations of each element in the diet.

Technical Abstract: The metabolic interrelationships between dietary Fe and Zn have been known for years, but some subtle relationships may have gone unrecognized for two main reasons. Most of the research examining this interaction has used non-nutritional amounts of Zn to study the effects on Fe or large amounts of Fe to study the effects on Zn. Also, because nutrient interactions are not necessarily linear in nature, it may be inadequate to apply linear statistical models to study the interaction between Zn and Fe. In this study we used traditional as well as several nonlinear approaches in analyzing experimental results from groups of rats over a wide range of dietary Zn and Fe. Male weanling Sprague-Dawley rats were used in a 5 x 4 factorially arranged experiment. Dietary variables were Fe (as ferric citrate) at 4, 12, 24, 48, or 96 ug Fe/g diet and Zn (as Zn carbonate) at 5, 10, 20 or 40 ug Zn/g diet. After 7 weeks tissues were collected and weighed, hematological parameters were measured and plasma ceruloplasmin and cholesterol were determined. In addition to interactive effects as shown by analysis of variance, application of other advanced mathematical tools such as log-linear analysis and nonlinear interpolation of experimental data revealed a far broader range of interactions between dietary Fe and Zn. We also found that nonlinear interpolation models such as saturation curves or fractional polynomials suitably fit some of the experimental data and revealed previously unreported relationships between Fe and Zn. As a result of our experiment and its quantitative analysis, we conclude that the interaction between Fe and Zn is nutritionally important and that the interaction can be antagonistic or synergistic in nature. The complete data set can be found at

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