Submitted to: Biological Trace Element Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: November 21, 2001
Publication Date: June 1, 2002
Citation: Saari, J.T. 2002. Renal copper as an index of copper status in marginal deficiency. Biological Trace Element Research. 86:237-247. Interpretive Summary: Severe dietary copper deficiency is known to cause widespread effects on bodily functions. Humans rarely suffer from severe copper deficiency, but may still consume less than the optimal amount of copper and thus may be marginally deficient. Therefore, it is important to develop methods for the study of marginal copper deficiency. It is important, for instance, to determine the proper copper status index and the means by which different copper intakes will be compared. In this study we fed rats graded concentrations of dietary copper to determine whether variables known to be affected by severe copper deficiency might also be affected by marginal deficiency. Three copper status indices, liver and kidney copper concentrations and the activity of a circulating copper-dependent enzyme (ceruloplasmin), were compared. By using a method of statistical analysis (linear regression) that takes into account variation between animals, marginally deficient animals exhibited no association between liver copper or ceruloplasmin and any of six cardiovascular variables known to be affected by severe deficiency. Kidney copper showed an association with three of the six variables and is thus revealed to be a superior index of copper status when copper deficiency is not severe. This is important to our understanding of the effect that dietary copper has on the heart and circulation.
Technical Abstract: Marginal copper (Cu) deficiency is difficult to study, in part because its effects may be small, but also because feeding of a deficient diet may not cause a discernable change in Cu status. The key to resolution of effects may be in the choice of Cu status index. In this study, liver Cu concentration, a commonly used index of Cu status, was compared with activity of ceruloplasmin (CP), a circulating Cu-dependent enzyme, and kidney Cu concentration for their utility in resolving effects of marginal Cu deficiency. Seventy male, weanling rats were fed diets containing, nominally, 0, 1.5, 3, 4.5 or 6 mg Cu/g of diet for 5 weeks. All three indices showed strong depression with severe deficiency (dietary Cu=0), but were relatively weak in their ability to distinguish between animals fed marginally deficient diets when compared by group statistics (ANOVA). Further, group statistics revealed no effect of marginal deficiency on six other variables known to change with severe Cu deficiency: heart weight/body weight, hematocrit, red cell distribution width, neutrophil count, glycated hemoglobin and platelet count. To take into account inter- animal variation, the three putative indices were plotted against these six variables and linear regression was performed on points representing marginally-deficient rats. None of the variables showed significant regression with liver Cu or serum ceruloplasmin, but three showed significant regression with kidney Cu. These findings indicate that kidney Cu is preferable to liver Cu or ceruloplasmin as an index of Cu status in marginal deficiency and that linear regression is a possible way of testing for effects of marginal Cu deficiency, especially when effects are subtle.