Considerations in the development of biomarkers of copper status.

Copper (Cu) is an essential nutrient, but a harmful metal in excess. As part of the North American Dietary Reference Intakes, the Recommended Dietary Allowance for Cu was set using a combination of biomarkers of Cu deficiency, including plasma Cu and ceruloplasmin concentrations, erythrocyte Cu/Zn superoxide dismutase activity, and platelet Cu concentration. Liver damage was the sole indicator used in setting the Tolerable Upper Intake Level. Some studies suggest that these conventional biomarkers may not be sensitive enough to detect marginal reductions or excesses of Cu that could pose a health risk. The insensitivity of conventional biomarkers casts uncertainty as to the prevalence of Cu deficiency or overload in the population and in the accuracy of current nutritional reference values for Cu. Numerous biochemical changes have been associated with alterations in Cu status, and many potential biomarkers of Cu nutriture have been proposed; yet, conventional biomarkers are still the most frequently used, underscoring the need for research efforts to substantiate the use of novel biomarkers. In this report, biomarkers of Cu status are reviewed and practical considerations in the development of novel biomarkers are discussed as diagnostic tools for assessing Cu status in humans.