American Journal of Clinical Nutrition, Vol. 88, No. 3, 819S,
September 2008
© 2008 American Society for Nutrition
Molecular Biomarkers of Copper Homeostasis |
Preface
Ricardo Uauy,
Magdalena Araya and
Bo Lönnerdal
This supplement on copper biomarkers is the product of a scientific meeting held in Viña del Mar, Chile, in September 2007. The articles here provide a select update to the 1998 publication in this Journal addressing genetic and environmental determinants of copper metabolism.
The individual articles partially overlap and therefore provide a comprehensive treatise of our current knowledge of copper metabolism, with special emphasis on elevated copper intakes. Beginning with genomics approaches, the reader will be provided insights about the homeostatic regulation of copper metabolism and its potential limitations. On the basis of the best available scientific evidence, we examine key indicators of copper homeostasis that serve as potential biomarkers for deficit and excess. The basis for a good biomarker is its ability to predict a given outcome, in this case, adverse consequences from deficit or excess. In doing so, we examined the basic molecular and cellular underpinnings of copper metabolism as well as the public health relevance of copper exposure. We have learned from bioinformatics the multiple dimensions and interrelations of putative copper proteins that could serve as biomarkers; in response to deficiency, the traditional biomarkers serve well to characterize the homeostatic response. However, the functional dimensions of various levels of copper exposure remain to be defined, especially as they relate to chronic disease and functional losses during aging.
In contrast, we still have no valid plasma measurements to identify copper excess. The results presented in this supplement support an ample safe range of copper intake from diet provided the gut, hepatocytes, and biliary tract are fully functional. Modeling of these results suggests that there is almost no limit to safe intake if biliary excretion remains effective. In exploring the public health relevance of copper exposure, we concluded that deficit is in fact of greater relevance than the rare occurrence of excess. Non-Wilson copper excess most frequently requires a combination of genetic metabolic defects and increased exposure. Under real-world conditions, the magnitude of copper exposure is clearly insufficient to induce detectable effects; thus, biomarkers for copper excess remain elusive. Estimated population risk from the known genetic defects makes clinical and even subclinical outcomes very uncommon. Thus, for now, the only reasonable approach to characterizing the prevalence of copper excess is the measurement of liver copper content. The challenge is finding noninvasive markers of liver copper content and assessing genetic polymorphisms in subgroups with higher liver copper under defined exposure conditions.
Genetically determined human copper excess was first described nearly 100 y ago and human copper deficiency <50 y ago. Although much has been learned, we are still unable to characterize the full spectrum of copper health effects.
