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Methods of assessment of copper status in humans: a systematic review^1,2,3,4,5

¹ From the School of Medicine, Health Policy and Practice, University of East Anglia, Norwich, United Kingdom (LJH, KA, LH, AC, and SJF-T); the Institute of Food Research, Norwich Research Park, Colney, Norwich, United Kingdom (LJH); and the Peninsula Technology Assessment Group (PenTAG), Peninsula Medical School, Universities of Exeter and Plymouth, Exeter, United Kingdom (KA).

² This article does not necessarily reflect the views of the Commission of the European Communities and in no way anticipates the future policy in this area.

³ Presented at the EURRECA workshop "Biomarkers of Micronutrient Status," held in Sveti Stefan, Montenegro, 9 June 2008.

⁴ Supported by the Commission of the European Communities, specific RTD Programme, "Quality of Life and Management of Living Resources," within the 6th Framework Programme (contract no. FP6-036196-2 EURRECA: EURopean micronutrient RECommendations Aligned).

⁵ Address correspondence to LJ Harvey, School of Medicine, Health Policy and Practice, University of East Anglia, Norwich, NR4 7TJ, United Kingdom. E-mail: linda.harvey{at}uea.ac.uk.

Background: The assessment of dietary adequacy of copper is constrained by the absence of recognized copper status biomarkers.

Objectives: The objectives were to systematically review the usefulness of copper status biomarkers and identify those that reflected changes in status over 4 wk.

Design: The methods included a structured search on Ovid MEDLINE, EMBASE (Ovid), and Cochrane databases to October 2007, followed by the use of formal inclusion/exclusion criteria, data extraction, validity assessment, and meta-analysis.

Results: A total of 16 studies (288 participants) were included in the review, with data on 16 possible copper biomarkers. All of the included studies were small and at high risk of bias. Data for serum copper suggested its value as a biomarker, reflecting changes in status in both depleted and replete individuals, although these changes were smaller in the latter. Total ceruloplasmin protein is related to copper status but reflects changes in highly depleted individuals only. Erythrocyte superoxide dismutase and urinary deoxypyridinoline are not useful biomarkers, but there were insufficient data to draw firm conclusions about plasma, erythrocyte, and platelet copper; leukocyte superoxide dismutase; erythrocyte, platelet, and plasma glutathione peroxidase; platelet and leukocyte cytochrome-c oxidase; total glutathione; diamine oxidase; and urinary pyridinoline. The paucity of data prevented detailed subgroup analysis.

Conclusions: Despite limited data, serum copper appears to be a useful biomarker of copper status at the population level. Further large studies with low risk of bias are needed to explore the effectiveness of other biomarkers of copper status and the relation between biomarker responsiveness, dose, and period of supplementation.

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