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Human biomarkers for measuring copper intake and status

Serum copper concentration reflects changes in both depleted and replete individuals and may have benefit as a biomarker (9). However, most copper in the body is bound to proteins: 65-71% is bound to ceruloplasmin, the glycoprotein enzyme involved in iron metabolism, and 15-19% to albumin (7). Total ceruloplasmin reflects changes only in highly depleted individuals (9), and therefore may not have use as a population biomarker. Copper present free in serum and/or bound to amino acids may also be useful to measure; some reports suggest a link between an excessive free copper fraction and degenerative health effects due to oxidation and a depletion of antioxidant reserves (7, 10). Copper may also be assessed in human milk samples, which may be an accessible specimen in population studies involving lactating women and infants (11), and in plasma, though this method appears to be more infrequently used (9).

Other possible biomarkers are plasma, platelet, and erythrocyte copper, and other proxy biomarkers including platelet and leucocyte cytochrome c oxidase, total glutathione and urinary pyridinoline (9). These biomarkers are not included here.


Atomic Absorption Spectrometry (AAS): Suitable for human serum, plasma, milk (see method in reference (12), Silvestre et al Food Chem 2000 68:95-99)  and bones (see method in reference (13), Baranowska et al. 1995 Sci Total Environ 159:155-162).

Instrument parameters are usually instrument-dependent. An example for AAS is provided by reference (7).

Inductively-coupled plasma dynamic reaction cell mass spectrometry (ICP-DRC-MS): Suitable for plasma, serum, and milk samples for assessment of total copper (For method, see CDC SOP).

Inductively-coupled plasma atomic emission spectrometry (ICP-AES): Suitable for:

Measurement of ceruloplasmin in serum or urine: Measurement can be conducted using a kit, e.g. this one by ThermoFisher Scientific.

Confounding factors

Results should be interpreted with respect to factors that influence the concentration of copper in various body pools. Several physiological functions can affect copper content and the activity of ceruloplasmin in blood, including acute phase response to infection and inflammation, pregnancy and other hormonal perturbations, some carcinogens, and smoking (2). Circulating copper may be especially high during inflammation and may not represent cellular concentrations of cuproenzymes (2).

Quality control and technical assistance

Laboratory accreditation and validation

For laboratory accreditation and validation schemes, see the OpeN-Global laboratory accreditation page.

Technical assistance

For questions on copper methods or for technical assistance, please contact: 


Dr Daniela Hampel, PhD
Project Scientist
USDA/ARS Western Human Nutrition Research Center
Department of Nutrition, University of California Davis

Email: or