Mineral Biomarkers: RBC Copper

Optimal Takeaways

Copper is an essential trace mineral with important roles in iron metabolism, red blood cell health, energy generation, antioxidant systems, hormone metabolism, and immunity. Measuring copper at the RBC level provides information about what is available intracellularly and may be a better reflection of whole-body copper than serum levels. Insufficiency of copper contributes to anemia, oxidative stress, and compromised cognition. Excess copper can compromise zinc status and may also be associated with obesity, diabetes, heart disease, nephrotic syndrome, cognitive dysfunction, and altered antioxidant status.

Standard Range: 0.53 – 0.91 mg/L (8.34 – 14.32 umol/L)

The ODX Range: 0.53 – 0.91 mg/L (8.34 – 14.32 umol/L)

Low RBC copper levels are associated with anemia, decreased erythropoiesis, neutropenia, thrombocytopenia, leukopenia, hypopigmentation of hair and skin, malabsorption, celiac disease, inflammatory bowel disease, neurologic dysfunction, oxidative stress, decreased ceruloplasmin, excess zinc intake, Menkes disease, and use of proton pump inhibitors (Gropper 2021).

Copper insufficiency can cause iron overload, cirrhosis, platelet aggregation, inflammation, and increased glycation end-products and may be the leading cause of ischemic heart disease (DiNicolantonio 2018).

Insufficiency may also contribute to impaired energy generation, altered glucose and cholesterol metabolism, immune cell dysfunction, disrupted cardiac electrophysiology and contractility, compromised neuropeptide production and processing (Hordyjewska 2014), myeloneuropathy, pseudotabes (Marotta 2021), ataxia, and increased LDL/HDL cholesterol ratio (Burkhead 2022).

High RBC copper levels may be associated with cognitive deficits (Lam 2008), diabetes (Olaniyan 2012), obesity (Gu 2020), nephrotic syndrome (Dwivedi 2009), cardiovascular disorders, and heart failure (Huang 2019).

Overview

Copper is an essential trace mineral in several metabolic functions, including iron metabolism, energy production, antioxidant activity, blood clotting, immunity, neurotransmitter metabolism, and collagen and melanin production. Most circulating copper is found in ceruloplasmin, an important free radical scavenger that is likely the first biomarker to decline with insufficient copper availability (Gropper 2021).

However, red blood cell copper may better assess total body copper and what is available “in the pantry” for the long term. Approximately 60% of copper in RBCs is incorporated into Cu-Zn-superoxide dismutase. Copper stores are likely depleted once overt clinical manifestations of deficiency appear, such as anemia, neutropenia, depigmentation of hair and skin, bone changes, and physical and mental retardation. Earlier research of 49 healthy adults observed a mean RBC copper concentration of 0.7 mg/L (11 umol/L) (Hatano 1982).

Levels of RBC copper may decline or be decreased during moderate to heavy physical activity or training, which may compromise performance. One study of 76 men found that those undergoing moderate or high-intensity training had significantly lower RBC copper concentrations than those sedentary subjects. Researchers recommend monitoring RBC minerals in physically active individuals (Maynar 2020).

References

DiNicolantonio, James J et al. “Copper deficiency may be a leading cause of ischaemic heart disease.” Open heart vol. 5,2 e000784. 8 Oct. 2018, doi:10.1136/openhrt-2018-000784

Gropper, Sareen S.; Smith, Jack L.; Carr, Timothy P. Advanced Nutrition and Human Metabolism. 8^th edition. Wadsworth Publishing Co Inc. 2021.

Gu, Kunfang et al. “The Relationship Between Serum Copper and Overweight/Obesity: a Meta-analysis.” Biological trace element research vol. 194,2 (2020): 336-347. doi:10.1007/s12011-019-01803-6

Hatano, S et al. “Copper levels in plasma and erythrocytes in healthy Japanese children and adults.” The American journal of clinical nutrition vol. 35,1 (1982): 120-6. doi:10.1093/ajcn/35.1.120

Hordyjewska, Anna et al. “The many "faces" of copper in medicine and treatment.” Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine vol. 27,4 (2014): 611-21. doi:10.1007/s10534-014-9736-5

Huang, Lei et al. “Association between serum copper and heart failure: a meta-analysis.” Asia Pacific journal of clinical nutrition vol. 28,4 (2019): 761-769. doi:10.6133/apjcn.201912_28(4).0013

Lam, P K et al. “Plasma trace elements and cognitive function in older men and women: the Rancho Bernardo study.” The journal of nutrition, health & aging vol. 12,1 (2008): 22-7. doi:10.1007/BF02982160

Marotta, Dario A et al. “Myeloneuropathy in the Setting of Hypocupremia: An Overview of Copper-Related Pathophysiology.” Cureus vol. 13,7 e16254. 8 Jul. 2021, doi:10.7759/cureus.16254

Maynar, M et al. “Erythrocyte concentrations of chromium, copper, manganese, molybdenum, selenium and zinc in subjects with different physical training levels.” Journal of the International Society of Sports Nutrition vol. 17,1 35. 9 Jul. 2020, doi:10.1186/s12970-020-00367-4

Olaniyan, O. O., et al. "Serum copper and zinc levels in Nigerian type 2 diabetic patients." African Journal of Diabetes Medicine Vol 20.2 (2012).