Mineral Biomarkers: Ceruloplasmin

Optimal Takeaways

Ceruloplasmin is a protein produced in the liver and utilized for copper transport, iron oxidation, and antioxidant activity. Low levels indicate a copper deficiency or genetic aceruloplasminemia, while elevated levels are associated with copper toxicity, zinc deficiency, inflammation, infection, cardiovascular disease, and iron overload.

Standard Range: 19.00 – 39.00 mg/dL (1.90 – 3.90 umol/L)

The ODX Range: 18.00 – 21.00 mg/dL (1.80 – 2.10 umol/L)

Low ceruloplasmin is associated with copper deficiency (Gropper 2021), Wilson’s disease, Menke’s disease (Raymond 2021), aceruloplasminemia, malnutrition, and low protein intake (Lopez 2021).

High ceruloplasmin may be associated with cancer, rheumatoid arthritis (Raymond 2021), decreased nitric oxide activity, atrial fibrillation, heart failure, endothelial dysfunction, neurodegenerative disease (Hammadah 2014), and long-term adverse cardiac events (Tang 2012). As an acute-phase reactant, elevated ceruloplasmin is associated with infection, inflammation, stress, trauma, arthritis, and chronic disease (Hordyjewska 2014). Elevated ceruloplasmin may also be associated with copper toxicity, zinc deficiency, pregnancy, lymphoma, angina, Alzheimer’s disease, schizophrenia, and OCD (Lopez 2021).

Overview

Most circulating copper is bound to ceruloplasmin, a glycoprotein that delivers copper to cells and assists in copper excretion from the body. Ceruloplasmin participates in iron metabolism by oxidizing ferrous iron to ferric iron, making it available to bind to transferrin and be mobilized from tissues into the blood. Without ceruloplasmin, iron accumulates in the liver (Hordyjewska 2012).

Ceruloplasmin’s oxidation of iron helps inhibit the use of iron by pathogenic microbes. Ceruloplasmin oxidizes other minerals, including manganese, and may help eliminate excess superoxide free radicals generated during inflammation and infection (Gropper 2021).

While low ceruloplasmin levels can contribute to decreased antioxidant activity and increased oxidative stress, elevated ceruloplasmin may be associated with heart disease. One large prospective cohort study of 4,177 subjects with coronary artery disease but no evidence of MI found that higher ceruloplasmin was strongly correlated with higher hs-CRP and was associated with dyslipidemia, diabetes, and poorer renal function. Those with a ceruloplasmin of 22 mg/dL (220 umol/L) and above had the greatest risk of major adverse cardiovascular events over the 3-year follow-up period (Tang 2012).

Another study of 890 patients with stable heart failure found that ceruloplasmin above a cut-off of 21.5 mg/dL (215 umol/L) was significantly associated with increased 5-year mortality independent of traditional CVD risk factors (Hammadah 2014).

References

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

Hammadah, Muhammad et al. “Prognostic value of elevated serum ceruloplasmin levels in patients with heart failure.” Journal of cardiac failure vol. 20,12 (2014): 946-52. doi:10.1016/j.cardfail.2014.08.001

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

Lopez, Michael J., et al. “Biochemistry, Ceruloplasmin.” StatPearls, StatPearls Publishing, 13 December 2021.

Raymond, Janice L., et al. Krause and Mahan's Food & the Nutrition Care Process. Elsevier, 2021.

Tang, W H Wilson et al. “Clinical and genetic association of serum ceruloplasmin with cardiovascular risk.” Arteriosclerosis, thrombosis, and vascular biology vol. 32,2 (2012): 516-22. doi:10.1161/ATVBAHA.111.237040