Ceruloplasmin Keeps Your Copper Safe
By Dicken Weatherby, N.D. and Beth Ellen DiLuglio, MS, RDN, LDN
Ceruloplasmin is a copper-containing protein produced primarily by the liver, though some is produced in lymphocytes and macrophages.[1]
It binds and carries up to 95% of circulating copper and is considered the most sensitive marker of copper deficiency.[2] <[3] Ceruloplasmin also has important antioxidant properties as an oxidase enzyme in iron, copper, and glutathione metabolism.[4] It possess nitric oxidase (NO) catalytic activity and helps regulate NO homeostasis.[5]
Measuring serum ceruloplasmin assists in diagnosing Wilson’s disease, Menkes disease, abnormal copper metabolism, and copper deficiency.
Menkes disease is a genetic disorder characterized by decreased ceruloplasmin and inability to remove copper, allowing abnormal levels of intracellular copper to build up.[6] Wilson’s disease is an inherited disorder of copper metabolism in which serum levels of ceruloplasmin may be low or normal despite increasing levels in the brain, liver, and other organs.[7]
Ceruloplasmin is an acute phase reactant and may be elevated in infection, cardiovascular disease, arthritis, and other inflammatory conditions. Elevated ceruloplasmin strongly correlates with levels of hs-CRP and is considered an independent risk factor for cardiac events. In general, elevated ceruloplasmin tends to be more common in older females with cardiovascular risk factors such as dyslipidemia and diabetes, as well as reduced renal sufficiency.[8]
As availability of copper decreases, so does ceruloplasmin. Deficiency of copper is characterized by reduction in energy production; alteration in glucose and cholesterol metabolism; accumulation of tissue iron; increased oxidative stress; altered immune cell structure and function; impairment of the electrical activity and contractility of the heart; disruption in neuropeptide synthesis and function; and aberrations in neurobehavioral stability.[9]
Ceruloplasmin plays a vital role in iron metabolism and oxidizes ferrous iron into its less toxic ferric form. It assists mobilization of iron from tissue stores to serum, where the iron can then be safely transported by transferrin.[10] Low ceruloplasmin will lead to a reduction of circulating iron and hemoglobin and contribute to anemia.[11]
Lack of ceruloplasmin, as occurs in the genetic disorder aceruloplasminemia, can lead to a toxic buildup of iron in sensitive tissues such as the pancreas, leading to diabetes in these genetically prone individuals.[12]
Ceruloplasmin has an extensive range of clinical utility and provides another tool in the optimal diagnosis toolbox. For more comprehensive assessment, serum and RBC copper should be evaluated along with ceruloplasmin. Further evaluation of inflammation including hs-CRP, ferritin, homocysteine, fibrinogen, IL-6, and neutrophil to lymphocyte ratio would be prudent as well.
Clinical Implications High |
Clinical Implications Low |
Acute phase reactant
Disease risk: Cardiovascular, dyslipidemia, diabetes, renal insufficiency
Hormonal changes
Inflammation
Medication usage
Primary biliary cirrhosis
Rheumatoid arthritis |
Acute phase reactant
Disease risk: Cardiovascular, dyslipidemia, diabetes, renal insufficiency
Hormonal changes
Inflammation
Medication usage
Primary biliary cirrhosis
Rheumatoid arthritis |
References
1. Lopez MJ, Royer A, Shah NJ. Biochemistry, Ceruloplasmin. 2020 Feb 5. [R]
2. Healy J, Tipton K. Ceruloplasmin and what it might do. J Neural Transm (Vienna). 2007;114(6):777-81. [R]
3. National Research Council (US) Committee on Copper in Drinking Water. Copper in Drinking Water. Washington (DC): National Academies Press (US); 2000. 3, Health Effects of Copper Deficiencies. [R]
4. Healy J, Tipton K. Ceruloplasmin and what it might do. J Neural Transm (Vienna). 2007;114(6):777-81. Epub 2007 Apr 4. Review. PubMed PMID: 17406962. [R]
5. Tang WH, Wu Y, Hartiala J, et al. Clinical and genetic association of serum ceruloplasmin with cardiovascular risk. Arterioscler Thromb Vasc Biol. 2012 Feb;32(2):516-22. [R]
6. Tümer Z, Møller LB. Menkes disease. Eur J Hum Genet. 2010 May;18(5):511-8. [R]
7. Yüce A, Koçak N, Ozen H, Gürakan F. Wilson's disease patients with normal ceruloplasmin levels. Turk J Pediatr. 1999 Jan-Mar;41(1):99-102. [R]
8. Tang WH, Wu Y, Hartiala J, et al. Clinical and genetic association of serum ceruloplasmin with cardiovascular risk. Arterioscler Thromb Vasc Biol. 2012 Feb;32(2):516-22. [R]
9. Hordyjewska A, Popiołek Ł, Kocot J. The many "faces" of copper in medicine and treatment. Biometals. 2014 Aug;27(4):611-21. [R]
10. Diouf I, Bush AI, Ayton S; Alzheimer's disease Neuroimaging Initiative. Cerebrospinal fluid ceruloplasmin levels predict cognitive decline and brain atrophy in people with underlying β-amyloid pathology. Neurobiol Dis. 2020 Jun;139:104810 [R]
11. Mahan, L. K., & Raymond, J. L. (2016). Krause's Food & the Nutrition Care Process, Mea Edition E-Book. Elsevier.
12. National Research Council (US) Committee on Copper in Drinking Water. Copper in Drinking Water. Washington (DC): National Academies Press (US); 2000. 3, Health Effects of Copper Deficiencies. Available from: [R]
