What is copper?
Copper (Cu) is an essential trace mineral and an important cofactor in several enzymatic and metabolic processes.
AdvertisementsCopper deficiency causes myelodysplastic syndrome (myelodysplasia) and neurologic degeneration. Cu insufficiency symptoms include anemia, neutropenia, myelopathy and peripheral neuropathy. Copper supplementation in patients with acquired copper deficiency rapidly reverses myelodysplasia and also arrests further neurologic deterioration.
Copper function and health benefits
- Cu is an important cofactor in several biochemical and enzymatic processes necessary for the function of the body.
- The enzymes, cytochrome c oxidase, Copper-zinc superoxide dismutase and dopamine beta-hydroxylase are some of the very important enzymes in which Cu is a constituent or a cofactor.
- Cu is involved in the absorption and utilization of iron.
- Cu is involved in the formation of red blood cells.
- Cu functions as an antioxidant and helps in the neutralization of free radicals.
- Cu stimulates immune response and promotes healing.
- Copper is an essential component of enzymes (cuproenzymes) regulating cellular energy production, nerve transmission, blood clotting and oxygen transport.
Sources of copper in foodsSeafood such as shellfish and shrimp are good dietary sources of Cu. Organ meat including liver, heart and kidney are good Cu containing foods. Whole grains, legumes, nuts, mushrooms, dark green leafy vegetables, coconuts, papaya and apples are good sources of this nutrient.
Copper absorption and excretionCu is absorbed from the stomach and duodenum in humans. The absorption range varies from !5% to 90% depending upon the composition of the diet and form of Cu. The presence of animal proteins, citrates and phosphates in the diet enhances absorption. Elevated levels of dietary phytates, indigestible fiber, Vitamin C, simple sugars, zinc, cadmium and iron may inhibit copper absorption. The absorbed Cu is bound to albumin, glutathione and amino acids and is carried to liver. It is incorporated into copper-proteins and released into the blood. Excess Cu is excreted into the bile, a major pathway for the excretion of this trace mineral.
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Causes of copper deficiencyCu is required by the human body in traces and several food sources contain fairly good levels of this nutrient. Hence normally dietary inadequacy of this mineral does not arise. Ingestion of excess zinc interferes with Cu absorption and utilization by the body. Acute chronic malnutrition, malabsorption, malabsorption diseases and protein energy malnutrition are causes for developing low Cu serum levels with devastating neurological symptoms.
Acquired copper deficiencyIn those under prolonged parenteral nutrition and in those who have undergone bariatric surgical procedures or gastric bypass surgery, symptoms of insufficiency of Cu manifest. The symptoms manifest as myelodysplasia and neurologic deterioration when Cu is not supplemented.
B.P. Goodmana et al. reported a case of myeloneuropathy in a 53-year-old woman. She also suffered from anemia. Serum copper and ceruloplasmin levels were found to be markedly decreased. The patient did not have a history of gastric bypass surgery, malnutrition or excess zinc ingestion. However the patient had hyperzincemia. The researchers hypothesized that copper deficiency in such patients is likely due to a luminal copper transport or trafficking defect. It is possibly a case of copper binding to metallothionein (zinc stimulated) in intestinal enterocytes and subsequent loss into the intestinal lumen.
Inherited copper deficiencyMenkes disease is a disorder of copper malabsorption, which develops in infants, manifesting with neurologic and systemic symptoms. Menkes syndrome is an X-linked inherited disorder. It is characterized by sparse, kinky hair, low body weight and failure to thrive. Children with Menkes disease develop symptoms during infancy and do not live past three years of age. It is caused by mutations in the ATP7A gene. These mutations result in poor regulation of Cu levels in the body. The activity of several cuproenzymes gets reduced affecting the structure and function of organ systems.
Occipital horn syndrome is a X-linked inherited form of cutis laxa. Occipital horn syndrome is also caused by mutations in the ATP7A gene. These mutations result in poor regulation of copper levels in the body. This is considered milder form of Menkes syndrome. The symptoms are, sagging and inelastic skin, droopy appearance, extremely wrinkled skin, coarse hair, wedge-shaped calcium deposits in the occipital bone at the base of the skull and loose joints.
Symptoms of copper deficiencyThe symptoms of copper inadequacy manifest on several organs, including skin and skin appendages, skeletal and soft muscles, bone and connective tissues, cardiovascular system, respiratory system and nervous system. Some of the connected symptoms and manifestations are:
- limb numbness,
- skin sores,
- hair loss,
- proximal weakness,
- oxidative damages,
- unsteady gait,
- poor nerve conductivity,
- absence of vibration sense,
- severe proprioceptive deficiency,
- profound sensory ataxia,
- respiratory failure,
- bilateral optic neuropathy,
- bone and connective tissue abnormalities and
- cardiovascular diseases.
Diagnosis of copper deficiencyDecrease in serum copper and ceruloplasmin levels indicates the condition. A delayed diagnosis can lead to irreversible neurological disability and symptoms. The neurological symptoms may be present without the hematologic manifestations.
Copper deficiency diseasesLow serum levels of Cu can lead to several disease conditions with hematological and neurological manifestations.
Hematological manifestationsHematological diseases such as myelodysplasia (ineffective production of all blood cells), anemia (decrease in the amount of red blood cells), leukopenia (low white blood cell count), neutropenia (low count of neutrophils) and thrombocytopenia (low blood platelets) are caused when there is deficiency of copper in the body system. All these disease symptoms totally resolve on Cu supplementation therapy.
Neurological manifestationsNeurological diseases such as myelopathy, peripheral neuropathy, and optic neuropathy with devastating symptoms and consequences are caused due to deficiency of copper in the blood serum.
Myelopathy (disease of the spinal cord) linked to copper deficiency was first described by Schleper B, et al.(J Neurol. 2001 Aug; 248 (8): 705 - 6) in 2001. Patients with myelopathy have the typical symptom of severe tetraparesis (muscle weakness affecting all four limbs). The symptoms manifest as difficulty in walking caused by irregular muscle coordination due to degenerative damage of the spinal cord.
Peripheral and optic neuropathy
Peripheral neuropathy is another common symptom of copper deficiency. The initial symptoms are painful paraesthesias (a sensation of tingling, tickling, pricking, or burning of skin). The condition may progress into diminished or abnormal upper and limb reflexes. The sensation to light touch, pin prick and vibration may be gradually lost. Proprioception may get markedly reduced leading to the risk of fall and injury. In some patients low levels of copper causes optic neuropathy and nerve fiber layer loss manifesting as gradual vision loss and color vision loss.
Treatment of copper deficiencyInsufficiency of Cu in the body is treated by parenteral and oral copper replacement to achieve normal serum Cu levels. The hematologic manifestations of low Cu levels and the associated symptoms are rapidly reversible after Copper supplementation therapy. However, the neurologic deterioration may, at best, stabilize and the patient may remain with debilitating neurological symptoms. In a few cases, improvement is observed in copper deficiency related sensory symptoms with Cu supplementation.
1.Prohaska JR. Impact of copper deficiency in humans. Ann N Y Acad Sci. 2014 May;1314:1-5. doi: 10.1111/nyas.12354.
2.Imataki O, Ohnishi H, Kitanaka A, Kubota Y, Ishida T, Tanaka T. Pancytopenia complicated with peripheral neuropathy due to copper deficiency: clinical diagnostic review. Intern Med. 2008;47(23):2063-5. Epub 2008 Dec 1.
3.B.P. Goodmana, B.W. Chongb, A.C. Patelb, G.P. Fletcherb, B.E. Smitha. Copper Deficiency Myeloneuropathy Resembling B12 Deficiency: Partial Resolution of MR Imaging Findings with Copper Supplementation. AJNR Am J Neuroradiol. 2006 Nov-Dec;27(10):2112-4.
4.Spain RI1, Leist TP, De Sousa EA. When metals compete: a case of copper-deficiency myeloneuropathy and anemia. Nat Clin Pract Neurol. 2009 Feb;5(2):106-11. doi: 10.1038/ncpneuro1008.
5.Yarandi SS, Griffith DP, Sharma R, Mohan A, Zhao VM, Ziegler TR. Optic neuropathy, myelopathy, anemia, and neutropenia caused by acquired copper deficiency after gastric bypass surgery. J Clin Gastroenterol. 2014 Nov-Dec;48(10):862-5. doi: 10.1097/MCG.0000000000000092.