Copper deficiency

Copper deficiency is a rare condition when the lack of copper in the body is observed and it causes various hematological and neurological symptoms.

Copper deficiency: Description

Copper is necessary for the production and functioning of the various enzymes such as cytochrome C oxidase, which takes part in cellular respiration and oxidative phosphorylation, Cu/Zn dismutase, which provides antioxidant defense.

Copper-containing enzymes are essential for the structure and function of the connective tissue – bones, skin, hair, blood vessels and the nervous system. Impaired iron transport results in anemia. Hephaestin – a copper containing ferroxidase enzyme of the duodenal mucosa oxidizes iron and helps to transfer it through the basolateral membrane into the systemic circulation.

Ceruloplasmin is required to mobilize iron from the reticuloendothelial cells into the plasma. This enzyme also oxidizes iron from its ferrous state in the ferric form – this process is necessary to enable the iron binding.


copper deficiency

Causes and risk factors

Copper deficiency is very rare, as long as many foods contain copper. However, copper deficiency may develop due to malabsorption (above all in the duodenum) . A low copper level may be caused by nephrotic syndrome or Menkes disease (a genetic X-linked recessive disorder when the mutations in ATP7A protein gene are detected and results in the neurodegeneration).

Risk factors include previous upper gastrointestinal surgery, excessive intake of vitamin C supplements (1500 mg/day), zinc overload (150 mg/day or above) and malabsorption syndromes, which impair copper absorption in the duodenum. 

Read also: Chromium deficiency

Recommended daily intake and the sources

The Recommended Daily Allowance (RDA) for copper is 900 micrograms for adolescents and adults. RDAs are higher for pregnant and lactating women with 1 mg and 1.3 mg, respectively.

The sources of copper are:

  • seeds;
  • shiitake mushrooms;
  • avocado;
  • organ meats (beef liver);
  • nuts (cashew and almonds);
  • seafood;
  • semi-sweet chocolate.

Some amounts of copper are also found in the water.


Blood symptoms of copper deficiency include:

  • anemia (micro-, normo- or macrocytic). Anemia leads to tiredness, paleness and fatigue;
  • neutropenia (decreased amount of neutrophiles);
  • thrombocytopenia is possible, but not common (low blood platelets);

Neurologic symptoms include:

  • myelopathy characterized by the difficulties walking (due to sensory ataxia) caused by the dysfunction of the spinal cord. A person experiences tremors;
  • peripheral neuropathy- These symptoms include diminished limb reflexes, sometimes abnormal limb reflexes, diminished vibration and touch sensation, reduced proprioception;
  • optic neuropathy characterized by the impaired vision.


Serum copper and ceruloplasmin along with 24-hour urine copper are measured to verify the diagnosis. A blood test and bone marrow biopsy is necessary to estimate anemia.

Bone marrow aspirate presents with dysplasia of blood cell precursors and the presence of ring sideroblasts (a specific erythroblasts which contain multiple iron granules around the nucleus). Cytoplasmic vacuoles within red and white cell precursors are seen in cases of copper deficiency.

Imaging examinations such as ultrasonography, CT/MRI may also be performed, subacute combined degeneration may be seen.

Reference values

Copper reference ranges are the following:

  • Free serum copper: 10-15μg/dL
  • Total copper: 63.7-140.12 μg/dL
  • Serum ceruloplasmin: 18-35 μg/dL
  • 24-hour urine copper:  20-50 μg
  • Liver copper: 20-50 μg/g of tissue


Copper deficiency is typically treated with oral copper supplements or intravenous copper injections. Copper histidine (350-500 µg/day or every other day) is thought to be the most effective form of copper.

Menkes disease is incurable. However, appropriate and careful medical care with copper medications is known to extend life span up to 13 years or even more.