Copper deficiency is quite rare as most people get enough from the diet. However, it might be worth investigating in certain cases, such as hypothyroidism, anemia, poor immune function, and hair loss.

Read this post to learn more about the harmful effects of copper deficiency, ways to test for copper levels, and diseases related to abnormal copper metabolism.

Copper Deficiency

Frank copper deficiency is rare in humans [1].

Most adults living in developed countries obtain proper amounts of copper through their diet, supplements, and drinking water [2].

Individuals who are at risk of copper deficiency are:

  • Infants (preterm, recovering from malnutrition, fed only cow’s milk formula, with prolonged diarrhea, with cholestasis) [3, 4, 5, 6]
  • Individuals using zinc supplements or zinc-enriched dental creams [7, 8]
  • Pregnant and breastfeeding women [9]
  • Individuals with digestive problems that result in nutrient malabsorption, including Crohn’s disease, celiac disease, and(short bowel syndrome [10, 11, 12]
  • Individuals on prolonged parenteral nutrition lacking copper [13]
  • Cystic fibrosis patients [14]
  • Hypertensive individuals [15]

Causes of Copper Deficiency

1) Inadequate Copper Absorption

  • Menkes’ disease [16]
  • Weight reduction (gastric bypass) surgery [17, 18]
  • Gastrectomy (stomach removal) and esophagectomy (esophagus removal) [16, 18, 19]
  • Chronic antacid intake [20]
  • Increased zinc consumption [21, 22, 8].
  • Malabsorption syndromes (Crohn’s disease, celiac disease, short bowel syndrome) [10, 11]

2) Inadequate Copper Intake

  • Low copper infant formula or only cow’s milk formula [3]
  • Parenteral nutrition for long periods of time without copper supplementation [13]
  • Protein-calorie malnutrition [23]

3) Increased Requirements

  • Newborns, especially premature [13]
  • Pregnancy and lactation [9]

4) Excessive Copper Losses

  • Malabsorptive states [10, 11]
  • Copper chelating agents such as penicillamine [24]
  • Burns [25]
  • Nephrotic syndrome[26]

Signs of Copper Deficiency

  • Anemia
  • Neutropenia (low neutrophil levels)
  • Connective tissue degeneration
  • Growth retardation
  • Bone abnormalities
  • Pallor
  • Poor temperature control
  • Thinning, weak hair
  • Poor skin quality
  • Neurological problems (in severe cases)
  • Seizures (in severe cases) [27]

Side Effects of Copper Deficiency

1) Causes Anemia

Low copper is associated with anemia[28, 29, 30, 31].

Anemia is rapidly corrected within a few weeks with copper supplementation while oral iron had no effect [32].

Bone marrow dysplasia may be associated with copper deficiency so it is important to consider copper deficiency in the differential diagnosis of myelodysplastic syndrome (33, 34, 35).

2) Lowers Immune Function

Copper deficiency is associated with low numbers of white blood cells known as neutrophils (neutropenia) [30].

Neutrophils can’t produce superoxides and kill microorganisms as effectively in people with a copper deficiency [36].

Low copper also promotes neutrophil activation and accumulation in the liver, which contributes to the development of inflammation [37, 38, 39, 7].

Copper deficiency is known to impair macrophage function, thus increasing susceptibility to bacterial infection [40, 41].

Studies also showed that T cell growth and IL-2 production is reduced in copper deficiency [42].

3) Associated With Bone Abnormalities

Copper deficiency reduces bone strength [43, 44].

Bone abnormalities are most common in copper-deficient, low-birth-weight infants and young children [45, 46].

Copper-deficient diet in infancy could lead to brittle bones resulting in fractures, forms of (osteogenesis imperfecta, and osteoporosis) [47, 48].

A study on elderly patients showed that low (blood copper levels are associated with an increased incidence of bone fractures [49].

4) Is Linked to Neurological Disorders

Neurologic deficits have been described in adults with copper deficiency. Neurological symptoms of copper deficiency include central nervous system demyelination, polyneuropathy (nerve damage), spasticity, muscle weakness, and inflammation of the optic nerve [50, 51]. Myelopathy (disease of the spinal cord) occurs in copper-deficient individuals presents with walking difficulties [16, 52].

Neurologic manifestations are generally attributed to decreased levels of (cytochrome C oxidase and may be similar to those observed with vitamin B12 deficiency [53, 54].

These symptoms can significantly improve after oral copper supplementation [53, 55].

5) May Worsen Heart Health

Severe copper deficiency in rats altered heart function and caused enlargement of the heart which may lead to congestive heart failure [56, 57, 58].

Also, reduced dilation of blood vessels and increased bleeding were associated with reduced copper intake in rats [59, 60].

Men fed with diets low in copper experienced irregular heart rhythms [61].

Low copper may also be associated with high blood pressure. People with essential hypertension had lower blood copper levels compared to people with normal blood pressure [15].

Studies show that copper deficiency increases plasma cholesterol and “bad” LDL-cholesterol while decreasing “good” HDL cholesterol, thus increasing the risk of cardiovascular disease [62].

6) Causes Pale Skin

Copper is a cofactor of the enzyme tyrosinase, which is required for the formation of the pigment melanin. Melanin is the pigment that gives colors to the hair, skin, and eyes [63, 64].

Decreased pigmentation of the skin and general pallor of copper-deficient infants can be attributed to decreased copper levels [54].

7) May Cause Hair Loss

Copper is important for hair growth [65].

Copper concentrations were reduced in men with hair loss comparing to those without hair loss [66].

8) May Be Associated with Hypothyroidism

Copper deficiency is associated with impaired thyroid hormone metabolism [67, 68].

Copper deficiency reduced blood total T3 by 48%, blood total T4 by 21%, and whole-brain T3 by 10% in newborn rats [69].

Copper deficiency also reduces the conversion of T4 to T3, the latter of which is the more potent thyroid hormone [67].

Tests to Assess Copper Status in Humans

1) Blood Copper

Blood copper concentration is the most widely used laboratory test to evaluate copper status.

Total Blood Copper

This test measures the total amount of copper in the blood.

Normally 65 – 90% of copper in the blood is carried by a protein called ceruloplasmin [70].

Normal values for total copper range from 10 to 22 μmol/L or 65-140 mcg/dL.

High blood copper concentrations (hypercupremia) are seen in inflammation, infection, hematologic disease, pregnancy, liver disease, and diabetes [71, 72, 73, 74, 75, 76].

Low blood copper concentrations (hypocupremia) are seen in malabsorption syndromes, increased zinc consumption, patients following gastric bypass surgery, patients on prolonged parenteral nutrition without copper supplementation, and nephrotic syndrome [17, 13, 10, 26].

Free Blood Copper

This test measures the amount of copper unbound by ceruloplasmin, the copper that is “free” to accumulate in the liver and other organs.

Free serum copper ranges from 1.6 to 2.4 μmol/L.

2) Blood Ceruloplasmin

Ceruloplasmin is a protein that transports copper in the blood.

Normal serum ceruloplasmin levels: 2.83 – 5.50 μmol/L or 20 – 40 mg/dL

Ceruloplasmin is an acute-phase reactant and may be increased in stress, inflammation, hormonal changes, infection, and various chronic diseases, such as arthritis and cancer, thus its use as an indicator is limited [77, 78].

3) 24-Hour Urine Copper

The normal range for 24-hour urine copper is 20 – 50 μg per 24 hours [79].

High urine copper levels (hypercupriuria) is found in (Menkes’ disease, hemochromatosis, cirrhosis, infections, malignant diseases, inflammation, patients taking contraceptives, and pregnancy [80].

Low urine copper levels (hypocupriuria) are seen in malnutrition, malabsorption, nephrotic syndrome, and increased zinc consumption [17, 13, 10, 26].

4) Liver Copper

Liver copper concentration is the best indicator of copper status.

However, this is an invasive procedure, and it is only justified when there is evidence of liver damage as a result of copper overload [81].

Normal liver copper concentrations range from 20 to 50 μg/g of tissue.

Liver copper is elevated in Wilson’s disease and other liver disorders.

5) Copper-Containing Enzymes in Blood Cells

Determination of copper-containing enzymes in red blood cells appears to be a promising technique for assessing copper status in humans.

The enzyme activities are sensitive to changes in copper stores and are not as sensitive to factors not related to copper status, such as inflammation and infection [82].

Superoxide dismutase (SOD) Activity

Red blood cell (SOD is a good marker of copper nutrition in humans. SOD activity correlates well with blood copper [83, 84].

SOD activity changes in response to changes in copper status before any differences in blood copper or ceruloplasmin activity occur [61].

A decrease in the activity of SOD was found in patients deficient in copper and in subjects with low copper intakes.

Platelet Cytochrome-C Oxidase

Cytochrome-c activity is reduced in copper deficiency. This decrease occurs before the appearance of a change of SOD activity, suggesting this may be a more sensitive marker of copper status [81].

Sensitive indicators of copper may also include the activity of enzyme glutathione peroxidase, and concentrations of platelet copper and clotting factor VIII [84].

Inherited Diseases of Copper Metabolism

1) Wilson’s Disease

Wilson’s disease (hepatolenticular degeneration) is an inherited disorder in which excessive amounts of copper accumulate in the body, particularly in the liver and brain [85, 86].

It is caused by mutations in the (ATP7B gene which results in defective excretion of copper into bile [87, 88].

Affected individuals usually present with liver disease including chronic (hepatitis, cirrhosis, or acute liver failure) [89].

Neurological and psychiatric symptoms are more common in adults and include clumsiness, tremors, difficulty walking, speech problems, impaired thinking ability, depression, anxiety, and mood swings [89].

In many individuals, copper deposits in the eye, and forms a green-to-brownish ring, called the Kayser-Fleischer ring [90].

Typical laboratory findings include decreased blood ceruloplasmin, increased urinary copper excretion, and elevated liver copper content [85].

Treatment with penicillamine is effective in most cases while trientine and zinc are useful alternatives. Liver transplantation is required for irreversible liver damage [91].

2) Menkes’ Disease

Menkes’ disease is a rare inherited disorder caused by the absence of the(ATP7A gene [92].

This genetic mutation results in defective copper transport across intestine, placenta, and brain. The disease, therefore, resembles a severe nutritional copper deficiency despite adequate ingestion of copper [93].

Children with Menkes’ disease typically begin to develop symptoms between 2 – 4 months of age, and most children die by age 3 [54].

Symptoms arise from the deficient activity of essential cuproenzymes. It is characterized by sparse, kinky hair, failure to thrive, mental retardation, inability to control body temperature, and bone defects [94].

Laboratory findings include decreased blood copper and ceruloplasmin [91].

Severe Menkes’ disease is fatal, and no therapy is currently available. Early treatment with copper histidine may be of value in less severe cases [92].

3) Occipital Horn Syndrome

Occipital horn syndrome, also called X-linked cutis laxa, is a less severe form of Menkes’ disease that begins in early to middle childhood [95].

It is characterized by calcium deposits in the skull bone, coarse hair, and loose skin and joints [96].

Drug Interactions With Copper

If you are using any of the following medications, you should consult your physician or pharmacists prior to taking copper supplementation.

Estrogen use, both in birth control pills and replacement therapy preparations in postmenopausal women, can elevate blood levels of copper, which may be linked to increased risk of deaths from cardiovascular disease (97, 98).

Water pills (thiazide diuretics) may increase copper levels in the blood [99].

Penicillamine, a drug used to bind copper and enhance its elimination in Wilson’s disease and rheumatoid arthritis, decreases copper levels. Copper may also decrease the effects of penicillamine [24].

Allopurinol, a drug used to treat gout, forms complexes with iron, and thus may reduce copper levels and protect against heart damage [100].

Antacids may decrease copper absorption. Animal studies show that H2 blockers (cimetidine), used to treat gastric ulcers, may bind free copper ions [20].

Ethambutol, one of the primary drugs used to treat tuberculosis, leads decreased blood levels of copper [101].

Copper may enhance anti-inflammatory activity and reduce digestive side effects of nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, ibuprofen, naproxen [102, 103].

Copper Supplements

Irregular Copper Levels?

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