Copper is an essential – vitally important - trace element required for survival by all organisms. Its essentiality derives from the fact that it is incorporated into a large number of proteins for both catalytic and structural purposes. 1 At least 20 enzymes have a functionality that is dependent on copper, although this is not always clearly known.
These include:
• superoxide dismutase (SOD), an enzyme present in most human cells which protects the body from oxidative damage. Concentrations are high in brain, thyroid and liver tissue.
• lysyl oxidase, an enzyme involved in cross-linking mechanisms required for connective tissue stability. Reduced activity of this enzyme is linked to numerous structural abnormalities in many tissues including the bone and cardiovascular system.
• cytochrome c oxidase, an enzyme which catalyses the reduction of oxygen to water, an essential step in cellular respiration. Activity is highest in the heart and high in the brain and liver.
The essentiality of copper has been recognised since 1928, but is best illustrated by Menkes disease, a very rare genetic disorder, which results in entrapment of copper in the cells of the intestine. The clinical features of Menkes include impaired mental development, abnormalities in connective tissue development (skin, bone and hair), general failure to thrive and early death in childhood. 2 Indeed, this genetic disease points out the essentiality of copper for optimal development. Further insights into the role of copper have come from investigating the effects of depletion and supplementation in animal models and humans. Such investigations show that copper has a wide range of essential functions critical for normal physiological function and good health. These are reviewed below:
Protection against oxidative stress
Copper has an essential antioxidant role through superoxide dismutase combating oxidative stress by helping to neutralize free radicals that would otherwise cause severe cellular damage. Evidence that copper deficiency leads to increased lipid oxidation continues to accumulate from animal studies.3 Similarly, studies show that copper supplementation can increase the oxidative defences of people. 4 5 Many of the consequences of copper deficiency are thought to be associated with increased oxidative stress.
The brain and central nervous system
Copper appears to play multiple roles in the health of the central nervous system, particularly brain tissue. Copper is required for the formation and maintenance of myelin, the protective layer covering neurons. Copper-dependent enzymes are also necessary for the synthesis of neurotransmitters – the chemical messengers that allow communication between nerve cells.6
Cardiovascular health
A large body of evidence suggests that copper has essential structural and functional roles throughout the cardiovascular system.
Copper is important for the structural integrity of the heart and blood vessels. Crosslinking of arterial collagen and elastine require the copper-dependent enzyme lysyl oxidase. Among the many documented anatomical changes produced by copper deficiency are cardiac enlargement, arteries with smooth muscle degeneration and ventricular and coronary artery aneurysms (abnormal swelling of a portion of the blood vessel caused by weakness of the vessel wall). 7
Many functional aspects of the heart and circulation are adversely affected by copper deficiency. Men fed a diet low in copper experience cardiac arrhythmias – abnormal electrical rhythms. Copper also affects normal cholesterol metabolism: healthy adults fed a diet low in copper show increased levels of LDL cholesterol (the bad type) and reduced levels of HDL cholesterol (the good type). 8 9 Low copper intake has also been shown to adversely affect glucose metabolism and blood pressure regulation.10 Copper is also needed for normal blood clotting. The clotting factors V and VIII depend on copper for normal function, and studies show that atrial thrombosis is more frequent in animals fed copper-deficient diets. 11 Furthermore, patients who died from myocardial infarction (MI) have been shown to have significantly lower copper concentration in heart tissue than those who died of other causes. 12 However, it is not known if the copper deficiency caused the MI or was the result of underlying heart disease.
Many of the undesirable changes observed in humans occur with diets containing close to 1 mg of copper per day in humans. This has lead to suggestions that marginal copper deficiency may play a role in the development of cardiovascular disease. 13
Iron transport and anaemia
Copper also promotes normal red blood cell formation. It helps convert iron to its ferric form – the most useful type – and also helps transport iron to and from tissues. Copper deficiency can result in anaemia and tissue iron overload. 14 In fact, anaemia is one of the most common clinical manifestations of copper deficiency. 1
Bone health
Copper also has an important role in the health of the skeleton, and through the action of lysyl oxidase, is essential for the formation of strong flexible connective tissue needed to give bone its strength. Bone abnormalities are associated with copper deficiency in lowbirth-weight infants and in young children. Higher copper blood levels have been linked with higher bone mineral density of the lumbar spine in a cross-sectional study in postmenopausal women; 15 and decreased blood levels of copper have been observed in people with bone fractures. 16
Furthermore, one recent study shows that a dietary copper intake of 0.7 mg per day for just six weeks significantly increases the rate of bone resorption [an indicator of increased bone turnover] in healthy adult males aged between 20 and 59 years. This effect was reversed during a subsequent six-week period of copper supplementation (6.0 mg per day). 17
Immune function
The immune system requires copper to perform a number of functions. 18 Copper deficiency has a profound effect on certain white cell populations (neutrophils and macrophages); and eutropenia (a reduction in neutrophil count) may be a clinical sign of copper deficiency in humans. 19 Immune function has been investigated in copperdeficient infants before and after copper supplementation. The phagocytic activity of certain white blood cells - their ability to engulf foreign material - increased after copper supplementation.20 Other research in healthy young men fed a diet of 0.66 mg copper per day highlighted a decrease in the proliferation of other immune cells (peripheral blood mononuclear cells) during this time.21 Copper deficiency has also been associated with an increased incidence of severe respiratory infections in infants. 22
Copper in diet
Copper is an essential nutrient required for the functioning of many enzymes in the body. This means the body demands regular intake of dietary copper in order to maintain health. Various national and international authorities have defined standards for copper intake at levels judged to be adequate for maintaining health:
• The Standing Nordic Committee on Foods set the recommended dietary allowance
(RDA) of copper at 2 mg a day for an adult in 1996.23
• The EU population reference intake for copper is 1.1 mg/day.24
• The US National Academy of Sciences issued its first RDA for copper in 2001 recommending that adults consume 0.9 mg of copper every day, pregnant women 1.0 mg and nursing mothers 1.3 mg. 25 NAS also established a Tolerable Upper Limit for copper of 10 mg/day.
• The World Health Organization estimates the lower limit of the acceptable range of oral intake (AROI) for copper is 20 μg/kg of body weight for adults and about 50 μg/kg of body weight per day for infants.26 For a normal healthy adult (weighing 50-70 kg), this amounts to 1.0 to 1.4 mg/day.
Dietary sources of copper
|
Food
|
Mean copper content [mg/kg]32
|
|
Beef
|
1.1
|
|
Lamb
|
1.6
|
|
Beef liver
|
39
|
|
Beef kidney
|
3.7
|
|
Apples
|
0.25
|
|
Bananas
|
0.95
|
|
Potatoes
|
0.96
|
|
Carrots
|
0.61
|
|
Lettuce
|
0.72
|
|
Cod
|
0.19
|
|
Flour
|
1.5
|
|
Cocoa powder
|
36.4
|
|
Cow’s milk
|
0.06
|
There may be a significant number of individuals with marginal copper intakes. Calculations based on surveys of 849 individual diets from Europe and North America, in which the copper content was measured by chemical analysis, indicated that more than 30 % of diets provide less than 1.0 mg of copper per day.27 Data from a study conducted in Ireland showed that 23 % of women and 8% of men had mean daily intakes below the average requirement.28 Indeed a report published by the World Health Organization recently said that based on available data on human exposure worldwide, but particularly in Europe and the Americas, there is a greater risk of health effects from deficiency of copper intake than excess. 29
The failure of many diets to meet daily copper requirements reflects the fact that the richest sources of copper are not typically consumed in Western diets. Consequently, the copper provided by plant-based foods and dairy products contribute proportionately more to copper intake than would be expected considering their relatively low content and poor availability. Plant foods in general provide about 60% of the copper in Western diets. 30 Several studies show that copper intake is higher in vegetarian and vegan diets.31
Who is at risk of copper deficiency?
The nutritional concept of empty calories is far from new; few foods are as free of copper as fats and oils. Consequently, eating a diet that is rich in highly processed convenience and/or fast foods and low in plant foods puts individuals in danger of suboptimal copper intake. Processed grains, for example, contain less copper than whole grains because much copper is removed with the bran fraction and seed coat.Other groups at high risk of copper deficiency include:
• Premature babies because foetuses bank copper during the latter months of pregnancy
• Infants recovering from malnutrition associated with chronic diarrhoea
• Pregnant and nursing women particularly if they avoid copper-rich foods
• Individuals with chronic digestive problems who may be unable to absorb sufficient amounts of copper
• Older adults with reduced dietary intake and compromised nutrient bioavailability resulting from the use of multiple medications and increased excretion
• People using excessive amounts of iron and zinc supplements
What risks are associated with copper deficiency?
Copper is essential for life. Although rare, severe or clinically defined copper deficiency is associated with anaemia, neutropenia (a reduction in white blood cell neutrophil count) and bone abnormalities, including fractures.
References
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2 Menkes JH et al A sex-linked recessive disorder with retardation of growth,
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24 Scientific Committee for Food. Nutrient and Energy Intakes for the European Community. Luxembourg: "Office for Official Publications of the European Communities, 1993.
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