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Copper


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Copper

Background

Copper is a mineral that occurs naturally in many foods, including vegetables, legumes, nuts, grains and fruits, as well as shellfish, avocado, and beef (organs such as liver). Because copper is found in the earth's crust, most of the world's surface water and ground water used for drinking purposes contains small amounts of copper. Water obtained from copper pipes contains copper.

Copper is involved in numerous biochemical reactions in human cells. Copper is a component of multiple enzymes, is involved with the regulation of gene expression, mitochondrial function/cellular metabolism, connective tissue formation, as well as the absorption, storage, and metabolism of iron. Copper levels are tightly regulated in the body. Most copper is excreted in bile with minimal reabsorption in the gastrointestinal tract (and minimal urinary excretion).

The U.S. RDA (recommended daily allowance) for copper is 900 mcg for adults; 1000 mcg for pregnant women; 1300 mcg for nursing women; 890 mcg for adolescents 14-18 years old; 700 mcg for children 9-13 years old; 440 mcg for children 4-8 years old; 340 mcg for children 1-3 years old; 220 mcg for infants 7-12 months old; and 200 mcg for infants 0-6 months old. Surveys suggest that most Americans consume less than the RDA for copper each day. Up to 3000-5000 mcg daily appears to be safe for consumption in children older than 3 years, and up to 10,000 mcg in adults. The average level of copper stored in the body is between 50-120mg (50,000-120,000 mcg), and most is contained in the liver.

Copper toxicity is rare in the general population. Excess copper consumption may lead to liver, kidney, or neurologic damage. Excess dosing may lead to symptoms including weakness, abdominal pain, nausea, vomiting, and diarrhea, with more serious signs of acute toxicity including liver damage, kidney failure, pleural damage, coma, and death (which can occur with ingestion of doses in the range of 1 gram of copper sulfate) (1;2;3;4). Other medical problems associated with copper toxicity may include anxiety, depression, fatigue, learning disabilities, memory lapses, diminished concentration, insomnia, seizure, delirium, stuttering, hyperactivity, arthralgias, myalgias, hypertension, gingivitis, dermatitis, discoloration of skin/hair, preeclampsia, postpartum psychosis, or weight gain.

Wilson's disease is a genetic disorder in which the body cannot rid itself of copper, resulting in deposition in organs and serious consequences such as liver failure and neurologic damage (5). Obstruction of bile flow, contamination of dialysis solution (in patients receiving hemodialysis for kidney failure), Indian childhood cirrhosis, or idiopathic copper toxicosis are other rare causes of potentially dangerous excess copper levels. Such individuals should be followed closely by a physician and nutritionist.

Copper deficiency can occur in infants fed only cow-milk formulas (which are relatively low in copper content), premature/low-birth weight infants, infants with prolonged diarrhea or malnutrition, individuals with malabsorption syndromes (including celiac disease, sprue, or short bowel syndrome), cystic fibrosis, in the elderly (6), or those receiving intravenous total parenteral nutrition (TPN) or other restrictive diets. Such individuals may require supplementation with copper and other trace elements. Copper deficiency can cause sideroblastic anemia, hypercholesterolemia (7;8), or deficiencies of copper-dependent coagulation factors such factor V, factor VIII, and fibrinogen (9;10;11;12). In theory, growth inhibition may occur (13;14).

Medicinal use of copper compounds dates to Hippocrates in 400 B.C. Bacterial growth is inhibited on copper's surface, and hospitals historically installed copper-alloy doorknobs and push-panels as a measure to prevent transmission of infectious disease.

Synonyms

Copper supplements are available as copper acetate, cupric oxide, copper gluconate, copper sulfate, copper amino acid chelates , cupric sulfate, copper sebecate, cuivre, organic copper, inorganic copper and elemental copper.

Brands: Cupri-Pak, Availa-Cu.

Combination products: Centrum Forte: [iron (10mg), magnesium (100mg), zinc (15mg), calcium (162mg), copper (2mg), manganese (5mg)], PerMamma [zinc sulfate, copper sulfate, potassium iodine], Renal-specific Micronutrient [vitamins C, E, K and B complex, copper, zinc], Pediatric Renal Seravit [vitamins, A, E, D, C and B complex with trace minerals], Victory [soluble copper, peroxide compound, and a cationic agent].

Evidence

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Uses based on scientific evidenceGrade*Copper deficiency
Copper deficiency may occur in infants fed only cow-milk formulas (which are relatively low in copper content), premature/low-birth weight infants, infants with prolonged diarrhea or malnutrition, individuals with malabsorption syndromes (including celiac disease, sprue, or short bowel syndrome), cystic fibrosis, in the elderly (6), or those receiving intravenous total parenteral nutrition (TPN) or other restrictive diets. Such individuals may require supplementation with copper (and other trace elements). Copper deficiency can cause sideroblastic anemia, hypercholesterolemia (7;8), growth abnormalities, bone maldevelopment, or deficiencies of copper-dependent coagulation factors such factor V, factor VIII, and fibrinogen (9;10;11;12). Cases of known/suspected copper deficiency should be evaluated and managed by a physician and nutritionist.

A

Alzheimer's disease prevention
Conflicting study results report that copper intake may either increase or decrease the risk of developing Alzheimer's disease. Additional research is needed before a recommendation can be made.

C

Sideroblastic anemia
Copper deficiency is one of the causes of sideroblastic anemia that should be considered when evaluating this condition, particularly when the anemia is unresponsive to iron therapy alone. This anemia appears to be caused by defective iron mobilization due to decreased ceruloplasmin activity.

C

Arthritis
The use of copper bracelets in the treatment of arthritis has a long history of traditional use, with many anecdotal reports of effectiveness. There are research reports suggesting that copper salicylate may reduce arthritis symptoms more effectively than either copper or aspirin alone. Injections of superoxide dismutase (SOD), an enzyme containing copper (or manganese and zinc) that is found within the cells, has been used to treat arthritis patients in a Danish study. Relief from joint swelling, pain, and morning stiffness was reported. SOD is available in tablets in the United States but it may not be stable when taken by mouth. It remains unclear if this is an effective therapy. Further study is needed before a recommendation can be made.

C

Heart disease prevention
Low chronic copper intake has been suggested as a risk factor for heart disease, although it is not clear if increased copper intake is protective (15).

C

Cancer
Preliminary research reports that lowering copper levels theoretically may arrest the progression of cancer by inhibiting blood vessel growth (angiogenesis). Copper intake has not been identified as a risk factor for the development or progression of cancer.

C

Menkes' kinky-hair disease
Menkes' kinky-hair disease is a rare disorder of copper transport/absorption. The Menkes' gene codes for a P-type ATPase that has a mutation that prevents copper absorption in the intestine. Copper supplementation may be helpful in this disease, although further research is necessary before a clear management recommendation can be made.

C

Osteoporosis / osteopenia
Osteopenia and other abnormalities of bone development related to copper deficiency may occur in copper-deficient low-birth weight infants and young children. The copper-dependent enzyme , lysyl oxidase, is required for the maturation (cross-linking) of collagen, a key element in the organic matrix of bone. Osteoporosis has been observed in infants and adults with severe copper deficiency, but it is not clear whether marginal copper deficiency contributes to osteoporosis, or if copper supplementation is beneficial for the prevention/treatment of osteoporosis in individuals who are not copper deficient. Initial animal research reports that supplementation with copper may be helpful in the treatment and/or prevention of osteoporosis (16;17;17), although early human evidence is conflicting, with some positive results (18;19;20;21) and some negative results (21). The effects of copper deficiency or copper supplementation on bone metabolism and age-related osteoporosis require further research before clear conclusions can be drawn.

C

Cardiovascular disease prevention / atherosclerosis
The effects of copper intake or blood copper levels on cholesterol, atherosclerosis (cholesterol plaques in arteries), or coronary artery disease remain unclear. Studies in humans have produced inconsistent results, and their interpretation is hindered by the lack of a reliable marker of copper nutritional status. Although severe copper deficiency may cause heart damage (cardiomyopathy) through other mechanisms (22;23), as can copper disorders such as Wilson's disease, these conditions are different from heart disease due to atherosclerosis. Laboratory studies : Several studies report that outside the body, free copper is a pro-oxidant which oxidizes low density lipoprotein ( LDL ; "bad cholesterol") (3;8;24;7;25;26;27;28;29;30;31) as does the copper-containing protein ceruloplasmin (32;33). This has led some scientists to suggest that copper intake may increase the risk of building up atherosclerosis (cholesterol plaques in arteries). However, there is little evidence that copper or ceruloplasmin promotes LDL oxidation inside the human body. Some laboratory research suggests that copper may not cause LDL oxidation (34;35). Furthermore, the cuproenzymes superoxide dismutase and ceruloplasmin may possess antioxidant properties, leading some experts to propose that copper deficiency rather than excess may increase the risk of cardiovascular disease (36;37). Human population studies: Several epidemiologic studies have found that people with relatively higher blood copper levels are at greater risk of developing cardiovascular disease (38). However, it is not clear if the elevated levels are causes of disease, or simply markers in the body of some other process that is occurring (without being a cause). In fact, serum copper level largely reflects serum ceruloplasmin, and is not a sensitive indicator of copper nutritional status. More than 90% of serum copper is carried in ceruloplasmin. Serum ceruloplasmin levels can increase by 50% or more during physical stress (trauma, inflammation, disease). There are conflicting results from an autopsy study which found copper levels in heart muscle to be lower in patients who died of heart disease compared to than those who died of other causes (39;40;41). Cholesterol levels: The effect of copper intake on cholesterol levels remains unclear. Some research reports increased blood total cholesterol/LDL and decreased high-density lipoprotein ( HDL ; "bad" cholesterol) after copper supplementation (42), while other studies have found no correlation (36;37) or even decreased lipid levels. Additional research is necessary in this area before a clear conclusion can be drawn.

C

Immune system function
Copper is involved in the development of immune cells and immune function in the body (43;9). Severe copper deficiency appears to have adverse effects on immune function, although the exact mechanism is not clear. For example, low levels of white blood cells may occur (neutropenia), or diminished immune cell function. However, it is not clear if marginal copper insufficiency affects the immune system, or if copper supplementation is beneficial in individuals with normal baseline copper levels.

C

Schizophrenia
Some studies of schizophrenic patients report high blood copper levels with low urinary copper (suggesting that copper is being retained), and low blood zinc levels. In some of these cases, zinc was observed to be helpful as an anti-anxiety agent. The role of copper supplementation is not clear.

C

Age-related macular degeneration
There is not enough scientific evidence available to determine if copper plays a role in this disorder (44).

C

Marasmus
Copper deficiency may occur in this condition, and supplementation with copper may play a role in the nutritional treatment of infants with this condition (45). Infants with marasmus should be managed by a qualified healthcare professional.

C

Childhood growth promotion
Severe copper deficiency may retard growth. Adequate intake of micronutrients including copper and other vitamins may promote growth as measured by length gains. Copper is a part of the U.S. RDA (recommended daily allowance: 890 mcg for adolescents 14-18 years old; 700 mcg for children 9-13 years old; 440 mcg for children 4-8 years old; 340 mcg for children 1-3 years old; 220 mcg for infants 7-12 months old; 200 mcg for infants 0-6 months old). It is not clear that amounts beyond these recommendations are beneficial, and in fact may be dangerous in high quantities.

C

Neural-tube defect prevention
The risk of neural-tube defects is decreased in women who take folic acid and multivitamins during the periconception period (46). Supplementation with trace-elements alone such as copper does not appear to prevent these defects.

D

* Key to grades
A:
Strong scientific evidence for this use;
B:
Good scientific evidence for this use;
C:
Unclear scientific evidence for this use;
D:
Fair scientific evidence against this use (it may not work);
F:
Strong scientific evidence against this use (it likely does not work).

Uses based on tradition or theory
The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Allergies (), anemia, antibacterial, antioxidant, athletic performance, blood cell development, bone growth, bronchitis (), cancer, cataract prevention, decreasing cadmium absorption (;;), depression, ethambutol-induced optic neuropathy, fatigue, fetal development, hyperactivity (), infertility, learning disabilities, Hodgkin's disease biomarker (), muscle cramps (), oral deodorant (;), infection, phenylketonuria, plaque, pneumonia (), premenstrual syndrome, pyrrolizidine alkaloid toxicosis (;;), psoriasis (), rheumatic heart disease (), senility, stomach ulcer, aflatoxin toxicity (), vitiligo, weight gain, wound healing.

Dosing

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Standardization:

A variety of indicators were used to establish the U.S. recommended dietary allowance (RDA) for copper, including plasma copper concentration, serum ceruloplasmin activity, superoxide dismutase activity in red blood cells, and platelet copper concentration. The RDA for copper reflects the results of depletion-repletion studies and is based on the prevention of deficiency.

Adults (18 years and older):

U.S. Recommended Daily Allowance (RDA) for adults : 900 mcg for adults; 1000 mcg for pregnant women; 1300 mcg for nursing women; 890 mcg for adolescents 14-18 years old. Surveys suggest that most Americans consume less than the RDA for copper each day. Up to 3000-5000 mcg daily appears to be safe for consumption in children, and up to 10,000 mcg in adults. Vegan diets appear to provide adequate amounts of copper.

Copper deficiency : Copper deficiency may occur in individuals with malabsorption syndromes (including celiac disease, sprue, or short bowel syndrome), cystic fibrosis, in the elderly (6), or those receiving intravenous total parenteral nutrition (TPN) or other restrictive diets. Such individuals may require supplementation with copper (and other trace elements). Cases of known/suspected copper deficiency should be evaluated and managed by a physician and nutritionist.

Sources of copper : Copper occurs naturally in many foods, including vegetables, legumes, nuts, grains and fruits, as well as shellfish, avocado, and beef (organs such as liver). Because copper is found in the earth's crust, most of the world's surface water and ground water used for drinking purposes contains small amounts of copper. Water obtained from copper pipes contains copper.

Children (younger than 18 years):

U.S. Recommended Daily Allowance (RDA) for children : 890 mcg for adolescents 14-18 years old; 700 mcg for children 9-13 years old; 440 mcg for children 4-8 years old; 340 mcg for children 1-3 years old; 220 mcg for infants 7-12 months old; and 200 mcg for infants 0-6 months old.

Copper deficiency : Copper deficiency may occur in infants fed only cow-milk formulas (which are relatively low in copper content) or synthetic low lactose diets, premature/low-birth weight infants, infants with prolonged diarrhea or malnutrition, malabsorption syndromes (including celiac disease, sprue, or short bowel syndrome), cystic fibrosis, or during intravenous total parenteral nutrition (TPN) or other restrictive diets. Such situations may merit copper supplementation (and other trace elements), which should be under the supervision of a healthcare professional. In the United States, copper is not available in infant supplements.

Marasmus : management of marasmus should be under the supervision of a healthcare professional. 20-80 mcg/kg/day of copper sulfate supplementation has been reported as safe (45;59). No adverse effects on copper serum concentrations or ceruloplasmin were found in a controlled trial of 105 infants receiving parenteral nutrition with copper supplementation (60).

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

Insufficient evidence.

Side Effects and Warnings

Toxicity : Copper toxicity is rare in the general population. Excess copper consumption may lead to liver, kidney, or neurologic damage. Up to 3000-5000 mcg daily appears to be safe for consumption in children older than 3 years, and up to 10,000 mcg in adults. Excess dosing may lead to toxic symptoms including weakness, abdominal pain, nausea, vomiting, and diarrhea, with more serious signs of acute toxicity including liver damage, kidney failure, pleural damage, coma, and death (which can occur with ingestion of doses in the range of 1 gram of copper sulfate) (1;2;3;4;53;54;61). Other medical problems associated with copper toxicity in studies or anecdotally include anxiety, depression, fatigue, learning disabilities, memory lapses, diminished concentration, insomnia, seizure, delirium, stuttering, hyperactivity, arthralgias, myalgias, hypertension, gingivitis, dermatitis, discoloration of skin/hair, preeclampsia, postpartum psychosis, weight gain, or transaminitis. Acute copper poisoning has occurred through the contamination of beverages by storage in copper containing containers as well as from contaminated water supplies (62). In the U.S., the health-based guideline for a maximum water copper concentration of 1.3 mg/liter has been enforced by the Environmental Protection Agency (63). Liver damage may result from long-term exposure to lower doses of copper. The U.S. Food and Nutrition Board (FNB) has set the tolerable upper level of intake (ul) for copper at 10 mg/day from food and supplements.

Genetic disorders affecting copper metabolism such as Wilson's disease, Indian childhood cirrhosis, or idiopathic copper toxicosis place individuals at risk of adverse effects of chronic copper toxicity at significantly lower intake levels (5). Trientine is a copper-chelating agent used in the management of Wilson's disease. Penicillamine has also been used to bind copper and enhance its elimination in Wilson's disease. Zinc in therapeutic dosages has been used to inhibit copper absorption in patients with Wilson's disease. Animal research suggests that supplementation with taurine may reduce toxic effects of copper when given in combination, although it is not clear if this is the case in humans (61).

Copper-T devices are a type of intrauterine devices (IUD) used for birth control which have been linked to the development of anemia and increased risk of pelvic infection in some users (64;65;66;67).

Pregnancy and Breastfeeding

Pregnancy : The U.S. Recommended Daily Allowance (RDA) is 1000 mcg for pregnant women (68). It is unclear if copper supplementation is necessary during pregnancy to maintain adequate levels (69;52). Copper is potentially unsafe when used orally in higher doses. Animal studies suggest that trace metal aberrations, including copper, may be related to disturbed fetal growth or teratogenicity, particularly in the setting of diabetic pregnancy (68;70;71).

Lactation : The U.S. Recommended Daily Allowance (RDA) is 1300 mcg for nursing women (68). Copper is potentially unsafe when used orally in higher doses. Copper is present in breast milk (72).

References

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May 01, 2004

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