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Copper

Copper

Overview Dietary Sources Constituents/Composition Commercial Preparations Therapeutic Uses Dosage Ranges and Duration of Administration Side Effects/Toxicology Warnings/Contraindications/Precautions Interactions References Overview

Copper is an essential nutrient required for hemoglobin formation and many other functions. Copper is involved in producing and releasing energy through enzymes in the cytochrome system of cell respiration. It is essential for the development and maintenance of skeletal structures; specifically, copper helps to form collagen, especially in the bone and connective tissues. In the nervous system, copper conducts electrical impulses and helps maintain the myelin sheath around nerve fibers through the synthesis of phospholipids. In addition, copper has been linked to anti-inflammatory effects through oxygen-free radical metabolism and control of histamine levels. Copper is involved in iron metabolism and may play a role in thermal regulation, glucose metabolism, and blood clotting. Recent evidence suggests it also plays a role in proper functioning of the immune system.

The average daily intake by individuals consuming a typical Western diet has now been established as 1.0 to 1.5 mg of copper. This is lower than the 1.5 to 3.0 mg per day recommended to be safe and adequate. Pregnant women have higher needs, and greater supplementation may be indicated.

Copper deficiency in human beings is considered rare. Anemia resulting from copper deficiency has been found in individuals who have undergone intestinal bypass surgery, in patients receiving parenteral nutrition, in malnourished infants, and in persons ingesting excessive amounts of zinc. Copper deficiency in human beings has been linked to anemia, red blood cell rupture, demyelination and degeneration of the nervous system, pigmentation abnormalities in both skin and hair, abnormalities of the immune system, poor collagen integrity, faulty bone development, reduced activity of the antioxidant selenoglutathione peroxidase, elevated LDL cholesterol and reduced HDL cholesterol, and leukopenia (particularly granulocytopenia). Copper is important for converting T3 to T4, so low copper levels may reduce thyroid function. Animal studies indicate that copper deficiency results in central nervous system disturbances similar to Parkinson's disease, including symptoms of ataxia, tremors, and uncontrolled movements.

Wilson's disease, a genetic disorder, affects copper metabolism and leads to low serum and hair copper levels with high liver and brain copper levels. Serious problems, such as irreversible liver, kidney and brain damage, and even death, may result. It is treated with chelating agents; penicillamine is most often used as it binds copper in the gut and carries it out. Copper levels may be reduced through a low-copper diet, combined with more zinc and manganese in the diet and as supplements.

In Menkes disease, a rare problem of copper malabsorption in infants that can often be fatal, decreased intestinal absorption causes copper to accumulate in the intestinal lining.

Indian childhood cirrhosis, a hereditary disease with accumulating copper in the liver, used to be fatal, but can now be treated with chelators. The incidence of ICC in India has decreased in recent years, but similar diseases have appeared elsewhere.

Top Dietary Sources

Copper is found in many varied food sources. The best sources include:

  • Seafood (especially raw oysters; also squid, whelk, lobster, mussels, crab)
  • Organ meats (beef liver, kidneys, heart)
  • Nuts (e.g., cashews, filberts, macadamia nuts, pecans, almonds, pistachio nuts)
  • Legumes (especially lentils, navy beans, peanuts)
  • Chocolate (unsweetened or semisweet baker's chocolate, cocoa)
  • Cereals (e.g., bran flakes, shredded wheat, raisin bran)
  • Fruits and vegetables (e.g., dried fruits, mushrooms, tomatoes, potatoes, bananas, grapes, avocado)
  • Blackstrap molasses
  • Black pepper

An additional source is water that flows through copper piping.

Top Constituents/Composition

Copper is the third most abundant essential trace mineral. (Iron and zinc are first and second.) In biologic systems, copper is primarily found as Cu2+ although it can appear as Cu+ or even Cu3+.

Top Commercial Preparations

Copper is available combined with sulfate, picolinate, gluconate, and amino acids. Data is not available to evaluate one form against another.

Superoxide dismutase (SOD), with copper, has been used to treat arthritis. Stability in the stomach and small intestine is an issue, however, and oral use may be contraindicated. Enteric-coated tablets of active SOD may improve suitability for oral treatment of arthritis and other inflammatory disorders. In a Danish study, arthritis patients who were treated with injections of SOD obtained relief from many of their symptoms, such as joint swelling, pain, and morning stiffness.

Top Therapeutic Uses

Therapeutic uses for copper include:

  • Arthritis: Copper bracelets have been shown to reduce pain and inflammation associated with arthritis, although the exact mechanism is unknown. Recent research suggests that copper salicylate used to treat arthritis reduces symptoms more effectively than either copper or aspirin alone. SOD injections have reportedly provided relief in several European studies.
  • Leukopenia and anemia
  • Chemical hypersensitivity
  • Cardiovascular disease: to prevent aortic aneurysms, treat high cholesterol
  • Where copper levels are low, used to treat vitiligo, fatigue, allergies, and stomach ulcers

Top Dosage Ranges and Duration of Administration

  • Daily dietary copper intake recommended by the National Research Council of the United States: 1.5 to 3.0 mg per day for adults. For children 2 to 11 years, 1.5 to 2.5 mg. Not recommended for children under 2.
  • A zinc-to-copper ratio in the range of 8:1 to 15:1 is consistently recommended.
  • For leukopenia and anemia, daily doses up to 0.1 mg/kg of cupric sulfate orally, or 1 to 2 mg per day added to nutrient solution of nutrients for parenteral administration.

Top Side Effects/Toxicology

Copper toxicity is rare. Circumstances in which acute copper poisoning has occurred include accidental consumption by children, ingestion of several grams in suicide attempts, application of copper salts to burned skin, drinking water from contaminated water supplies, and consumption of acidic food or beverages stored in copper containers.

Toxicity results in nausea, vomiting, epigastric pain, headache, dizziness, weakness, diarrhea, and a characteristic metallic taste. In severe (but rare) cases, tachycardia, hypertension, jaundice, uremia, coma, or death can result.

Top Warnings/Contraindications/Precautions

Chronic copper toxicosis has been observed in dialysis patients following months of hemodialysis when copper tubing was used and in vineyard workers using copper compounds as pesticides.

Copper is an emetic. As little as 10 mg usually produces nausea, and 60 mg usually produces vomiting. The lethal dose for copper may be as little as 3.5 g. Copper supplements should be kept away from children.

Top Interactions Allopurinol

Allopurinol forms complexes with copper in vitro (Malkiel et al. 1993). The ability of the drug to chelate copper may impart the protective effects against cardiac damage in bypass patients.

Cimetidine

In young rats, intermediate to high doses of cimetidine (875 to 1750 mg/kg/day) administered intragastrically four times weekly for 5 weeks elevated hepatic and plasma copper concentrations, and caused mineral redistribution as well as pathological changes in some tissues (Naveh et al. 1987).

Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

Administration of copper aspirinate to arthritic rats for 20 days increased hepatic copper concentrations (Kishore 1990). However, copper complexes of NSAIDs exhibit more potent anti-inflammatory activity than NSAIDs alone (Miche et al. 1997). It is not known whether copper supplements enhance the anti-inflammatory activity of NSAIDs.

Oral Contraceptives

Oral contraceptives have been shown to increase the levels of copper in women (Dorea et al. 1982; Horwitt et al. 1975; Tyrer 1984).

Penicillamine

D-penicillamine chelates copper and inhibits accumulation of copper in cells (Klein et al. 2000).

Top References

Asseth J, Haugen M, et al. Rheumatoid arthritis and metal compounds—perspectives on the role of oxygen radical detoxification. Analyst. 1998;123:3-6.

Dorea JG, Ferraz E, Queiroz EF. [Effects of anovulatory steroids on serum levels of zinc and copper]. Arch Latinoam Nutr. 1982;32(1):101-110.

Ensminger AH, Ensminger ME, Konlande JE, Robson JRK. Foods and Nutrition Encyclopedia. 2nd ed. Vol. 1. Boca Raton, Fla: CRC Press Inc; 1994;1:476-479.

Garrison RH Jr, Somer E. The Nutrition Desk Reference. 3rd ed. New Canaan, Conn: Keats Publishing Inc; 1995:188-192.

Haas EM. Staying Healthy with Nutrition. Berkley, Calif: Celestial Arts Publishing; 1992:190-194.

Hardman JG, Gilman AG, Limbird LE, eds. Goodman and Gilman's Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill; 1996:1325-1326.

Heinerman J. Heinerman's Encyclopedia of Nature's Vitamins and Minerals. Paramus, NJ: Prentice Hall Inc; 1998:250-255.

Horwitt MK, Harvey CC, Dahm CH Jr. Relationship between levels of blood lipids, vitamins C, A, and E, serum copper compounds, and urinary excretions of tryptophan metabolites in women taking oral contraceptive therapy. Am J Clin Nutr. 1975;28(4):403-412.

Kishore V. Effects of copper aspirinate and aspirin on tissue copper, zinc, and iron concentrations following chronic oral treatment in the adjuvant arthritic rat. Biol Trace Elem Res. 1990;25:123-136.

Klein D, Lichtmannegger J, Heinzmann U, et al. Dissolution of copper-rich granules in hepatic lysomes by D-penicillamine prevents the development of fulminant hepatitis in Long-Evans cinnamon rats. J Hepatol. 2000 Feb; 32(2):193-201.

Malkiel S, Har el R, Schwalb H, et al. Interaction between allopurinol and copper: possible role in myocardial protection. Free Radic Res Commun. 1993; 18(1):7-15.

Mazzetti I, Grigolo B, Borzai RM, Meliconi R, Facchini A. Serum copper/zinc superoxide dismutase levels in patients with rheumatoid arthritis. J Clin Lab Res. 1996;26(4):245-249.

Miche H, Brumas V, Berthon G. Copper(II) interactions with nonsteroidal antiinflammatory agents. II. Anthranilic acid as a potential. OH-inactivating ligand. J Inorg Biochem. 1997 Oct;68(1):27-38.

Murray MT. Encyclopedia of Nutritional Supplements. Rocklin, Calif: Prima Publishing, 1996:199-203.

Naveh Y, Weis P, Chung HR, et al. Effect of cimetidine on tissue distribution of some trace elements and minerals in the rat. J Nutr. 1987;117:1576-1587.

Newstrom H. Nutrients Catalog. Jefferson, NC: McFarland & Co; 1993:141-151.

Olivares M, Uauy R. Copper as an essential nutrient. Am J Clin Nutr. 1996;63:791S-796S.

Pennington JA, Schoen SA. Total diet study: estimated dietary intakes of nutritional elements. Int J Vitam Nutr Res. 1996;66:350-362.

Shils ME, Olson JA, Shike M, Ross AC. Modern Nutrition in Health and Disease. 9th ed. Baltimore, Md: Williams & Wilkins; 1999:241-252.

Tyrer LB. Nutrition and the pill. J Reprod Med. 1984;29(7 Suppl):547-550.

Uauy R, Olivares M, Gonzalez M. Essentiality of copper in humans. Am J Clin Nutr. 1998;67(5 suppl):952S-959S.

Wapnir RA. Copper absorption and bioavailability. Am J Clin Nutri. May 1998;67;5:1054s.

Werbach MR. Nutritional Influences on Illness. 2nd ed. Tarzana, Calif: Third Line Press; 1993:655-680.

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