Medical Uses of Copper in Antiquity

Copper Applications in Health & Environment

The first recorded medical use of copper is found in the Smith Papyrus, one of the oldest books known. The Papyrus is an Egyptian medical text, written between 2600 and 2200 B.C., which records the use of copper to sterilize chest wounds and to sterilize drinking water. Other early reports of copper's medicinal uses are found in the Ebers Papyrus, written around 1500 B.C. The Ebers Papyrus documents medicine practiced in ancient Egypt and in other cultures that flourished many centuries earlier. Copper compounds were recommended for headaches, "trembling of the limbs" (perhaps referring to epilepsy or St. Vitus' Dance), burn wounds, itching and certain growths in the neck, some of which were probably boils. Forms of copper used for the treatment of disease ranged from metallic copper splinters and shavings to various naturally occurring copper salts and oxides. A "green pigment" is spoken of which was probably the mineral, malachite, a form of copper carbonate. It could also have been chrysocolla, a copper silicate, or even copper chloride, which forms on copper exposed to seawater. In the first century A.D., Dioscorides, in his book De Materia Medica, described a method of making another green pigment known as verdigris by exposing metallic copper to the vapors of boiling vinegar. In this process, blue-green copper acetate forms on the copper surface. Verdigris and blue vitriol (copper sulfate) were used, among other things, in remedies for eye ailments such as bloodshot eyes, inflamed or "bleary" eyes, "fat in the eyes" (trachoma?), and cataracts.

In the Hippocratic Collection (named for, although not entirely written by, the Greek physician Hippocrates, 460 to 380 B.C.), copper is recommended for the treatment of leg ulcers associated with varicose veins. To prevent infection of fresh wounds, the Greeks sprinkled a dry powder composed of copper oxide and copper sulfate on the wound. Another antiseptic wound treatment at the time was a boiled mixture of honey and red copper oxide. The Greeks had easy access to copper since the metal was readily available on the island of Kypros (Cyprus) from which the Latin name for copper, cuprum, is derived.

By the time the Roman physician Aulus Cornelius Celsus began practicing medicine, during the reign of Tiberius (14 to 37 A.D.), copper and its derivatives had been firmly established as an important drug in the medical practitioner's pharmacopoeia. In Celsus' series, De Medicina, books one through six list many purposes for which copper was used together with the preparation and the form of copper most effective for each ailment. For the treatment of venereal disease, for example, Celsus prescribed a remedy consisting of pepper, myrrh, saffron, cooked antimony sulfide, and copper oxide. These were first pounded together in dry wine and when dry, once again pounded together in raisin wine and heated until dry. For a non-healing chronic ulcer, treatment consisted of copper oxide and other ingredients including enough rose oil to give a soft consistency.

Pliny (23 to 79 A.D.) described a number of remedies involving copper. Black copper oxide was given with honey to remove intestinal worms. Diluted and injected as drops into nostrils, it cleared the head and, when taken with honey or honey water, it purged the stomach. It was given for "eye roughness," "eye pain and mistiness," and ulceration of the mouth. It was blown into the ears to relieve ear problems.

In the New World the Aztecs also used copper for medical purposes. Don Francisco de Mendoza commissioned two learned Aztec Indian physicians to record the pharmacological treatments known by the Aztecs at the time of the Conquest. For the treatment of "Faucium Calor" (literally, heat of the throat, or, sore throat) they prescribed gargling with a mixture of ingredients containing copper.

Copper was also employed in ancient India and Persia to treat lung diseases. The tenth century book, Liber Fundamentorum Pharmacologiae describes the use of copper compounds for medicinal purposes in ancient Persia. Powdered malachite was sprinkled on boils, copper acetate as well as and copper oxide were used for diseases of the eye and for the elimination of "yellow bile." Nomadic Mongolian tribes treated and healed ulcers of venereal origin with orally administered copper sulfate.

Turning to more modern times, the first observation of copper's role in the immune system was published in 1867 when it was reported that, during the cholera epidemics in Paris of 1832, 1849 and 1852, copper workers were immune to the disease. More recently copper's role in the immune system has been supported by observations that individuals suffering from Menke's disease (an inherited disease in which there is defective copper absorption and metabolism) generally die of immune system-related phenomena and other infections. Further, animals deficient in copper have been shown to have increased susceptibility to bacterial pathogens such as Salmonella and Listeria. Evidence such as this has led researchers to suggest strongly that copper compounds not only cure disease but also aid in the prevention of disease.

In 1885, the French physician, Luton, reported on using copper acetate in his practice to treat arthritic patients. For external application he made a salve of hog's lard and 30% neutral copper acetate. For internal treatment, he used pills containing 10 mg. of copper acetate. In 1895, Kobert published his review of the pharmacological actions of copper compounds. Copper arsenate had been used to treat acute and chronic diarrhea as well as dysentery and cholera. A variety of inorganic copper preparations were found to be effective in treating chronic adenitis, eczema, impetigo, scorphulosis, tubercular infections, lupus, syphilis, anemias, chorea and facial neuralgia. An organic complex of copper developed by Bayer was shown to have curative powers in the treatment of tuberculosis. Copper treatment for tuberculosis continued until the 1940s, and various physicians reported on their success in using copper preparations in intravenous injections.

In 1939, the German physician, Werner Hangarter, noticed that Finnish copper miners were unaffected by arthritis as long as they worked in the mining industry. This was particularly striking since rheumatism was a widespread disease in Finland, and workers in other industries and other towns had more rheumatic diseases than did the copper miners. This observation led Finnish medical researchers plus the Germans, Hangarter and Lübke, to begin their now classic clinical trials using an aqueous mixture of copper chloride and sodium salicylate. They successfully treated patients suffering from rheumatic fever, rheumatoid arthritis, neck and back problems, as well as sciatica.

Until recently, just as in Pliny's time, the medical profession used copper sulfate as a means to clinically induce vomiting. This is based on the fact that one of the body's natural physiological responses to prevent copper intoxication is vomiting. A Manual of Pharmacology and its Applications to Therapeutics and Toxicology, published by W. B. Saunders Company in 1957 recommends the use of 0.5 gram of copper sulfate, dissolved in a glass of water, in a single dose, or three doses of 0.25 gram fifteen minutes apart, for this purpose.

Since 1934, it has been known that individuals suffering from such diseases as scarlet fever, diphtheria, tuberculosis, arthritis, malignant tumors and lymphogranulomas exhibit an elevation of copper in their blood plasma. Since then, the list of maladies bringing about such elevation has been extended to fever, wounds, ulcers, pain, seizures, cancers, carcinogenesis, diabetes, cerebrovascular and cardiovascular diseases, and irradiation and tissue stresses, including restricted blood flow. This suggests that this redistribution of copper in the body has a general role in responding to physiological, disease, or injury stress. On the other hand, the elevation of copper in the affected organ has led some to postulate that it was this excess of copper that caused the disease. Nonetheless, this elevation of copper in diseased states is suggested to account for the natural synthesis of copper-dependent regulatory proteins and enzymes in the body required for biochemical responses to stress. It may be that these natural copper complexes expedite the relief of stress and the repair of tissues. Thus, it appears that in addition to the anti-bacterial and anti-fungal activity of inorganic copper compounds as recognized by the ancients, metallo-organic complexes of copper have medicinal capabilities that are fundamental to the healing process itself.

Copper is known to be an essential element in human metabolism. However, copper does not exist in the body in measurable amounts in ionic form. All measurable amounts of copper in the body exist in tissues as complexes with the organic compounds of proteins and enzymes. Therefore, it has been concluded that copper becomes and remains intimately involved in body processes. Some copper complexes serve to store copper, others to transport it, and yet others play important roles in key cellular and metabolic processes. Studies into the roles that these copper complexes play and the mechanisms of these roles have further confirmed that copper enters into the prevention and control of a number of disease states in the body. As will be discussed below, the key to the effective use of copper-based pharmaceuticals is not the use of inorganic compounds of copper, as used by the ancients, but rather the use of metallo-organic complexes or chelates of copper. The process of chelating metals allows them to be smuggled in the transport process across the intestinal wall and thereby enter into the mainstream of nutrient flow and usage in the body.

The first modern research on the subject of copper medicinal substances was by Professor John R. J. Sorenson, of the University of Arkansas for Medical Sciences, College of Pharmacy, who, in 1966, demonstrated that copper complexes have therapeutic efficacy in the treatment of inflammatory diseases using doses that are nontoxic. Since then, copper metallo-organic complexes have been used to successfully treat patients with arthritic and other chronic degenerative diseases. More than 140 copper complexes of non-steroidal anti-inflammatory agents (aspirin and ibuprofen, for example) have been shown to be more active than their parent compounds. Copper aspirinate has been shown not only to be more effective in the treatment of rheumatoid arthritis than aspirin alone, but it has been shown to prevent or even cure the ulceration of the stomach often associated with aspirin therapy. Based on these experiences, the work of Professor Sorenson and other researchers around the world has progressed into the medicinal benefits of organic complexes of copper in a number of disease states. This work, thus far mainly based on animal research, has opened a whole new vista both into the understanding of copper's many-fold role in the body and in the practicality of using supplementary copper in the treatment of wound healing and inflammation-related disease states. Some of these potential indications are:

Ulcer and Wound-Healing Activities of Copper Complexes

It has been demonstrated that copper complexes such as copper aspirinate and copper tryptophanate, markedly increase healing rate of ulcers and wounds. For example, copper complexes heal gastric ulcers five days sooner than other reagents. Further, it has been shown that, whereas non-steroidal anti-inflammatory drugs, such as ibuprofen and enefenamic acid suppress wound healing, copper complexes of these drugs promote normal wound healing while at the same time retaining anti-inflammatory activity.

Anticonvulsant Activities of Copper Complexes

The brain contains more copper than any other organ of the body except the liver, where copper is stored for use elsewhere. This fact suggests that copper plays a role in brain functions. With reports of seizures in animals and humans following the protracted consumption of copper-deficient diets, it was reasoned that copper has a role to play in the prevention of seizures. It was subsequently discovered that organic compounds that are not themselves anti-convulsants exhibit anticonvulsant activity when complexed with copper. Further, it was found that copper complexes of all anti-epileptic drugs are more effective and less toxic than their parent drugs.

Anticancer Activities of Copper Complexes

As early as 1912, patients in Germany were treated for facial epithelioma with a mixture of copper chloride and lecithin. Success of such treatment suggested that copper compounds have anticancer activity. Work at the University of Liverpool in 1913 demonstrated that subcutaneous and intravenous injections of a copper salt or colloidal copper softened and degenerated carcinomas transplanted into mice. In 1930, work in France indicated that injections of colloidal copper mobilized and expelled tumor tissue. Recent work with mice in the USA has shown that, indeed, treatment of solid tumors with non-toxic doses of various organic complexes of copper markedly decreased tumor growth and metastasis and thus increased survival rate. These copper complexes did not kill cancer cells but caused them to revert to normal cells.

Anticarcinogenic Activity of Copper Complexes

Based on work in the treatment of cancers using copper complexes, researchers have found that these same complexes may prevent or retard the development of cancers in mice under conditions where cancers are expected to be induced.

Radiation Protection and Radiation Recovery of Copper Complexes

Ionizing radiation, such as that used in the treatment of cancer, has been shown to induce massive systemic inflammation. Ideally, such radiation-induced injury might be prevented or ameliorated by chemical repair mechanisms in the body. Thus, pharmacological approaches to the repair of radiation-damaged tissue are needed. As early as 1984, copper metallo-organic complexes have been shown to have radiation protection and radiation recovery activities. They are capable of causing rapid recovery of immunocompetence and recovery from radiation induced tissue changes. The mechanism of this activity appears to be tied to the ability of certain copper complexes to deactivate the superoxide, or "free," radicals liberated by ionizing radiation. In addition, since radiation has the capability of breaking the bonds of natural copper enzymes in the body, supplementing these with non-toxic doses of pharmaceutical copper complexes restores the lost tissue-repair capability. Since these complexes may also have anticarcinogenic activity, it is suggested that there would be merit in using copper complexes in the treatment of cancer and in particular, treating patients undergoing ionizing radiation therapy for their cancer, accidental exposure to radiation, and astronauts undertaking space travel.

Heart Disease and Copper Complexes

Numerous studies have drawn attention to the relationship between copper deficiency and heart disease. First observed in rats in 1936, this effect has now been traced to both a deficiency in copper and an imbalance in the copper-to-zinc ratio in the body. Work by Dr. L.M. Klevay at the U.S. Department of Agriculture, Human Nutrition Research Center in 1973 has led to the postulation that copper has a direct effect on the control of cholesterol. In continuing work published in 1975, he theorized that a metabolic imbalance between zinc and copper - with more emphasis on copper deficiency than zinc excess - is a major contributing factor to the etiology of coronary heart disease. Subsequent work by other investigators has shown that copper complexes also can have a valuable role in the minimization of damage to the aorta and heart muscle as oxygenated blood reperfuses into tissues following myocardial infarction. This action is based on the anti-inflammatory action of copper complexes. These and other studies suggest the use of copper dietary supplements as a means of preventing and controlling such diseases as atherosclerosis (a form of arteriosclerosis), coronary heart disease, aortic aneurysms and myocardial infarction. It has been speculated that the reason that the heart attack rate in France is lower than in the rest of Europe is because of the French practice of drinking red wine. Red wine has a higher copper content than white wine because it is prepared with the skin of the grape intact. The copper originates in the wine from the copper fungicides used on the grapes in the field. (See also Copper? You Bet Your Heart! )

Based on an abundance of historical data such as the foregoing, many researchers anticipate that copper will become an increasingly important component of tomorrow's medical treatments.

References:

1. The historical part of this paper is based on H.H.A. Dollwet and J.R.J. Sorenson, Historic uses of copper compounds in medicine, Trace Elements in Medicine, Vol. 2, No. 2, 1985, pp 80 - 87.

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