Copper for Animals

Copper is required for the activity of enzymes associated with iron metabolism, elastin and collagen formation, melanin production, and the integrity of the central nervous system. It is required for normal red blood cell formation by allowing iron absorption from the small intestine and release of iron in the tissue into the blood plasma. Ceruloplasmin is the copper-containing transport protein. Copper is required for bone formation by promoting structural integrity of bone collagen and for normal elastin formation in the cardiovascular system. Copper is required for normal myelination of brain cells and spinal cord as a component of the enzyme cytochrome oxidase which is essential for myelin formation. Maximum immune response is also dependent on copper as indicated by depressed titers in deficient animals.

The process of normal hair and wool pigmentation requires copper. It is believed that copper is a component of polyphenyl oxidase which catalyzes the conversion of tyrosine to melanin and for the incorporation of disulfide groups into keratin in wool and hair (215).

A minimum requirement for copper cannot be given with great accuracy, since copper absorption and utilization in the animal can be markedly affected by several mineral elements and other dietary factors. Zinc, iron, molybdenum, inorganic sulfate and other nutrients can reduce copper absorption. For example, it has been known that molybdenum can depress copper absorption in grazing ruminants. However, only recently have we understood the role of sulfur in intensifying the interaction of molybdenum and copper. Sulfur has its affect by forming thiomolybdates in the rumen (160). In 1991, Spears (161) described the following reactions involved in the formation of thiomolybdates which inhibit copper metabolism.

Thiomolybdates bind with copper in the rumen to form insoluble complexes which are poorly absorbed. However, some thiomolybdates are absorbed and affect copper metabolism in the body (160). It has been discovered that thiomolybdates cause copper to be bound to blood albumins which renders the copper unavailable for any biochemical reaction in the body. Price (162) reported that the tri- and tetrathiomolybdates were the sulfur-molybdenum complexes responsible for reducing copper absorption while the di- and trithiomolybdates had the greatest effect on copper metabolism in the body. These data show how important it is, when evaluating the copper intakes of ruminants, to consider the amount of molybdenum, and the amount of sulfur in the diet.

Likewise, copper availability changes with the forage specie and preservation technique (219). For example, fresh grass has the lowest availability and is further reduced by small increments of molybdenum and sulfur. In forages preserved as hay, the inhibitory effects of molybdenum are detectable, but less than that of sulfur. In silages, molybdenum has a small effect but sulfur reduces copper availability in a logarithmic manner. Estimated copper availability for grazed forage, silage and hay were 1.4, 4.9 and 7.3%, respectively, in Scottish Balckface ewes when molybdenum was less than 2.0 ppm. These variations in copper availability with preservation method are probably due to changes in the release rates in the rumen of copper and its antagonists.

When evaluating mineral interactions and their effect on copper, it is essential to consider not only the feed, but also minerals in the water. For example, Smart et al., (163) found that reducing the sulfate content of drinking water from 500 to 42 mg per liter increased copper availability. This effect is independent of molybdenum, and probably results from the formation of insoluble copper sulfide. Ivan (164) proposed that rumen protozoa were important to this reaction. It appears that the protozoa degrade sulfur amino acids to sulfide which then reacts with the copper to form an insoluble complex.

The milk of certain species such as cattle, sheep, goats, pigs, dogs and rats is quite low in copper. In dairy cows, the level of copper is generally below 0.1 ppm, although it may go as high as 0.2 ppm after calving. But, if the dam’s intake of copper is adequate, the newborn will have a substantial storage of copper in the liver. The liver is the main storage organ for copper. With most species, liver copper levels are higher in newborns than in adults. Copper in the milk cannot be increased beyond the normal range by adding extra copper to diets already adequate in copper.

Table 24 gives information on the copper requirements and levels that are apt to be toxic.

Class of Animal	Copper Requirement in Total Diet (ppm)	Toxic Level in Total Diet (ppm)
Swine	5-6	>250³
Poultry	6-8	250-800
Horses	9	Not known
Dairy Cattle	12-16	40
Beef Cattle	10 (4-15)	100³
Sheep	7-11	25³
Goats	10⁴	8-25⁴
Other Animals	0.4-7.3	Not known

⁴ Since information is not available with goats, the levels recommended for sheep are suggested.

Ruminants are most sensitive to copper toxicity, while most non-ruminant animals have a relatively high tolerance for copper, especially if the diet is adequate in zinc and iron.

A deficiency of copper leads to poor iron mobilization, abnormal hematopoiesis, keratinization and decreased synthesis of elastin, myelin and collagen. Leg weakness, various types and degrees of leg crookedness, and the incoordination of muscular action also result. A subclinical deficiency causes reduced blood serum copper and ceroplasmin, a microcytic, hypochromic anemia, aortic rupture and cardiac hypertrophy (87, 92). Recent research suggests that copper and other trace mineral may be critical during early embryonic development. Copper concentrations in the developing pig embryo are much higher than in the uterine edometrium or ovary from day 12 to 30 of gestation (360). These data are interpreted to suggest that the developing conceptus has an increased demand for copper such that the maternal system shunts copper to the developing embryo.

Some producers are using copper at levels of 125 to 250 ppm in the diet as an antimicrobial compound. No toxic effects have been reported when levels of 125 to 150 ppm copper are used in the diet. However, occasional toxic effects have been reported when 250 ppm copper is used. The harmful effects are probably due to a lack of zinc and iron. The addition of 130 ppm zinc and 150 ppm iron has prevented harmful effects when using 250 ppm copper in the diet. With the baby pig, however, a higher level of iron, 170 ppm, is needed to counteract 250 ppm copper in the diet (92). Diets high in calcium may reduce zinc availability, which in turn could reduce the level at which copper is toxic. The use of high levels of copper in the diet will decrease by about 20% the rate of microbial decomposition of pig manure in the lagoon (105). If the manure is to be used as fertilizer on the land, this would be an advantage.

The use of 250 ppm copper in the diet increases the liver level of copper to a much greater extent than 125 ppm in the diet. The liver copper level can be decreased, however, by restricting the use of 250 ppm for pigs up to 100 to 125 pounds or by using a sulfide in the diet (106). Based on present knowledge, the safest procedure would be to use copper at a level no higher than 125 to 150 ppm in the diet, since it gives about the same effect as 250 ppm (92).

The source of copper is critical to achieving the anti-microbial effect in swine. Recent research comparing copper sulfate with copper oxide showed no effects by feeding up to 500 ppm copper from copper oxide while the 125 to 550 ppm copper from copper sulfate was efficacious (166).

Feeding high levels of copper may have non-nutritional advantages in that it improved the odor characteristics of swine waste (270). The mechanism of action is believed to result from the antibiotic-like functions of copper in the intestinal tract of pigs. Lower concentrations of cupric citrate seem to be as effective as 225 ppm of cupric sulfate. The replacement of all sulfate trace minerals with non-sulfate sources may further improve the odor characteristics.

A copper deficiency causes a microcytic, hypochromic anemia. Bone weakness, deformities and depigmentation in New Hampshire chicks are also observed. Dissecting aneurysm of the aorta occurs in copper deficient chicks. A marked cardiac hypertrophy occurs in turkey poults. A copper deficiency in the laying hen results in anemia and the production of eggs that are abnormal in size and shape, and some eggs have wrinkled and rough shells (95, 141).

The requirement for copper set by the National Research Council (Table 13) is 6-8 ppm (141). There are some poultry scientists, however, who feel that a higher level is needed and prefer a level of 10 ppm in the diet (95). Duck diets should contain 6-8 ppm of copper (300).

Very little information is available for copper needs of horses. A recent Cornell study indicates the copper requirement for the maintenance of mature ponies is about 3.5 ppm in the diet (107). A Minnesota study indicated that ponies were very resistant to chronic copper toxicity and could tolerate as high as 791 ppm in the diet (108). One horse study reported an apparent relationship between low blood serum copper levels and hemorrhaging in aged parturient mares. Another report indicated a copper deficiency caused bone abnormalities in the foal in Australia (154).

Copper is also required in the young horse to prevent Developmental Orthopedic Disease (DOD). Because this disease causes serious problems in the growing horse, most creep feeds are supplemented with 50 ppm copper and most weanling feed with 25 ppm (298).

Source of copper can have a huge impact on bioavailability in horses. Lawrence (2005) reviewed the literature describing apparent and true digestibility of copper sources in different horse diets. Apparent digestibility of copper varied from 9 to 48% and estimated true digestibility varied from 24 to 59%, respectfully (303). Copper concentrations in these diets varied from 7 to 52 ppm.

A deficiency of copper can result in reduced growth or weight loss, unthriftiness, decreased milk production, diarrhea, changes in hair coat color and texture, bone weakness and fractures, "pacing gait" in older cattle, reduced reproduction, difficult calving, retained placenta, birth of calves with congenital rickets and "falling disease" which is sudden death due to acute heart failure and anemia. Sometimes the black hair around the eye loses pigment and develops a gray-spectacled appearance (91, 156).

Copper nutrition can have a great impact on fertility in dairy cows. Suboptimal ovarian activity, delayed or depressed estrus, reduced conception rate and calving difficulty have been associated with copper deficiencies in dairy cattle (165).

Copper absorption is low in ruminants, usually only 1-10% of that reported for non-ruminants (337). More copper is required by cattle on pasture than when they are fed dry forage or concentrates. Copper in silage appears to be of intermediate availability compared to other forage sources.

Breed of dairy cow can have a dramatic effect on copper metabolism. Du (239) reported that Jerseys accumulated copper in their livers faster than Holsteins when given the same copper-rich diet ad libitum. Several reports from the field have suggested that Jersey and Guernsey cows are more susceptible to copper toxicity than Holsteins.

Copper deficiency symptoms include depraved appetite, stunted growth, suppressed immune system, rough hair coat, anemia, diarrhea, straight pasterns, depigmentation of the hair, and sudden death (falling disease). Reduced growth in cattle seems to be most dramatic when excess molybdenum causes the copper deficiency (240). In these cases liver and plasma copper concentrations may not reflect a copper deficiency. This has caused some to hypothesize that the excess molybdenum causes a “localized copper deficiency” within the body. Genglebach’s (241) research supports this concept in that neutrophils from heifers supplemented with molybdenum had lower copper zinc-superoxide dismutase activities than heifers that were made equally copper deficient using excess iron supplementation. Stress also affects how the cattle’s immune system responds to copper supplementation. In one study copper supplementation decreased antibody titers in unstressed calves, but increased the titers in stressed calves (265). Although copper is critical to a healthy immune system, there are other physiological barriers that can override copper status.

Copper requirement of beef cattle is 4 to 10 ppm in the total diet when the diet contains low levels of molybdenum and sulfate (157). In locations where diets contain high levels of molybdenum and sulfate, the level of copper required may increase threefold or more. Copper deficiency may occur when forages have a copper level below 5 ppm and the molybdenum level is above 3 to 5 ppm. In an Irish study 19% of 2612 cattle tested were deficient in copper despite wide spread copper supplementation (295).

Forages are more deficient in copper and higher in antagonist, such as sulfur, then commonly recognized (293). County extension agents collected 1021 forage samples from across the state of Tennessee. Copper was deficient or marginally deficient in 92.4% of the forage samples. Sulfur was considered at least marginally antagonistic to copper in 89.3% of the samples.

Breed also has a role in susceptibility to copper deficiency. Ward (242) reported that Simmental and Charolais cattle had a greater copper requirement than Angus. Differences in biliary secretion may explain the differences among breeds (243). Regardless of dietary treatment, biliary copper excretion was twice as high in Simmental compared to Angus cattle.

Several studies by Engle and Spears have shown the role of copper supplementation on carcass composition (266, 267, and 268, 269). Copper supplementation (10 mg/kg diet) has altered lipid metabolism and tended to increase plasma norepinephrine concentrations in feedlot cattle. This reduced back fat will improve the red meat yield per carcass and result in less waste. The increased polyunsaturated fatty acid concentration in muscle of copper-supplemented steers may result in a healthier product for human consumption.

Copper deficiency may occur in calves that are fed all milk diets for long periods of time or in cattle subsisting on forages produced in copper deficient soils or in soils that contain excess molybdenum (85, 157).

Curing or drying of forages may alter the chemical form of copper, making it more available than copper in fresh green plants (157). Plants that contain high levels of molybdenum, sulfur, phytate or lignin may reduce copper bioavailability (337).

Copper deficiency in suckling lambs results in a lack of muscular coordination, partial paralysis of the hindquarters, a swayback condition, degeneration of the myelin sheath of nerve fibers, and weak lambs at birth that may die because of their inability to nurse. Researchers have determined that the swayback condition results from vacuolation, chromatolysis, and necrosis of the large motor neurons in the brainstem nuclei and ventral horn of the spinal cord (305). Anemia, bone disorders and a lack of fertility also occur with a copper deficiency. Sheep produce "steely" or "stringy" wool, which is lacking in crimp, tensile strength, affinity for dyes, and elasticity. Black sheep show depigmentation of the wool (155).

Excess molybdenum in sheep diets causes a copper deficiency. Sheep start to scour a few days after grazing in a pasture with 5 to 20 ppm molybdenum. When the dietary copper level falls below normal, or if the sulfate level is high, molybdenum intakes as low as 1 or 2 ppm may prove toxic. Molybdenum toxicity is usually controlled by increasing the copper level in the diet by 5 ppm. But it is difficult to give the exact copper level needed because of the complexity of the copper-molybdenum-sulfur interrelationship and all the factors affecting it. Merino sheep may need 1 or 2 ppm more copper in the diet than other sheep breeds, probably due to their high level of wool production (93, 94, 96). The dietary amounts of copper that are adequate for some breeds of sheep are deficient for others, and possibly toxic to some (155).

Sheep are very intolerant of excess copper and toxicities have occurred in sheep with concentrations as low as 10 ppm (215). Growing swine are often fed copper concentrations as high as 250 ppm in the diet to improve performance. Cattle can consume diets containing 100 ppm copper without problem.

Copper toxicity in sheep usually results from the accumulation of copper in the liver over a period of a few weeks to more than a year with no clinical signs followed by a sudden release of liver copper stores to cause toxicity. In these situations, chronic copper poisoning may result from excessive copper intake or from low intakes of molybdenum, sulfur, zinc, or calcium or following liver damage (167). Sheep accumulate copper in the liver more readily than other farm animals, and over a period of time, 1,000 to 3,000 ppm on a dry weight basis may be achieved. During the accumulation phase, blood copper levels are normally in the range of 0.10 to 0.20 mg per deciliter. Toxicity results when stress conditions cause the liver cells to die and release the stored copper into the blood. Plasma copper levels then increase 10 to 20 fold. These elevated blood copper levels (500 to 2,000 mg/dl) usually precede clinical signs by 24 to 48 hours (167). The most common symptoms are anorexia, excessive thirst, and depression. These are accompanied by severe hemoglobinemia, anemia, icterus and methemoglobinemia. Most sheep will die within 1 to 2 days of the onset of these signs (168).

The ratio of copper to molybdenum is the most important dietary factor affecting copper toxicity in sheep. Ratios of 10:1 or less will prevent toxicity in most cases. The exact mechanism by which molybdenum prevents copper toxicity is poorly understood. However, it is known that an insoluble complex, CuMoO4, can be formed in the gastrointestinal tract, thus reducing copper absorption. This theory is substantiated by the fact that increasing dietary copper is an effective treatment for molybdenum toxicity.

Molybdenum concentrations in most feeds are in the range of 1 to 3 ppm. If molybdenum concentrations are less than 1 ppm, diets containing copper in the normal requirement range of 8 to 11 ppm have been known to produce toxicity (155). Sheep producers who live in or buy feed from molybdenum deficient areas should pay close attention to dietary copper levels. Such feeds as distillers dried grains and soybean meal, which are normally high in copper, should be limited in the diet. Importantly trace mineralized salt should be retained in the diet because it contains zinc which also reduces copper absorption. Diets containing high concentrations (100 ppm) of zinc have been shown to reduce liver copper stores. Eliminating trace mineral supplementation may actually worsen the situation by creating an even greater mineral imbalance.

Although prevention is much preferred, there are times when mass treatment is indicated. The most common treatment is to give a drench daily containing 50 to 100 mg of ammonium molybdate and 0.5 to 1.0g of sodium sulfate per animal for three weeks. To reduce labor, an aqueous solution of the two salts can be sprayed onto the feed. The Food and Drug Administration does not recognize molybdenum as safe for therapeutic purposes, so it can not be added to sheep diets as a preventative measure. Consequently, producers should consult a veterinarian with expertise in treating copper toxicity in these cases.

Besides nutrition, animal management factors can affect the incidence of copper toxicity in sheep. For example, although this disease can occur in both sexes of all breeds, mature ewes of British breeds seem to be the most susceptible. In the United States this disease is most common in the western states of the intermountain region. Although the disease can occur any time, peak incidence usually is in the fall and winter.

Environmental factors and stress can also affect the susceptibility of sheep to this disease. For example, grazing sheep in areas containing certain potentially toxic plants may predispose them to copper toxicity. Plants such as lupines, which contain toxic alkaloids, produce copper toxicity by impairing the liver’s ability to metabolize ingested copper. Chronic toxicity is also common in sheep grazing subterranean clover and is associated with normal levels of copper, low levels of molybdenum, and no apparent liver damage. The stress associated with shipping ewes from mountain ranges to pastures some distance away appears to make ewes more susceptible. Caution should also be exercised when feeding by product feeds known to contain high copper concentrations. For example, broiler litter which can be high in copper should not be fed to sheep (146).

Sheep producers should become familiar with copper and molybdenum status of feeds grown in their area. If the area is deficient in molybdenum or high in copper, feed samples should be analyzed routinely to monitor the copper:molybdenum ratio in the diet. Supplemental feeds which are known to be low in copper should be used whenever possible.

Goats appear to be more similar to cattle than sheep in their copper metabolism. For example, in research cited by Haenlein (335), the average copper concentration in the livers of goats was 10 ppm, while in sheep it averaged 196 ppm (fresh weight). These data are derived from animals from many sources on different diets, but it does suggest that goats do not store copper in their livers. A report by the European Commission entitled, “Opinion of the Scientific Committee for Animal Nutrition on the use of Copper in Feedingstuffs,” showed similar result. Sheep fed 7 ppm copper had 300 ppm (dry matter basis) copper concentrations in their livers, while goats fed similar copper levels had about one-third the copper at 100 ppm. Consequently, copper deficiency is much more common in goats than copper toxicity.

The potential signs of copper deficiency include diarrhea, poor weight gain, light hair coats, anemia and unthrifty appearance. California veterinary pathologist (336) reports the most common copper deficiency in goats they receive is weak kids, one to two months of age that are uncoordinated. The deficiency originates with the doe that is unable to transfer enough copper to the developing fetus. Copper deficiency in goats is usually determined by measuring the concentration in blood. Goats normally have 0.8 to 1.2 ppm copper in the serum. The exact copper requirement for goats has not been determined, but many producers with experience believe that it is 10-20 ppm. This assumes normal levels of molybdenum, iron, and sulfur, which can reduce copper absorption.

When sheep and goats are fed together, it is not uncommon to feed a low-copper mineral supplement designed for sheep. This increases the risk for developing copper deficiencies in kids born to does fed basal diets that are low in copper. Solaiman et al., (2005) fed Boer X Spanish goat kids a diet contain 14.5 ppm copper and then added 100 or 200 mg per head daily additional copper from copper sulfate (304). These data indicate that the 100 mg copper treatment improved gains, feed intake, and feed efficiency without adversely affecting health and well being of the goats. Practically, it is very unlikely that the same diet can be fed to sheep and goats without risking a copper toxicity in the sheep or a copper deficiency in the goats.

In summary, sheep and goats are dramatically different in their copper requirements. Based on these data it appears that copper requirements of goats must be re-evaluated and the NRC requirement adjusted accordingly (100).

With a few exceptions, studies on copper needs of other animals are quite limited. Based on the latest National Research Council publication on nutrient requirements of the other animals, the following are given as recommended levels or suggested requirements copper [(ppm)]: dog 2.9, cat 5, rat 5, mouse 4.5, rabbit 3, guinea pig 6, hamster 1.6, and gerbil 0.4 to 4.5 ppm in the total diet. When deficiency symptoms are given, they show some similarity to those of large animals. In all cases, copper is needed for the utilization of iron for the prevention of anemia. The range of copper needed is not much different from that for large animals (89, 102, 103, 142).