Chronic Copper Toxicity: an increasing Problem?

 Because of the low levels in Manitoba feedstuffs and the possible occurrence of copper-binding minerals (e.g. molybdenum), copper is routinely supplemented to prepared rations, supplements and/or mineral mixes destined to the cattle industry. Rations are formulated to exceed the minimum Cu requirement of 10 mg/kg (ppm) and usually contain 15-25 mg/kg. However, rations are occasionally seen which contain 40-50 mg/kg Cu with no justification - levels well in excess of what is necessary. When cattle consume excessive copper, large amounts of the mineral can be stored in the liver before toxicosis becomes evident. A sudden release of large amounts of copper from the liver to the blood can lead to hemolysis, jaundice and death.

In the past, NRC has set the maximum tolerable level of copper at 100 mg/kg. However, recent studies (1993, 1999) have shown that chronic copper toxicity can occur at the 40-50 mg/kg. These results are further supported by a research paper published in the October, 2001 issue of Journal of Dairy Science. The North Carolina State University (NCSU) study compared the effects of three treatments over a 61-day feeding period:
  1. Control (no supplemental Cu)
  2. 10 mg of Cu/kg of DM from copper sulfate
  3. 40 mg of Cu from copper sulfate
Copper status was evaluated using plasma Cu, liver Cu and serum cholesterol concentrations. The best indicator of Cu status is liver Cu content. Copper is stored in the liver and liver biopsies give an excellent assessment of copper status in the animal. Liver Cu levels less than 20mg/kg (dry weight) is indicative of a copper deficiency while levels above 500 ppm suggest a toxic situation. Plasma Cu content is often measured because of its simplicity but is a poor evaluator of Cu status in the liver. Plasma Cu content is maintained in the "normal" range unless copper levels in the liver are extremely low or extremely high. A research study in 1993 indicated cows considered to be deficient on the basis of serum Cu concentrations were actually near a toxic state based on liver biopsy specimens.
 
The effects of the three treatments on plasma Cu, liver Cu and serum cholesterol levels are shown below.
Initial liver Cu concentrations were similar for the three treatments. However, by the end of 61 days cows receiving 40 mg of Cu/kg of DM had liver concentrations indicative of Cu toxicity but no clinical signs of Cu toxicity were observed. Other research shows that the liver Cu levels and manifestation of Cu toxicity may be related to both the dose and duration of Cu administration. It is speculated that cows in this study may have shown clinical signs of toxicity if Cu supplementation was maintained for a longer period.
The 8.9 mg/kg present in the control diet was believed to provide adequate amounts of Cu as both liver and plasma Cu concentrations remained above concentrations considered to be indicative of Cu deficiency (liver <20 mg of Cu/kg of DM and plasma <0.6 mg of Cu/L).
 
Dry matter intake, average daily milk production, and milk fat, protein and somatic cell counts were similar across treatments.
 
Some breeds are known to be more susceptible to copper toxicity. In past research, Jersey cattle fed the same diet as Holstein cattle accumulated more copper in their livers. This data cautions that Jersey cows may be more prone to copper toxicity than Holstein cows.
The NCSU study also looked at the effects of dietary Cu on lipid (fat) metabolism and the fatty acid composition of milk. Milk fat has been criticized because it contains a less desirable balance of fatty acids than vegetable fat or fish oil (Bulletin of the International Dairy Federation, 2001). Milk fat has a large concentration of short chain fatty acids (C4 - C16) and relatively low concentrations of monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids. A higher proportion of long chain fatty acids (C18) and unsaturated fatty acids are desirable for human health. However, an increasing degree of unsaturation increases the likelihood of oxidized milk. Rations with over 35-40 mg copper/kg have long been associated with increased incidence of oxidized flavours in milk. The effects of dietary copper on milk fatty acid composition are shown below.

FA (% by wt)
Added Cu (mg/kg DM)

SE
0
10
40
C12:0
4.11
3.58
5.19
0.45
C 18:0
12.96
12.31
11.65
0.69
Saturated:Unsaturated
2.21
2.24
2.37
0.10
MUFA
25.26
24.61
23.84
0.79
PUFA
3.63
3.70
3.05
0.16

Cows receiving 40 mg Cu/kg had a statistically higher amount of C12:0 and a numerically greater amount of all short chain fatty acids (C12-C16) than cows fed either the control or the 10 mg/kg. The amount of unsaturated fatty acids in the milk was reduced at the higher level of copper intake. The mechanism by which Cu affects the profile of fatty acids is not clear but may involve changes in the rumen microbial population in the rumen.
The Nutrient Requirements of Dairy Cattle (2001) recommends the maximum tolerable dietary copper level should be reduced to 40 mg/kg unless dietary molybdenum is greatly elevated. An adjustment of the copper requirement based on breed is not warranted at this time.

References:
  1. Nutrient Requirements of Dairy Cattle. 7th rev. ed. 2001. National Research Council.
  2. Kennelly, John. 2001. The fatty acid composition of milk fat as influenced by feeding oilseeds. Bulletin of the International Dairy Federation no.366.
  3. Engle, Fellner and Spears. 2001. Copper status, serum cholesterol, and milk fatty acid profile in holstein cows fed varying concentrations of copper. J. Dairy Sci. 84:2308-2313.

Nutrition Update Volume 12 No.3, February 2002