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The Copper Conundrum

December 11, 2023 • Dr. Renee Streeter, DVM, DACVIM (Nutrition)

Copper is an essential mineral for dogs. A typical source of this nutrient in canine diets is the liver which can provide large amounts of copper. Ruminant livers (livers from cows, goats, and deer) are particularly high in copper compared to monogastric livers (like chicken or pork), but liver content can be variable even from an individual source. Supplemental copper in the form of cupric sulfate, cupric carbonate, cupric chloric, copper gluconate, and copper proteinates are also common. Previous research done in chicks as a representative model for dogs had shown that cupric oxide was virtually unabsorbable and is now no longer allowed as a copper source in dog food.1

Copper is part of enzymes involved in the production of blood cells, pigmentation, and control of neurotransmitters, as well as connective tissue integrity which is, in turn, involved in cardiovascular function and bone integrity. In addition, it is part of enzymes involved in oxidative metabolism and defense against free radicals. Signs of copper deficiency in dogs include hair depigmentation and hyperextension of the lower forelimbs. Excess dietary copper in dogs with normal metabolism typically results in interference with the absorption of zinc and iron, and it can also be stored in the liver. If it accumulates in excess, it can cause damage to hepatocytes (liver cells) resulting in elevated liver values on blood work and liver disease in dogs. This manifests as inappetence, vomiting, and, if severe, can result in hepatic failure. Some breeds of dogs, including Bedlington Terriers, Doberman Pinschers, Dalmatians, Labrador Retrievers, Cocker Spaniels, West Highland White Terriers, and Skye Terriers, are predisposed to a genetic disease that can result in copper-associated hepatotoxicosis (CAH)2 since there is an issue with copper excretion in the biliary system. Copper’s involvement in liver disease in other breeds is less clear. Abnormal copper concentrations in the liver can result from cholestatic liver disease3,4,5 or as a primary issue with excretion which results in hepatic injury. Breeds that are thought to have primary copper-associated hepatopathies include Skye Terriers, West Highland White Terriers, Doberman Pinschers, Dalmatians, and Labrador Retrievers. However, just because a dog is not known to be a breed with an increased risk for the development of this disease does not mean it cannot occur.

To diagnose copper hepatopathy in dogs, a liver biopsy is needed. Once the biopsy is obtained, the cells can be examined for patterns of damage and a stain can be applied to the sample to show copper accumulation in cells. This copper accumulation is quantified and, if a diagnosis of CAH can be made, treatment can begin.

Treatment for copper hepatopathy uses medications to help bind copper and prevent its absorption. In addition, a low copper diet where copper is about 1 mg/Mcal or 4 mg/kg dry matter (DM) is utilized. At this time there has been no research and no evidence to show that there is an amount of dietary copper that will result in hepatic copper accumulation in either dogs that are genetically predisposed or not predisposed. This is not to say that lower dietary copper cannot help to prevent copper accumulation in the liver, or that lower dietary copper is correlated to a decreased incidence of disease, it may, there is just no evidence to support those claims at this time.

A concern regarding a perceived increased incidence of copper-associated hepatopathy in dogs over the past 15-20 years has been raised. This is believed to coincide with copper oxide no longer being used as a dietary copper supplement for dogs and cats since it was disallowed in 1997.6 This is also believed to be exacerbated more recently by the popularity of high copper ingredients in diets such as liver and sweet potatoes.6 Copper concentrations of canine diets can be highly variable, averaging between 20-30 mg/kg DM, but may go as high as approximately 140 mg/kg DM.7 This is a concern because inflammation of the liver is seen more commonly with canine liver biopsies having more than 400 ug/g copper.6Interestingly the Association of American Feed Control Officials (AAFCO) minimum copper concentration for growth and reproduction was also increased from 7.3 mg/kg DM to 12.4 mg/kg DM in 2016. This was done to be consistent with the 2006 Nutritional Research Council (NRC) recommended allowance for peak lactation and it is slightly higher than the European Pet Food Industry Federation (FEDIAF) Guidelines and the NRC’s recommended allowance for growth. At the same time, the maximum copper concentration of 250 mg/kg DM was removed since the maximum copper concentration for dogs is not known.

This concern was brought to the attention of AAFCO and an expert panel was formed and met four times in 2021, to evaluate the request to lower the minimum dietary copper concentration and reinstitute a dietary copper maximum. Consideration of going back to only allowing copper oxide in the diet was opposed since this form is not absorbable. There was also some discussion about recommending only 25% of the supplemental copper in the diet come from chelated copper sources while the rest come from inorganic minerals since this was once a widely regarded rule of thumb that may have been lost to time and memory. At the time, the panel did not feel a footnote regarding this was needed but it was mentioned that this could be reconsidered at the request of the Pet Food Committee. The panel also rejected decreasing the recommended amount of copper to 3.6 mg/kg DM (0.9 mg/Mcal) since this is below the current minimum established by the NRC of dogs and cats and may result in a risk of causing signs of copper deficiency in the majority of the population. The task force also ultimately decided that, at this time, there is insufficient evidence to set a maximum copper concentration in dog foods, that setting a maximum would be an arbitrary decision not based on science, and that this decision would imply that those diets containing less than the maximum are safe while those that contain more are unsafe, none of which are currently known to be true.

At this point, given the continued concern raised at AAFCO meetings and veterinary conferences, a new AAFCO working group was organized to evaluate what might be considered a compromise until further research can be done to support either the lowered dietary copper minimum for dogs or a copper maximum. The compromise would allow for the use of a defined “controlled copper” voluntary claim which companies could use to indicate their copper concentration is below a certain defined concentration. At this point, the concentration that is proposed is 3.75 mg/Mcal or 15 mg/kg DM. This concentration was chosen because it allows for a reasonable margin above the minimum for adult maintenance and provides enough copper to support growth and reproduction. Companies choosing to utilize this claim would need to have copper listed on the guaranteed analysis so that consumers and veterinarians could readily ascertain the copper maximum helping them to make decisions on their pets and patients.

Concerns raised with this is that the 15 mg/kg DM is an arbitrary number still not known to reduce the incidence of copper-associated hepatopathy or the accumulation of hepatic copper. Those in favor of allowing the claim, however, believe this is a reasonable starting point that gives owners and veterinarians an idea of copper concentration if they do have a concern for their dog or their patient's risk of hepatic copper accumulation, which is especially important given the fact that sometimes copper concentrations in dog foods can go so high. In addition, it disallows companies wishing to make copper statements without a definition of what that copper claim entails. For instance, it would prevent a company from saying a diet containing a maximum of 40 mg/kg DM copper was a controlled copper diet when it is above the average copper content of diets on the market.

An additional concern raised around this topic is that owners may misconstrue this claim to mean diets which have this claim could be used to treat dogs with a diagnosis of copper hepatopathy, which would not be ideal. While this would indeed not be ideal, the designation or claim for “low copper” or similar designations, are not being used so that it can be reserved for those diets that are low enough in copper to help mitigate or treat the disease. Since these diets are below the current AAFCO minimum in copper concentration, these diets are prescription-only diets or are diets that are intended for supplemental feeding only. This “controlled copper” claim is only intended to provide knowledge of the copper content of the diet to those concerned about the potential and is not intended to mislead the public into thinking these diets are appropriate for the treatment of the disease. Indeed, other examples of this type of claim that are currently being used are weight loss/low-fat diets, over-the-counter low magnesium, and prescription urinary diets.

The viewpoint article that spearheaded this discussion6 references previous studies which show an increase in mean hepatic copper concentrations in dogs from <10 mg/kg DM in 1929, to 200 mg/kg in 1982, and 453 mg/kg in 1995. However, there are rumors that other, currently unpublished, data show that canine hepatic copper concentrations are decreasing over time. While it is difficult to reference or validate unpublished, rumored, data, most dogs in this country eat commercial diets with this wide variance in copper concentrations from various sources and most of them do not have CAH to our knowledge. In addition, some universities report that they do not notice an increase in canine hepatic copper concentrations.

Overall, more sound, prospective studies are needed on this topic and thankfully some work is being done currently. However, given the time-sensitive nature of this issue, it would be best to have a collaborative approach between the industry, veterinary internists, and veterinary nutritionists, as well as the FDA so time and money are not wasted on studies that the other parties will disagree with after the fact. What we need, (not just for copper, but also other minerals as well,) are safety studies that assess various breeds, healthy dogs, those with CAH, and those that have the genetic mutation predisposing to CAH when fed diets with known copper concentrations, in known amounts, from various sources. Since this will be something that will be expensive, labor intensive, and years in the making, what can we do in the meantime to work together to determine if this is truly an issue, and if so, how it can be mitigated in the interim?

References

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About the Author

Renee Streeter is a Doctor of Veterinary Medicine and a Diplomate of the American College of Veterinary Internal Medicine (Nutrition). She obtained her Bachelor's degree in Animal Science from Cornell University and served as a farm animal nutritionist for a major feed company before attending veterinary school at Ross University. Her clinical rotations were done at Cornell University’s college of veterinary medicine, where she stayed on to do her Clinical Nutrition residency. While working in a large general practice and doing clinical nutrition consultation, Dr. Streeter also founded her own veterinary nutrition consulting company and currently helps industry clients through her position as the Nutrition Practice Principal at BSM Partners.

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