Nutritional Management of Copper Hepatopathy

Copper is an essential nutrient required in trace amounts.¹ It is a component of enzymes that play a role in many functions (e.g., bone and cartilage development, iron metabolism, hair color, connective tissue development).² Although complete and balanced commercial diets ensure copper deficiency and toxicity are rare in dogs, cases of copper-associated hepatopathy (CAH) can still occur due to excessive copper accumulation, which may be influenced by a variety of factors, including genetic mutations, dietary intake, and chronic hepatitis. This article will discuss copper deficiency, copper toxicity, nutritional considerations, nutritional management, and regulatory challenges.

Copper Deficiency

Although copper is needed, cases of deficiency are uncommon. In 1991, copper deficiency was evaluated in 5 growing puppies that were fed a copper-free diet after weaning.³ The first clinical signs occurred 3 months after feeding the copper-free diet and included loss of color in the pigmented hair around the face and head. After 4 months of eating the diet, hyperextension of the distal phalanges was noted in 4 of the dogs. After 6 months, hemoglobin and packed cell volume were lower in dogs fed the copper-free diet than those in the control group. In 2001, a case report described iatrogenic copper deficiency in a Bedlington terrier that was undergoing copper chelation.⁴

Copper Toxicity

Although onset of copper deficiency is slow, onset of severe copper toxicity is rapid in dogs fed very high doses. One dog given 165 mg/kg PO of copper sulfate experienced vomiting and death 4 hours after ingestion.⁵ As with copper deficiency, acute copper toxicity is uncommon; however, there is concern that the incidence of CAH has been increasing.⁶

CAH is a liver disease caused by excess accumulation of copper in the liver, which can result from increased dietary copper intake, defects in hepatic copper metabolism, or impaired ability to excrete copper through the biliary system.⁷ Excess copper accumulation in the liver can result in oxidative damage of the hepatocytes, which leads to inflammation and eventual cirrhosis.⁷ Copper accumulation in the liver can result from primary or secondary copper storage disorders.

Primary Copper Hepatopathy

Primary CAH is related to genetic mutations, including the COMMD1 mutation in Bedlington terriers and the ATP7B mutation in Labrador retrievers.¹ Although specific genes have not been identified in other breeds, a heritable cause is suspected for Doberman pinschers, West Highland white terriers, Dalmatians, and Skye terriers.¹ In dogs with primary disorders, copper accumulation is centrilobular with concentrations typically exceeding 1000 ppm (normal copper concentration is considered to be less than 400 ppm).

Secondary Copper Hepatopathy

In contrast, in dogs with secondary CAH, copper accumulation is periportal and is not linked to genetic mutations.⁷ Dogs with secondary CAH accumulate copper as a result of chronic hepatitis or chronic, high dietary intake of copper.⁶

Diagnosis of CAH is beyond the scope of this article. Information can be found at go.navc.com/404SJEk.

Nutritional Considerations for CAH

The potentially increased prevalence of copper hepatopathy in dogs has veterinarians considering how diet may play a role. Suggested contributing factors are AAFCO changes in regulations, including the requirement to use more bioavailable copper compounds and the removal of a maximum concentration.^6,8 Hepatic copper concentrations in dogs have been reported to be increasing over the past 15 to 20 years.^6,8 The dog’s minimum copper requirements can be calculated using the AAFCO adult maintenance minimum (1.83 mg/1000 kcal) and the dog’s estimated ideal weight.⁹ A study evaluating mineral content of 45 over-the-counter diets formulated for dogs determined that the median concentration of copper was 4.4 mg/1000 kcal (range, 2.3 to 9 mg/1000 kcal), and in none of the diets did copper fall below the AAFCO minimum requirement.¹⁰ The median concentration is approximately 2.4 times the minimum requirement for adult maintenance. The highest copper concentration found (9 mg/1000 kcal) was almost 5 times the minimum for adult maintenance.

Overweight/Obesity

Another factor to consider is that many dogs are overweight or obese due to excessive calorie intake. Along with consuming excess calories, these dogs are also ingesting excessive amounts of nutrients, including copper, as shown in the following example.

Imagine a 36-kg (80-lb) Labrador retriever with a body condition score of 9 out of 9 (approximately 40% overweight). If the dog is consuming 1600 calories of a diet with a copper concentration of 9 mg/1000 kcal, it would be consuming 14.4 mg of copper per day.

The dog’s actual copper needs are based on the AAFCO minimum requirement and its estimated ideal weight. Because the dog is 40% overweight (140% of ideal weight), to determine its ideal weight, you would divide its current weight by 140% (or 1.4). Thus, the dog’s ideal weight would be around 26 kg or 57 lb (36 kg/1.4). For a dog of this weight, resting energy requirement (RER) would be approximately 806 kcal per day. If the dog consumed the ideal calorie amount from a diet meeting the AAFCO minimum copper requirement, it would ingest only about 1.5 mg of copper per day, which is significantly less than its current intake of 14.4 mg of copper per day.

Nutrition Math 101: Important Calculations

Copper Chelators

In managing CAH, factors to consider are reducing the amount of dietary copper being consumed and enhancing the excretion of copper from the body. Copper chelators, such as penicillamine, are used to increase copper excretion.¹¹ Unfortunately, side effects of penicillamine (e.g, vomiting, nausea, hyporexia) are common. In the author’s experience, dogs with copper hepatopathy are often referred to the nutrition service due to gastrointestinal signs and lack of appetite. For some patients, formulating a home-prepared diet can address these signs; however, some dogs continue to experience chronic gastrointestinal issues, anorexia, and ongoing weight loss. Inappetence can occur during the late stages of chronic hepatitis; however, these signs can also be a side effect of penicillamine. Research in this area is ongoing, and investigators at the author’s institution are finding that a lower dose of penicillamine may still achieve the desired effect while reducing the side effects.

Nutritional Management for Patients With Copper Hepatopathy

Nutrients to Consider

Protein

Typically, dogs with copper-associated hepatitis will not have liver dysfunction until late-stage disease; therefore, protein restriction is not necessary unless they have signs of hepatic encephalopathy.¹¹ In fact, liver inflammation may result in increased need for protein.¹¹ A recommended diet provides at least 45 g of protein per 1000 kcal; however, some dogs may require more, and the protein level may need to adjusted based on the individual patient’s needs.¹¹

Zinc

Zinc plays a role in intestinal cell synthesis of metallothionein, which binds copper within the cell. When these cells slough during the normal cycle of cellular regeneration, the bound copper is excreted unabsorbed in the feces.¹² However, it can take several months for plasma zinc concentrations to reach therapeutic levels that will reduce copper absorption.¹² As a result, zinc is generally not considered a therapeutic option for managing CAH.¹¹

Antioxidants

Because of the oxidative damage that occurs with copper accumulation, diets for managing copper hepatopathy should contain antioxidants. Vitamin E is an essential nutrient that protects the cells from peroxidative damage from free radicals. Omega-3 polyunsaturated fatty acids (PUFAs) are often included in diets or provided as supplements due to their inflammation-modulating effects. However, when supplementing with additional fatty acids, it is recommended to increase the amount of vitamin E by 0.6 IU for every gram of PUFA in diets containing more than 83 g of PUFAs per kg of diet.⁹ Doing so is particularly relevant for dogs with CAH because they require additional antioxidants to counteract the oxidative damage caused by copper.

Control of Copper Intake

In the management of CAH, the primary goal is to reduce the amount of copper in the diet; however, this can be challenging because most commercial diets contain more copper than is recommended for dogs with CAH.

Water

A less common, but potentially variable, source of copper to consider is water. The copper concentration in drinking water can vary, but homes with copper pipes have been reported to have a higher concentration of copper.¹³ For people with Wilson disease, a copper-related disorder that is similar to CAH in dogs, whose homes have copper pipes, it is recommended to let approximately 500 mL of water run from the faucet before it is used for drinking.¹³ For dogs, the recommendation is to flush the line for 5 minutes to minimize the risk for additional sources of copper.

Diet

The dietary recommendation for patients with CAH is to feed a diet that contains < 1.2 mg/1000 kcal of copper.¹¹ Therapeutic diets formulated for dogs with liver disease are low in copper but also relatively low in protein, which can be challenging for dogs that need higher dietary protein levels. One option is to add a lean protein source (e.g., egg white, chicken breast, whey protein) to increase dietary protein while avoiding excess calories (TABLE 1). Any food added to a meal should not exceed 10% of the total daily caloric intake. One way to determine how much protein to add is to calculate the patient’s protein requirement by using the National Research Council (NRC)–recommended allowance for protein (3.28 × [body weight in kg]^0.75).² Then determine how much protein the dog is consuming from the diet and calculate the difference, which can be used to determine how much protein to supplement if desired.

For example, consider a 25-kg (55-lb) dog that is eating its RER (780 calories per day) of a diet that contains 40 g of protein per 1000 kcal of diet. The NRC-recommended protein allowance for this dog is 37 g per day, but the current diet only provides 31 g per day. To meet the dog’s protein requirement, 6 g of protein from a lean protein source can be added.

To prevent nutrient imbalances, treats or toppers should be limited to 10% of total daily caloric intake, which for the dog in this example is 78 calories per day. To provide the desired additional 6 g of protein to this patient, 20 g of cooked chicken breast could be given, which contains 32 calories, below the recommended 10% calorie limit for toppers (TABLE 1). Treats and foods high in copper should be avoided, including:

• Organ meat
• Beef liver
• Shellfish
• Dark leafy greens
• Mushrooms

Regulatory Challenges

In February 2021, AAFCO began reviewing concerns about the reportedly increased prevalence of CAH and the potential contributions of pet food to the condition. In August 2022, AAFCO released a final report from an expert panel stating that there was insufficient evidence linking CAH with the copper concentration in dog food.¹⁴ The discussions continued; in early 2024, AAFCO sought public input on a “controlled copper” claim, and in May 2024, the Pet Food Committee voted down the option of having a voluntary “controlled copper” claim.¹⁵ As a result, copper in dog food will continue to have only a minimum requirement without a maximum limit.

Only 3 currently available products meet the low-copper recommendations for dogs with CAH:

• Hill’s Prescription Diet l/d (hillspet.com)
• Royal Canin Hepatic (royalcanin.com)
• Just Food For Dogs Hepatic Support Low Fat (justfoodfordogs.com)

Some companies (e.g., Voyager Dog Food Co., voyagerdogfoodco.com) market their products as having no added copper. The reported copper range for these diets is 2 to 2.4 mg/1000 kcal, which is below the median concentration of 4.4 mg/1000 kcal found by Gagné et al and meets the AAFCO minimum requirement but still exceeds the recommended levels for dogs with CAH.¹⁰

Many factors can contribute to the copper concentration of pet food. It would be helpful for pet food manufacturers to monitor the copper concentration of the ingredients they are using, especially organ meat such as beef liver, as well as control the amount of mineral supplement that is being added to the food. In addition, final products should be analyzed for copper concentration throughout the year to monitor for seasonal or regional differences that could influence copper concentrations in dog food.

Summary

Copper is an essential trace mineral for dogs but must be consumed in appropriate amounts. Reports suggest that the prevalence of CAH is increasing. Management involves feeding low-copper diets and administering copper chelation therapy. However, chelation medication often has side effects, making prevention a more desirable approach than treatment. Although genetics play a role, the high bioavailability and concentration of dietary copper may also contribute to this condition; although genetics cannot be altered, the copper content in pet food can be controlled. Pet food companies should continue to closely monitor the copper concentrations in ingredients and finished products. Continued research should provide more information about contributing factors and effective preventive measures.