Nutritional Management

Nutritional Management

Nutritional Goals

Effective management of hepatobiliary disease requires both treatment of the underlying disease and nutritional support. Nutrient requirements of cats with liver disease are the same if not higher of those of normal animals, with those for protein and micronutrients even greater (Michel, 1995). The diet must be highly palatable and provide adequate energy, protein, fat, and all essential micronutrients. Care must be taken to avoid overwhelming the remaining metabolic capacities of the diseased liver. It is furthermore becoming increasingly evident that it is possible to modulate metabolic and pathological processes through the use of specific nutrients and metabolites (Remillard & Saker, 2005).

The aims of dietary management of feline liver disease are:
- To supply adequate energy and nutrients to fulfill basic energy requirements and prevent/correct malnutrition
- To limit further hepatocellular damage by reducing oxidative stress
- To support hepatocellular regeneration by providing limiting nutrients, especially protein
- To prevent or minimize metabolic complications such as HE.

Energy

Cats with liver disease are usually catabolic and have increased energy requirements.

Malnutrition is common in cats with hepatobiliary disease, due to decreased intake and the metabolic consequences of the disease (Figure 16). Negative protein and energy balance have a harmful influence on hepatocellular regeneration and repair, reduce immune response, alter intermediary metabolism, promote HE, and increase mortality (Biourge, 1997; Center, 1998). Correction and prevention of malnutrition are essential in management. Maintaining adequate nutritional intake is furthermore the only effective treatment in cats with hepatic lipidosis. Providing several small and palatable meals throughout the day will help to promote food intake and nitrogen balance. Cats that are anorexic for more than 3-5 days require tube feeding, whereas immediate tube feeding is usually recommended in cats with hepatic lipidosis. Force feeding and appetite stimulants are not recommended in cats in order to avoid learned food aversions (Remillard & Saker, 2005; Delaney, 2006).

Figure 16. Etiology of malnutrition in liver disease.

The diet should have a high palatability and energy density, since cats with liver disease usually have reduced appetites. An adequate supply of energy (50 - 60 kcal/kg/day) and protein is essential to prevent catabolism and malnutrition (Biourge, 2004; Remillard & Saker, 2005). The use of nonprotein calories is important to prevent the use of amino acids for energy and reduce the need for gluconeogenesis. In cats, nonprotein calories should mainly come from fat sources and include some highly digestible carbohydrates (e.g. rice).

Fat is a highly palatable and concentrated source of energy, and the diet’s caloric density is proportional to its fat content. Cats with liver disease can tolerate larger quantities of fat in the diet (30 - 50% of calories) than previously assumed. Fat restriction should only be considered in cats with severe cholestatic liver disease and suspected fat malabsorption, although adequate essential fatty acids must be provided. Incorporation of medium chain triglycerides in the diet is not recommended, since they may decrease palatability.

Altered carbohydrate metabolism in feline liver disease usually presents as a problem in maintaining euglycemia. Cats have a limited ability to digest, absorb and metabolize carbohydrates, and are often glucose intolerant in chronic liver disease. Carbohydrates should not represent more than 35% of the calories of the diet. Boiled white rice is useful because of its high digestibility, providing non-encephalopathogenic energy (Center, 1998). Complex carbohydrates such as soluble fiber can be useful in cats with cirrhosis and a tendency to hyperglycemia, because they smooth the postprandial glycemic response and prolong glucose delivery to the liver.

Protein

• Provision of adequate high-quality protein as well as calories is essential to ensure a positive protein balance and enable hepatic regeneration.
• Cats have high dietary protein requirements which are often increased in liver disease. Dietary protein should not be restricted unless there is clear evidence of hepatic encephalopathy and hyperammonemia.

Incorrect protein restriction in cats with liver disease causes further catabolism of endogenous proteins and loss of muscle mass, both of which increase the potential for HE. Feeding of excessive and/or poor quality protein should also be avoided since this may aggravate hepatic encephalopathy (Laflamme, 1999). The aim is to gradually increase the amount of protein in the diet, keeping the protein intake as close to normal as can be tolerated without precipitating signs of HE. As protein deficiency appears to be important in the pathogenesis of hepatic lipidosis, clinicians should provide patients the highest level of protein they will tolerate as soon as possible (Biourge, 1997). Protein digestibility and amino acid content are important. Although vegetable, soy or dairy proteins may be better tolerated than meat proteins in HE.

BCAA (branched chain amino acid) supplementation has been advocated in people with advanced liver disease and HE, since a decreased plasma ratio of BCAA to AAA (aromatic amino acids) has been considered an important pathogenic factor in its pathogenesis. The use of BCAA supplementation is expensive and controversial, and has not been investigated in cats.

Deficiencies of specific amino acids have furthermore been speculated to occur in feline liver disease, but study results have been conflicting and speculative. However, there is evidence that L-carnitine supplementation may protect cats against hepatic lipid accumulation and thus may be an useful dietary supplement for patients with liver disease (Ibrahim et al, 2003). A suggested dose is 250 - 300 mg/day. L-carnitine is a quaternary ammonium compound, and is an essential cofactor for the transport of long chain fatty acids into the mitochondria for subsequent oxidation and energy production (Remillard & Saker, 2005). It is normally synthesized in the liver from the amino acids lysine and methionine.

Fiber

Moderate quantities of dietary fiber can have several beneficial effects in liver disease. Soluble fiber is of benefit in managing HE. Colonic fermentation of soluble fiber (e.g. fructo-oligosaccharides) lowers the intraluminal pH and thus reduces the production and absorption of ammonia, the effects of which are similar to that of lactulose. Colonic fermentation also favors the growth of acidophilic bacteria (e.g. Lactobacillus spp.) that produce less ammonia and promote incorporation and excretion of ammonia in fecal bacteria.

Minerals

Potassium and zinc deficiencies are most frequent. Hypokalemia (Figure 17) is a common precipitating cause of HE in cats with liver disease (Center, 1998), and may be corrected by fluid therapy and dietary supplements. It usually occurs due to a combination of anorexia, vomiting or diarrhea, or excessive use of diuretics in the management of ascites. Zinc deficiency is related to reduced intake and is aggravated by the liver disease.

Zinc benefits the urea cycle and central nervous system neurotransmission, has hepatoprotective effects against a variety of hepatotoxic agents and has antioxidant functions (Feher et al, 1998, Marchesini et al, 1996). Zinc supplementation is furthermore useful to prevent hepatic copper accumulation in copper hepatotoxicosis, since zinc inhibits the absorption of copper from the gastrointestinal tract by causing induction of the intestinal copper-binding protein metallothionein. Dietary supplementation with zinc in cats with liver disease is done empirically, including zinc acetate (2 mg/kg per day), gluconate (3 mg/kg per day) or sulphate (2 mg/kg per day) divided into two or three daily doses. Zinc acetate is preferred because it is less irritating to the stomach; it should be given 1 - 2 hours before or after feeding. Serum zinc concentrations should be determined before and regularly after treatment is started in order to prevent iatrogenic zinc toxicity. Diets high in zinc (58 mg/1000 kcal) are furthermore useful for all patients with liver disease.

Figure 17. Head/neck ventroflexion in a cat with severe hypokalemia associated with hepatic lipidosis. A cat with feline hepatic lipidosis demonstrating severe head/neck ventroflexion (this is a very rare clinical sign). This cat had severe hypokalemia and hypophosphatemia; correction of the electrolyte imbalances resolved these clinical signs. (© SSharon Center (reprinted from Waltham Focus 14.2, 2004)

Zinc supplementation may reduce lipid peroxidation, has antifibrotic properties, prevents hepatic copper accumulation, and can reduce the severity of hepatic encephalopathy.

Vitamins

Vitamin deficiency is common in chronic feline liver disease. Water-soluble vitamins, especially B vitamins, which are essential for hepatic metabolism of nutrients; may be lost through vomiting or urinary losses or can become deficient as a result of anorexia, intestinal malabsorption, or decreased hepatic metabolism (Remillard & Saker, 2005). High daily B vitamin intakes are recommended for cats with chronic liver disease; this is safe since excesses are excreted in the urine. The diet should furthermore contain adequate levels of vitamin C in order to take advantage of its antioxidant properties.

Fat-soluble vitamins (vitamins A, D, E, and K) may become deficient in cholestatic liver disease, because their absorption depends on the availability of bile salts. Vitamin E is an important endogenous free radical scavenger that protects against oxidative injury. Supplementation (400 - 600 IU/day) is particularly indicated in cholestatic liver disease, but is likely also important in other forms of chronic liver disease. In severe cholestatic disease parenteral administration or an oral water-soluble form are preferred, since a certain level of enteric bile acids are required for its absorption.

Vitamin K deficiency is mostly relevant in cholestatic disorders, although it also may become depleted in severe chronic liver disease. Deficiency is documented by demonstration of prolonged coagulation times and normalization after parenteral administration of vitamin K1. Coagulopathies secondary to vitamin K deficiency should be treated with two or three doses of vitamin K1 (0.5 - 1.0mg/kg intramuscular or subcutaneously every 12 hours). The same dose can be given biweekly or monthly in chronic disorders in which continued repletion of vitamin K is required.

Antioxidants

Liver disease is associated with increased generation of free radicals (Figure 18). Supplementation with antioxidants such as vitamins E and C, as well as taurine, is essential in order to minimize oxidative injury. A combination of dietary antioxidants is better than a single one, since they act synergistically. A good balanced diet should also contain nutrients such as zinc, manganese and selenium, which are normally incorporated in enzymatic antioxidant systems.

Figure 18. Antioxidant action sites in the cell.  To view click on figure

SAMe is a nutraceutical that may be helpful in reducing hepatic oxidative injury. It is a precursor of glutathione, an important hepatic antioxidant enzyme that is often reduced in liver disease (Center et al, 2002). Oral supplementation helps to replenish hepatic glutathione stores and may thus improve antioxidant function. In addition, SAMe has anti-inflammatory properties. It is given as an enteric-coated tablet at 20 mg/kg/day. Side effects of the drug are rare.