Adaptation of Nutritional Intakes

4. Adaptation of Nutritional Intakes

Diets for animals with liver disease are best formulated on an individual basis, with consideration given to the type and origin of the liver disease and the extent of liver dysfunction (Laflamme, 1999). Care must be taken to avoid overwhelming the remaining metabolic capacities of the diseased liver. The diet must be highly palatable and provide adequate energy, protein, fat, and all essential micronutrients. It is furthermore becoming increasingly evident that it is possible to modulate metabolic and pathological processes through the use of specific nutrients and metabolites.

Correction and prevention of malnutrition are essential in the management of dogs with liver disease. Impaired dietary intake, malabsorption associated with severe cholestasis or portal hypertension, and catabolism all contribute to protein-calorie malnutrition, resulting in loss of muscle mass and hypoalbuminemia. Negative protein and energy balance promote HE, reduce immune response and increase mortality (Center, 1998). Providing several small meals daily as well as a bedtime snack will improve nitrogen balance and carbohydrate availability. Tube feeding via a nasogastric, esophagostomy or gastrostomy tube may be required in dogs that are anorexic for more than 3 - 5 days.

The Aims of Dietary Management of Liver Disease Are:

(1) To supply adequate energy and nutrients to fulfill basic requirements and prevent malnutrition
(2) To limit further liver damage by preventing accumulation of copper and free radicals
(3) To support hepatocellular regeneration
(4) To prevent or minimize metabolic complications, such as hepatic encephalopathy and ascites

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

Provision of adequate high-quality proteins as well as calories is essential to ensure a positive protein balance and enable hepatic regeneration. Protein levels are often inappropriately restricted in dogs with liver disease in order to manage possible hyperammonemia. In fact, protein requirements are at least normal or even increased, and many dogs with liver disease do not have hyperammonemia.

Energy

An adequate supply of both energy and protein is essential to prevent weight loss. The use of non-protein calories is important to prevent the use of amino acids for energy and reduce the need for gluconeogenesis. The diet should have a high energy density, since dogs with liver disease usually have reduced appetites. Normal daily maintenance needs in the dog are 110 - 130 kcal ME/kg0.75 (Table 7) (Bauer, 1996).

Normally, energy is best supplied in the form of fat since it is a highly palatable and concentrated source of energy. The diet's caloric density is proportional to its fat content. Dogs with liver disease can tolerate larger quantities of fat in the diet (30 - 50% of calories) than previously assumed (Biourge, 1997).

Fat restriction should only be considered in the few cases with severe cholestatic liver disease and suspected fat malabsorption, although adequate essential fatty acids must be provided.

Altered carbohydrate metabolism in dogs with liver disease can induce either hyper- or hypoglycemia. Hypoglycemia may be seen in acute fulminant liver disease, whereas hyperglycemia is infrequently seen in dogs with cirrhosis. Carbohydrates should not represent more than 45% of dietary calories, especially in dogs with cirrhosis, which may be glucose intolerant. Boiled white rice, and to a lesser degree pasta, are useful because of their high digestibility. Soluble fibers are useful in dogs with cirrhosis and a tendency to hyperglycemia, because they smoothen the postprandial glycemic response and prolong glucose delivery to the liver (Center, 1998).

Protein

Dietary Protein Level

Incorrect protein restriction in dogs with liver disease causes 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 signs of HE. In dogs, protein should represent as a minimum 10 to 14% of dietary calories, preferably at least 20%, and most dogs can tolerate higher quantities (Biourge, 1997; 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 (Michel, 1995).

Protein Type

The quality and source of the protein are important. High-quality proteins are better digested (Figure 6) and have an amino acid content close to the animal's requirements. Proteins of animal origin used to be considered as having a higher quality than proteins of plant origin, but soy isolates, wheat gluten and dairy products are better tolerated than meat proteins in people with HE, and this is probably also the case in dogs (Strombeck et al., 1983). The potential benefit of vegetable proteins is attributed to their high fiber content, which causes a decrease in transit time and promotes incorporation and excretion of nitrogen in fecal bacteria, whereas the effect of dairy products is likely due to the influence of lactose on intestinal transit and pH (Center, 1998). The benefit of soy and dairy proteins cannot be attributed to their amino acid composition, since this is similar to that of meat and fish proteins. Exclusive use of soybean or lactose-containing dairy protein diets is generally not advocated in dogs, since they have low palatability and can cause diarrhea, although this is less significant when purified proteins are used.

Figure 6. Comparable quantities of indigestible protein in different sources of protein used in dog food (Source: Royal Canin).

The Role of Branched Chain Amino Acids

BCAA supplementation has been used to improve protein and energy utilization and HE in people with advanced liver disease, since a decreased plasma ratio of BCAA to AAA has been considered an important pathogenetic factor in HE. Results however have been mixed (Als-Nielsen et al., 2003; Marchesini et al., 2003), and it is now thought that any beneficial effect of BCAA supplementation is mostly related to improvement of the nutritional status, likely due to a stimulating effect on hepatocyte growth factor, favoring liver regeneration (Bianchi et al., 2005). A study in dogs showed no efficacy on HE from a diet high in BCAA and low in AAA, and it was concluded that the total protein intake was more important than dietary amino acid profile (Meyer et al., 1999). At present, BCAA supplements are unlikely to be of benefit in the management of canine liver disease, in view of their expense and questionable efficacy.

Fiber

Moderate quantities of dietary fiber can have several beneficial effects in liver disease. Soluble fiber is of particular benefit in managing HE. Colonic fermentation of soluble fibers such as fructo-oligosaccharides, beet pulp and gums lowers the intraluminal pH and thus reduces the production and absorption of ammonia, the effect of which is similar to that of lactulose. Colonic fermentation also favors the growth of acidophilic bacteria that produce less ammonia and promote incorporation and excretion of ammonia in fecal bacteria (e.g., Lactobacillus spp). Fiber (both soluble and insoluble) binds bile acids in the intestinal lumen and promotes their excretion. Insoluble fibers (lignin, cellulose, hemicellulose) act by normalizing transit time, whereas they can also prevent constipation and bind toxins. Diets containing soluble fiber and some insoluble fiber should therefore be useful in the long-term dietary management of dogs with HE (Marks et al., 1994; Center, 1998).

Minerals

Potassium

Hypokalemia is a common precipitating cause of HE in dogs with liver disease (Center, 1998). It occurs due to a combination of anorexia, vomiting or diarrhea, or excessive use of diuretics in the management of ascites. Diets for dogs with liver disease should therefore be potassium replete. Anorectic dogs may need supplementation by either intravenous administration of potassium chloride (10 - 40 mEq/500 ml fluids, depending on serum potassium) or oral potassium gluconate (0.5 mEq/kg once or twice daily). Potassium citrateshould be avoided because of its alkanizing properties, since alkalosis can aggravate HE.

Sodium

Abnormalities in sodium balance are less frequent, but moderate restriction of dietary sodium (less than 0.5 g/1000 kcal) is recommended in dogs with ascites and/or portal hypertension.

Trace Elements

Zinc

Zinc is an essential trace metal involved in many metabolic and enzymatic functions of the body. Zinc benefits the urea cycle and central nervous system neurotransmission, has clear hepatoprotective effects against a variety of hepatotoxic agents, and has antioxidant functions (Marchesini et al., 1996). Diets high in zinc (>43 mg/1000 kcal) are therefore useful for all patients with liver disease. Additional zinc supplementation may furthermore be useful to prevent hepatic copper accumulation in copper hepatotoxicosis, since dietary zinc induces an increase in the intestinal metal-binding protein metallothionein. Dietary copper then binds to the metallothionein with a high affinity that prevents its transfer from the intestine into the blood. When the intestinal cells die and are sloughed, the metallothionein bound copper passes out through the stool, thus blocking copper absorption (Sokol, 1996).

Dietary supplementation with zinc in patients with severe liver disease is done empirically with doses similar to those used in dogs with copper hepatopathies. Zinc is available as zinc acetate (2 - 4 mg/kg per day), sulfate, gluconate (3 mg/kg per day) and methionine. It is administered divided into two or three daily doses, and can be used as a dietary supplement (Brewer et al., 1992). Zinc should be given on an empty stomach and should not be given in combination with copper chelators. Toxicity other than occasional vomiting is minimal and the acetate salt may cause fewer GI signs.

Many liver diseases result in increased generation of free radicals and oxidant stress. Supplementation with antioxidants will therefore help to reduce oxidative liver injury.

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

Copper

Diets low in copper are recommended for dog breeds known to be prone to hepatic copper accumulation, especially Bedlington Terriers, and for dogs with documented increased hepatic copper (Table 8). Restriction of dietary copper in itself does little to lower increased hepatic copper levels, but it is an additional adjunct to decoppering therapy such as d-penicillamine and zinc.

Vitamins

B Vitamins

B Vitamins are often empirically supplemented at double maintenance dose, based upon recommendations for people with liver disease.

Vitamin C

The diet should contain adequate levels of vitamin C in order to compensate for failing hepatic synthesis and to take advantage of the antioxidant properties of vitamin C. Most commercial pet foods contain adequate amounts, and additional supplementation should only be necessary in case of severe fat malabsorption (Laflamme, 1999). Mega doses of vitamin C should be avoided in dogs with copper storage hepatotoxicity, since it can function as a pro-oxidant in the presence of high concentrations of heavy metals (Sokol, 1996).

Vitamin E

Vitamin E is an important endogenous free radical scavenger that protects against oxidative injury. There is evidence that oxidative damage from free radical formation plays an important role in the pathogenesis of liver disease. In particular, abnormal concentrations of bile acids, accumulation of heavy metals such as copper and iron, and inflammation can cause free radical generation and oxidant stress in the liver. Supplementation with vitamin E (400 - 600 IU/day) is especially indicated in cholestatic and copper-associated 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 is preferred, since a certain level of enteric bile acids are required for its absorption.

Vitamin E supplementation can reduce free radical or oxidant injury in many types of liver disease and may prevent progression of disease.

Vitamin K

Vitamin K deficiency is mostly relevant in cholestatic disorders, although it may also become depleted in severe chronic liver disease. Vitamin 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 - 1.0 mg/kg subcutaneously every 12 hours) (Laflamme, 1999). The same dose can be given biweekly or monthly in chronic disorders in which continued repletion of vitamin K is required.

Antioxidants

Chronic hepatitis and fibrosis, cholestatic liver disease and heavy metal hepatotoxicity are all known to be associated with increased generation of free radicals, and this is likely also the case in other types of liver disease (Britton & Bacon, 1994; Feher et al., 1998). Adequate dietary levels of antioxidants such as vitamins E and C, as well as taurine, are essential to minimize oxidative injury. A combination of dietary antioxidants is better than a single one, since they appear to act synergistically (Figure 7). A good balanced diet should also contain nutrients such as zinc, manganese and selenium, which are normally incorporated in enzymatic antioxidant systems (Sokol, 1996).

Figure 7. Cellular free radical scavengers. The intake of highly diverse antioxidants acting in synergy helps improve the protection of the cell’s various sensitive points and optimize protection against oxidation.  

S-Adenosylmethionine (SAMe) may also be helpful in reducing oxidative injury (Davidson, 2002). It is a precursor of glutathione, an important hepatic antioxidant enzyme that is often reduced in dogs with liver disease. Oral administration helps to replenish hepatic glutathione stores and may thus improve antioxidant function. In addition, SAMe has anti-inflammatory properties (Center et al., 2002).

Phosphatidylcholine (PC) is a phospholipid that is one of the components of bile required for normal bile acid transport and a building block for cell membranes. Its hepatoprotective actions are thought to be by improvement of membrane integrity and function (Twedt, 2004). Based on its multiple mechanisms of action, this nutrient may be beneficial for chronic liver disease associated with oxidative stress, but it has not yet been validated for use in dogs.

Silymarin is the active component of milk thistle, and is thought to have antioxidant and free radical scavenging properties for various types of liver disease, as well as a protective agent against various hepatotoxicities (Saller et al., 2001). There are currently limited clinical studies evaluating its efficacy in dogs with liver disease. Suggested doses range from 50 to 250 mg/day (Twedt, 2004).