Nutritional Modulation of Cardiac Disease

[malernee]

Nutritional Modulation of Cardiac Disease
ACVIM 2003
Lisa M. Freeman, DVM, PhD, DACVN
North Grafton, MA

INTRODUCTION

Nutrition can be an important adjunct to medical therapy in dogs and cats with cardiac disease. However, the role of nutrition has changed dramatically in recent years. In the past, when few cardiac medications were available, dietary sodium restriction was one of the major therapies for animals with congestive heart failure (CHF) and little consideration was given to other dietary factors. Now, the role of other nutrients in modulating cardiac disease is becoming more apparent and optimal feeding of the cardiac patient is more complicated than simply preventing nutrient deficiencies and excesses. Therefore, the purpose of this lecture is to review current information on the role of various nutrients in cardiac disease.

CARDIAC CACHEXIA

Cardiac cachexia is a common problem in dogs with CHF. Cachexia involves a loss of lean body mass which has direct and deleterious effects on strength, immune function, and survival. Cachexia sometimes is thought of as the classic end-stage picture of an emaciated dog or cat. In fact, cachexia is the process of lean body mass loss that can be very subtle initially and can even occur in an obese animal. Early recognition of cachexia may provide better opportunities to manage it effectively.

Anorexia, increased energy requirements, and metabolic alterations all contribute to the syndrome of cardiac cachexia. The anorexia may be secondary to fatigue, dyspnea, medication toxicity, or unpalatable diets. Anorexia, for example, is present in up to 75% of dogs with heart disease. However, it is the inflammatory cytokines, particularly tumor necrosis factor alpha (TNF), interleukin-1 beta (IL-1), and interleukin-6 (IL-6), that appear to be the primary mediators of cachexia. These inflammatory cytokines directly cause anorexia, increase energy requirements, and increase the lean body mass loss. Tumor necrosis factor, IL-1, and IL-6 also cause cardiac myocyte hypertrophy and fibrosis and have negative inotropic effects so may directly contribute to progression of disease.

Since inflammatory cytokines are elevated in CHF, a logical approach to treating patients would be to block these cytokines. One nutritional approach to reducing inflammatory cytokines is n-3 polyunsaturated fatty acid supplementation. Fish oil, which is high in n-3 fatty acids, can decrease cytokine production in dogs with CHF and improve cachexia. In some, but not all dogs with CHF-induced anorexia, fish oil supplementation improves food intake.In addition, reduction of cytokines has been correlated with survival in dogs with CHF. More specific anti-cytokine agents currently are being studied in people with CHF but, to this point, the results have been disappointing.

NUTRITIONAL EXCESSES

Sodium

Sodium excretion is reduced even in early cardiac disease so sodium restriction is typically recommended for dogs and cats with heart disease. However, dietary sodium restriction can further activate the renin-angiotensin-aldosterone system so it is not clear whether sodium restriction in early heart disease is beneficial or harmful. Although one study in dogs with CHF showed that measures of cardiac size decreased significantly on a low-sodium diet, the effect of low sodium diets on survival or progression of disease has not been studied.

Potassium

Angiotensin converting enzyme (ACE) inhibitor therapy has gained widespread use in the management of dogs with CHF. These drugs cause increased serum potassium and some animals develop hyperkalemia. Spironolactone, now used in some dogs and cats with heart disease, is an aldosterone antagonist and a potassium-sparing diuretic. Animals receiving ACE inhibitors or spironolactone can develop hyperkalemia. As some commercial cardiac diets contain increased potassium concentrations to counteract the theoretical potassium loss due to diuretics, these diets can contribute to hyperkalemia.

NUTRITIONAL DEFICIENCIES/NUTRITIONAL PHARMACOLOGY

At one time, deficiencies of nutrients such as thiamine and selenium were a common cause of cardiac disease in people. These deficiencies are now uncommon although there may be a number of examples in dogs and cats which still are important. There also are some nutritional deficiencies that can develop secondary to the cardiac disease and its treatment. Finally, supplementing certain nutrients may provide benefits above and beyond their nutritional effects (i.e., nutritional pharmacology). It is not always clear whether the benefits of a nutrient are the result of correcting a deficiency or pharmacologic effects.

Protein and Amino Acids

Protein

Recommendations for restricting the dietary protein intake of animals with CHF were once common. The rationale behind this recommendation was to reduce the "metabolic stress" on the kidneys and liver. There is no evidence that protein restriction is necessary for dogs and cats with CHF and, in fact, it probably is deleterious since these patients are predisposed to loss of lean body mass. Unfortunately, many people recommend a diet designed for renal disease for animals with heart disease because many renal diets are restricted in sodium. But protein is restricted even in some diets designed specifically for dogs with cardiac disease. Unless severe renal dysfunction is present, high-quality protein should be fed to meet canine maintenance requirements.

Taurine

There has been a dramatic reduction in cases of feline dilated cardiomyopathy (DCM) since the late 1980's when increased dietary supplementation of taurine was instituted after the landmark research of Pion, et al. Most of the current cases of feline DCM are not taurine deficient but taurine deficiency should be suspected in all cases of feline DCM. Cats that have been fed a poor quality, homemade, vegetarian, or otherwise unbalanced diets are at risk for taurine deficiency.

Taurine deficiency is now suspected in some cases of canine DCM. Unlike cats, dogs are able to synthesize adequate amounts of taurine and so are not thought to require dietary taurine. Most dogs with DCM do not have taurine deficiency, but low taurine concentrations have been found in some dogs with DCM, most commonly reported for the American Cocker Spaniel, Golden Retrievers, Labrador Retrievers, Newfoundlands, Dalmatians, Portuguese Water Dogs, and English Bulldogs. Taurine deficiency in dogs may be related to dietary factors as it is thought to be more common in dogs eating high fiber or certain lamb and rice based diets and has been induced by feeding a low protein, low taurine diet long-term to dogs. Taurine deficiency also may be the result of increased renal or fecal loss of taurine or other metabolic defects present in certain breeds. Taurine supplementation (with or without carnitine supplementation) may be beneficial in some dogs with taurine deficiency but, even in dogs that respond, the response generally is not as dramatic as in taurine deficient cats with DCM. The exact role of taurine in canine DCM still is unclear and some of the potential benefits may be due to its positive inotropic effects or role in calcium regulation in the myocardium.

Arginine

Nitric oxide is an endogenous vascular smooth muscle relaxant. It is synthesized from L-arginine and molecular oxygen and is catalyzed by the enzyme, nitric oxide synthase (NOS). There are three forms of NOS, inducible NOS (iNOS), endothelial NOS (eNOS), and neuronal NOS (nNOS). eNOS and nNOS are constitutive forms and are always produced in low levels. eNOS is required for maintenance of normal vascular tone and as a physiologic messenger. iNOS, on the other hand, is inducible by a variety of inflammatory mediators including the cytokines, TNF and IL-1, and free radicals. High levels of iNOS are induced as a mediator of the inflammatory response and in the host defense mechanism. Circulating nitric oxide is elevated in people, dogs, and cats with CHF.But, while iNOS is up-regulated in patients with CHF producing high circulating levels of nitric oxide, eNOS is actually down-regulated, thus reducing endothelium-dependent vasodilation. Arginine supplementation has been shown to improve endothelial dysfunction in people with CHF, with no negative effects on cardiac contractility or other echocardiographic variables.

Fat

n-3 polyunsaturated fatty acids

Fat provides calories and increases the palatability of pet foods but it also can significantly affect immunological, inflammatory, and hemodynamic parameters. The n-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are normally in low concentrations in the plasma membrane but levels can be increased by a food or supplement enriched in n-3 fatty acids. Dogs with CHF have been shown to have plasma fatty acid abnormalities, including decreased concentrations of EPA and DHA compared to normal dogs and fish oil supplementation can normalize these plasma fatty acid abnormalities. There are a number of potential benefits of n-3 fatty acids supplementation. The eicosanoids derived from n-3 fatty acids are less potent inflammatory mediators than those from n-6 fatty acids and n-3 fatty acids decrease production of TNF and IL-1. Additionally, n-3 fatty acids have been shown to have anti-arrhythmic properties.

Vitamins

B vitamins

Thiamine deficiency is known to be a cause of cardiomyopathy in people but there has been little investigation into the role of B vitamins as a cause of heart disease in dogs and cats. Anorexia and urinary loss of water soluble vitamins can contribute to low B vitamin concentrations in patients with heart failure. In people, over 90% of patients with CHF in one study had low thiamine concentrations. In one study of cats with cardiomyopathy vitamin B12, but not vitamins B6 or folate, was significantly lower compared to healthy controls, an effect that was unrelated to diet or furosemide use.However, in another study of cats with HCM folate, but not vitamin B12, was significantly lower compared to controls.

Minerals

Magnesium

Magnesium plays an important role in normal cardiac function. Hypomagnesemia can play an important role in a variety of cardiovascular conditions including hypertension, coronary artery disease, congestive heart failure, and cardiac arrhythmias.Some cardiac drugs are associated with magnesium depletion so animals with CHF can be at increased risk for hypomagnesemia. Hypomagnesemia can increase the risk of arrhythmias, decrease cardiac contractility, cause muscle weakness, contribute to renal potassium loss, and can potentiate the adverse effects of certain cardiac medications. Hypomagnesemia has not been a consistent finding in studies of animals with heart disease but this may be because serum magnesium concentrations are a poor indicator of total body stores.

Other Nutrients

L-Carnitine

L-Carnitine is critical for fatty acid metabolism and energy production and is concentrated in skeletal and cardiac muscle. Carnitine deficiency is associated with primary myocardial disease in a number of species, including a family of boxer dogs. Anecdotal reports exist regarding the efficacy of carnitine in canine DCM, but no blinded prospective studies have been done so a causative role has not been established. Even if carnitine deficiency is not the inciting cause of DCM, L-carnitine supplementation could be beneficial by improving myocardial energy production. In human DCM patients, most studies of L-carnitine have not been well-controlled. However, one randomized, double-blind, placebo-controlled study showed improved three-year survival in human DCM patients receiving 2 gm/day L-carnitine.

Coenzyme Q10

Coenzyme Q10, like carnitine, is a cofactor in a number of reactions required for energy production but is also an antioxidant. There are many anecdotal reports of benefits to coenzyme Q10 supplementation but controlled prospective studies are necessary to accurately judge the efficacy of this product. Most human studies of coenzyme Q10 supplementation have not been well-controlled and results are conflicting. Possible reasons for the reported benefits of supplementation include correction of a deficiency, improved myocardial metabolic efficiency, or increased antioxidant protection.

Antioxidants

Reactive oxygen species are a normal by-product of oxygen metabolism and are typically adequately compensated for through the production of endogenous antioxidants. However, some investigators have hypothesized that an imbalance between oxidant production and antioxidant protection could increase the risk for certain types of heart disease.Antioxidants are produced endogenously but also can be supplied exogenously with either enzymatic antioxidants (e.g., superoxide dismutase, catalase, glutathione peroxidase) or oxidant quenchers (e.g., vitamin C, vitamin E, glutathione, and β carotene). In one study of dogs with DCM, oxidative stress increased and vitamin E concentrations decreased with more severe disease. A recent study evaluated dogs with DCM or chronic valvular disease (CVD) for antioxidant status and oxidative stress. Parameters of oxidative stress included F2-isoprostanes, malondialdehyde, and protein carbonyls. Measures of antioxidant status included glutathione peroxidase, glutathione, vitamins C and E, and oxygen radical absorbance capacity (ORAC). The results of this study will be presented.

GENERAL DIET ISSUES

When selecting a diet for patient with cardiac disease, it is important to find one that has the desired nutritional properties for the individual animal. Nearly two-thirds of dogs with heart disease in one study had concurrent diseases that could affect dietary selection. The presence of partial or complete anorexia, which occurs in many animals with CHF, can dramatically alter diet choice. It also is important to devise an overall dietary plan that meets the owner's expectations. This includes finding a diet that the owner perceives the pet to enjoy, providing acceptable treats, and devising a satisfactory method for administering medications. In one study, over 90% of dogs with heart disease received treats and these treats were often high in sodium. In addition, the majority of people administering medications to their dogs use foods as a way to administer the medication. Therefore, including recommendations on appropriate treats and methods of administering medications is an important part of a successful nutritional program.

"CARDIAC" DIETS

There currently are a number of commercial veterinary diets available that are specifically designed for animals with cardiac disease. Specific characteristics of these foods vary, but they usually are mildly to severely restricted in sodium and generally contain increased levels of B vitamins. Some cardiac diets also may be enriched with other nutrients. The author and colleagues at Tufts University School of Veterinary Medicine currently are evaluating the effects of a mildly sodium restricted cardiac diet that is enriched with taurine, carnitine, arginine, n-3 fatty acids, and antioxidants.

REFERENCES

References are available upon request.

Speaker Information
(click the speaker's name to view other papers and abstracts submitted by this speaker)
Lisa M. Freeman, DVM, PhD, DACVN
SVM
Tufts University
200 Westboro Rd.
N. Grafton, MA 01536