Nutritional Management of Hyperlipidemia

Marked hyperlipidemia can be life-threatening and has been associated with development of pancreatitis, seizures, cholelithiasis, and peripheral neuropathies.^1-4 Prevalence of hyperlipidemia increases with age in predisposed breeds (e.g., miniature schnauzers and Yorkshire terriers) and can be detected during routine health screening of at-risk patients.^5,6

An association between hyperlipidemia and pancreatitis has been demonstrated in humans,^7,8 and although this association has long been theorized to occur in dogs,^9,10 only recently was an association demonstrated between marked hypertriglyceridemia (serum triglycerides levels  greater than 800 mg/dL) and increased canine pancreatic lipase immunoreactivity in dogs.^1-3 In addition, inborn errors in lipid metabolism or an underlying endocrine abnormality (e.g., diabetes mellitus, hypothyroidism, hyperadrenocorticism) can cause persistent, marked hyperlipidemia in dogs and cats in the fed or fasted state. Risk for development of pathologic hypertriglyceridemia may also be higher for at-risk individuals or breeds fed high-fat diets. Note, however, that increased postprandial serum cholesterol and triglyceride levels may be a benign incidental finding in dogs and cats.

Overview of Lipid Metabolism

Knowledge of fat metabolism is helpful for understanding the causes and treatments of hyperlipidemias. Pancreatic lipase is normally released into the duodenal lumen to degrade dietary triglycerides into free fatty acids and glycerol. These fatty acid products are further emulsified with bile salts to form a mixed micelle, which is then taken up by enterocytes. Within enterocytes, these mixed micelles are repackaged into chylomicrons, which are ultimately transported to the liver for further metabolism and assembly into protein and the fat-laden compounds called very low–density lipoproteins (VLDL). Chylomicrons originate exclusively from dietary fat and can remain increased in the blood for 2 to 12 hours after ingestion of a meal. After conversion to VLDL, these newly formed lipoproteins are then released into the circulation to deliver cholesterol, fatty acids, and other compounds (e.g., fat soluble vitamins) throughout the body. Fatty acids are removed from VLDL by lipoprotein lipase (LPL) on the surface of endothelial cells, thereby converting VLDL into low-density lipoproteins (LDL), which continue through the peripheral circulation. Cholesterol bound within circulating LDL is then transferred to high-density lipoproteins (HDL) for transport back to the liver. Unlike humans, dogs and cats lack the enzyme necessary to transfer cholesterol back to LDL; as such, most serum cholesterol in healthy dogs and cats is in HDL form. LPL production is increased by insulin, and LPL activity is stimulated by thyroid hormone and inhibited by glucocorticoids. 

Primary Disorders of Lipid Metabolism

Lack of LPL activity has been noted in cats with primary hyperchylomicronemia,¹¹ and decreased LPL activity in miniature schnauzers is believed to be associated with idiopathic hypertriglyceridemia.^3,5,6 One study found that approximately 32% of adult miniature schnauzers with no signs of pancreatitis had increased serum triglyceride levels greater than 800 mg/dL.⁶ The severity of hypertriglyceridemia increased with age, and approximately 75% of the miniature schnauzers older than 9 years were hyperlipidemic. In another study, miniature schnauzers with severe hypertriglyceridemia were 4.5 times more likely than those with normal serum triglyceride values to have markedly increased serum canine pancreatic lipase immunoreactivity levels (greater than 200 mg/dL).³ Hypercholesterolemia without hypertriglyceridemia has been reported in Shetland sheepdogs, rough-coated collies, Briards, and West Highland white terriers and is believed to be associated with decreased clearance of HDL particles by the liver.¹¹ LPL deficiencies have been documented in cats in New Zealand¹² and anecdotally in cats in the United States. Affected animals have increased levels of circulating triglycerides and cholesterol, and physical examination may detect decreased body fat stores, cutaneous xanthomas, or lipemia retinalis. 

Secondary Disorders of Lipid Metabolism

Hyperthyroidism is associated with decreased clearance of VLDL by the peripheral tissues and decreased clearance of LDL by the liver. Insulin deficiency with diabetes mellitus results in decreased production of LPL, activation of hormone-sensitive lipase (HSL), and a subsequent increase in circulating free fatty acids. Increased circulating cortisol, as seen with hyperadrenocorticism, has a similar net effect of increasing HSL activity and decreasing LPL activity. 

Diagnostic Approach to Hyperlipidemia

Diagnosis of hyperlipidemia is based on clinical and biochemical evidence of dyslipidemia. Clinical signs will vary with the individual patient. Miniature schnauzers with idiopathic hyperlipidemia can have markedly increased fasting serum triglyceride concentrations (greater than 1000 mg/dL) with or without hypercholesterolemia and increased liver enzyme values. Affected patients may exhibit clinical signs such as vomiting and abdominal discomfort, although a substantial subset of the population may have increased serum lipid concentrations without overt clinical signs of disease. Cats with hyperchylomicronemia may have cutaneous xanthomas, and dogs with hypertriglyceridemia may exhibit vomiting, abdominal pain, or seizures. Animals with secondary disorders of fat metabolism will have biochemical or clinical evidence of concurrent endocrinopathy. 

Care must be taken to look for any concurrent endocrinopathies that may predispose a patient to hyperlipidemia or that may affect results of dietary or medical intervention. Dietary fat intake can affect serum cholesterol and triglyceride levels for up to 12 hours, although it is uncommon for postprandial concentrations of either serum lipid to exceed 500 mg/dL. If increased serum cholesterol and/or triglyceride levels are seen on a nonfasted sample, testing should be repeated to confirm and quantify concentrations.¹³ 

Serum should be visually evaluated for gross lipemia because alteration in serum lactescence (milkiness) can be seen in samples with triglyceride concentration greater than 300 mg/dL. Hypercholesterolemia, however, will not change serum appearance because cholesterol carried as HDL is nonrefractile. A refrigeration test (chylomicron assay) can easily be performed on any serum sample to evaluate for dietary influence on hyperlipidemia. 

Increasing concentrations of serum cholesterol and/or triglycerides may also be picked up serendipitously on screening blood work for other conditions. Serum triglyceride concentrations are not reported on routine biochemistry profiles from all reference laboratories but should be requested for any patient with a history of persistent lipemia. 

Therapeutic Approaches

Hyperlipidemia may be resolved by treatment of any causative or contributing underlying disease(s) without the need for diet changes.¹⁴ However, diet histories should be collected for all patients with hyperlipidemia, as even animals with secondary hyperlipidemia may benefit from modest reductions in dietary fat intake. Chylomicrons result exclusively from dietary fat absorption, and if hyperchylomicronemia is present, dietary fat should be restricted below that being fed. Most nutrition resources recommend feeding a diet that provides no more than 24 grams of fat per 1000 kcal of diet (or 20% fat on a metabolizable energy basis), but decisions about the level of fat restriction should be made relative to the current diet. Crude fat percentages, which are reported as part of the guaranteed analysis on pet food labels, indicate the minimum grams of fat in every 100 grams of food but are not a reliable indicator of overall fat intake for 2 reasons: 1) these are minimum values that can be and are frequently exceeded; and 2) animals will eat to meet their daily energy need, and the total grams of food (and as such total grams of fat each day) will vary with the amount of food consumed. Commercial diets labeled as “lean” or “low fat” have legal maximum fat levels (e.g., 9% crude fiber as fed for products with a moisture content less than 20%), but diets that are labeled as “light,” “lite,” or “low calorie” are required only to provide fewer than 3100 kcal/kg as fed, with no qualifications on maximum fat contents.¹⁵ In the authors’ experience, knowledge of the patient’s current dietary fat intake is essential for therapeutic success, and to substantially affect serum lipid concentration, dietary fat intake must be decreased by at least 50% of the current intake. A limited number of commercial “low fat” therapeutic diets are sufficiently restricted for this condition, and an ultra–low-fat home-prepared recipe may be needed to fully control biochemical and clinical signs of disease. Home-prepared recipes should be formulated by a board-certified veterinary nutritionist to ensure that all other essential nutrient needs are met. Treats do not need to be eliminated from the diet but, if fed, should be limited to no more than 10% of the daily intake and have a fat content comparable to or below that of the primary diet. 

Dietary Supplements

Diet supplementation with fiber, fish oils, or niacin can also be considered for hyperlipidemia that is refractory to dietary fat restriction alone.

Fiber

Insoluble fibers add bulk to ingesta, resulting in decreased fat absorption, enhanced bile acid loss, and potentially reduced serum lipid concentrations. Increased guar gum (a soluble dietary fiber) has been shown to decrease serum cholesterol concentrations in healthy dogs.¹⁶

Fish Oils 

Fish oils are composed primarily of long-chain omega-3 polyunsaturated fatty acids, which are not efficiently incorporated into VLDL in the liver. Fish oil supplementation has been shown to decrease circulating VLDL in humans and dogs with increased endogenous production of this type of lipoprotein.¹⁷ The exact mechanism for the lipid-lowering effect of long-chain omega-3 fatty acids is not known but seems to be a combination of decreased hepatic triglyceride production, increased expression and activity of LPL, and increased overall β-oxidation of fatty acids.^18,19

Niacin 

At high doses, niacin has been shown to decrease liver synthesis of VLDL and decrease HSL activity.²⁰ It has been documented to aid in management of hyperlipidemias in humans, but evidence of its role in dogs and cats is lacking. Adverse effects of niacin administration in humans include “flushing” (characterized by erythema and pruritus), vomiting, diarrhea, and elevated liver enzyme levels.

Summary 

Clinical signs of markedly increased serum lipid concentrations may be overt (e.g., recurrent gastrointestinal signs, formation of cutaneous xanthomas) and will typically prompt a veterinary visit. However, many dogs and cats with moderate hyperlipidemia (serum triglycerides 600 to 1000 mg/dL) can exhibit only vague or subtle clinical signs that still warrant veterinary attention. Management of hyperlipidemia is aimed at controlling any concurrent endocrinopathies; limiting dietary fat intake; and, if needed for persistent hyperlipidemia despite dietary changes, providing medications or supplements that may limit endogenous lipid production. Hyperlipidemia can be associated with a number of familial and endocrine abnormalities, and the causes of hyperlipidemia should be investigated. If hyperlipidemia is found secondary to an endocrinopathy, initial management should be aimed at addressing the underlying disease state. In patients with primary hyperlipidemia, or secondary hyperlipidemia that fails to resolve with correction of the underlying disease state, dietary fat intake should be reduced relative to the current fat intake, taking into account all food and treat items. Home-prepared diet formulations formulated by a board-certified veterinary nutritionist should be considered for patients with hyperlipidemia that persists despite their eating a low-fat therapeutic diet.