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Veterinary Medical Uses And Sources of Omega-3 Fatty Acids
by John E. DeGroot, DVM, Veterinary Forum, May 1998

The healthful benefits of increased consumption of omega-3 fatty acids in human diets are widely accepted. The Second International Conference on the Health Effects of Omega-3 Polyunsaturated Fatty Acids in Seafood in Washington, D.C. (March 1990), concluded that there is "clear evidence of the role of these fatty acids in human growth and development and in health and disease to warrant recommending that human diets should include the omega-3 fatty acids." 1
In veterinary medicine as well, there is avid interest in the benefits of these fatty acids in such areas as inflammatory response, cardiology, and neoplasia in dogs, cats, horses, and other species. Understanding how these fatty acids can aid in certain medical conditions will help direct the clinician in recommending specific diets.

Medical Benefits of Omega-3 Fatty Acids
In general, dietary fatty acids are used as an energy source or in the production of hormones or incorporated into cell membranes.  Omega-6 fatty acids are classified as "ssential" in the diet; some researchers have theorized that omega-3 fatty acids are essential nutrients as well, but this theory has not been proven conclusively. Both these types of fatty acids may be acted upon by delta-desaturase enzymes to produce arachidonic acid from omega-6 fatty acids and eicosapentaenoic acid from omega-3 fatty acids. This competitive reaction is limited by relative supplies of omega-6 and omega-3 fatty acids and various delta-desaturase enzymes. (Nutritionists recommend that the ratio of omega-5:omega-3 fatty acids be decreased from currently recommended levels.) For these 18-carbon dietary fatty acids to be incorporated into cell membranes, they are elongated to 20-carbon omega-6 and omega-3 fatty acids and combined with glycerol phosphate to become arachidonic and eicosapentaenoic acids, then transported to the cell to become membrane phospholipids. 2

Inflammatory and Immune Response
Cellular injury leads to release of these 20-carbon fatty acids from their membrane phospholipids. Enzymatic synthesis produces a group of active compounds known as "eicosanoids" - a group of rapidly metabolized, locally acting hormones or autocoids that exert local biologic effect. The polyunsaturated metabolites of fatty acids, eicosanoids include hydroxylated eicosatetraenoic acids, leukotrienes, prostaglandins, and thromboxanes, to name a few. Synthesis occurs at the cellular level as needed. Eicosanoids are not stored by the body.
Arachidonic acid metabolism produces prostaglandins, thromboxanes, and leukotrienes that are pro-inflammatory, immunosuppressive, and proaggregatory and act as potent mediators of inflammation in type 1 hypersensitivity reactions. Eicosapentaenoic acid metabolism produces many of the same eicosanoids - but of a different series - that are less inflammatory, vasodilatory, and antiaggregatory and are not immunosuppressive. Ultimately, the relative amounts and types of each of the eicosanoids produced are regulated by competition for the active enzymes and the relative amounts of omega-6 and omega-3 fatty acids present at the injury site. Dietary manipulation of the omega-6:omega-3 ratio alters the tissue concentrations of these fatty acids and ultimately alters the response to tissue injury.
Use of omega-3 fatty acid dietary supplements in dogs and humans is effective in reducing pruritis, erythema, and inflammation associated with atopic dermatitis. Additionally, supplements seem to reduce the inflammatory symptoms associated with rheumatoid arthritis, cystic fibrosis, ulcerative colitis, and inflammatory bowel disease. 3, 4
Still, questions remain as to whether supplements are as effective as altering the entire diet's omega-6:omega-3 fatty-acid ratio. Some researchers suggest that dietary manipulation to achieve proper omega-6:omega-3 fatty-acid ratios improves the response rate of atopic animals. 2, 5
According to a two-year study from the Mayo Clinic and Foundation, Rochester, Minnesota, fish-oil treatments in human patients with idiopathic IgA nephropathy led to diminished rates of renal function due to decreased immunologic renal injury. 2, 6
Several reports support findings that omega-3 fatty acids influence immune reactivity by modulating cell function.7
Decreased dietary omega-6:omega-3 fatty-acid ratios can reduce the pathology associated with Mycoplasma hyopneumoniae infections in pigs. Severity of lesions in the lungs was inversely related to the amount of total dietary omega-3 fatty acid. 8

Cardiac Arrhythmia
Strong evidence exists that long-chain omega-3 fatty acids can prevent ventricular arrhythmia in rats, monkeys, and dogs through effects on ion channels in excitable tissue, reduction in myocardial oxygen requirements, and increased engergy efficiency. 1, 3 A review of the mechanisms and arrhythmia studies is available in the literature. 9 Additionally, moderate intake of omega-3 fatty-acid supplements can lower blood pressure modestly in mildly hypertensive patients. 4

Vascular Effects and Protection
A large epidemiologic study involving 852 men and extending over 20 years indicated that adequate fish intake (two meals per week) resulted in >50 percent reduction in coronary heart disease mortality compared with those who did not eat fish. 3 A study at the University of  Washington, Seattle, found intake of fish meal was associated with a 70 percent reduction in risk of primary cardiac arrest, generally linked to blood vessel occlusion. This reduction was attributed to decreased platelet activity, fibrinogen concentrations, proinflammatory mediators, and cell growth factors responsible for arterial-wall cell proliferation that causes narrowing of arteries. The reduced thromboxane production and increased prostacyclin production associated with omega-3 fatty acids through the metabolism of eicosapentaenoic acid result in decreased platelet aggregation and increased vessel dilation. 3

Omega-3 fatty acids reduce levels of plasma triglyceride and very-low-density lipoproteins (VLDL), with variable effects on low-density (LDL) and high-density lipoproteins (HDL). 3 Omega-3 fatty-acid supplements are also associated with increased renal perfusion. 10

Neoplasia
In carcinogen-induced and transplanted tumor models, omega-3 fatty acids reduced tumor development and omega-6 fatty acids stimulated tumor development. Omega-3 fatty-acid supplements inhibited or suppressed mammary tumor growth in animal models. In the mouse, human breast-cancer cell growth and metastasis were enhanced by omega-6 and reduced by omega-3 fatty acids. In fact, omega-3 fatty-acid supplements have been shown to inhibit tumorigenesis and metastasis in animals. 3,9

Omega-3 fatty acid-enriched diets helped reduce the complications of surgical intervention in patients with upper gastrointestinal (GI) neoplasia. They have decreased times of wound healing, prevalence of wound complications, and hospital stays and improved function of the GI tract. Omega-3 fatty acids also reduced radiation damage in the pig integument, specific to the normal, not malignant, cells. Omega-3 fatty-acid supplements have been shown to inhibit tumorigenesis and metastasis in animals and to kill certain types of cancer cells in animal models. 3

Infant Development
In both humans and animals, omega-3 fatty acids are essential in the development of the retina and visual cortex. 1 Supplementing maternal diets and infant formulas remains equivocal. 3

Natural Sources of Omega-3 Fatty Acids
Natural Sources of these fatty acids include plants and fish. Polyunsaturated fatty acids oxidize rapidly, making them difficult to process and handle. Fish or fish oils are unpalatable to many patients; are recognized as a common antigen in allergic humans; and can contain contaminants, such as heavy metals and pesticides. In humangs, the effectiveness of a dietary supplement containing fish oils is a question still under study.

Flax Seed
Flax is an unpalatable source of omega-3 fatty acid. It contains antinutrients, such as the cyanogenic glycoside, linamarin, which releases cyanide in moist, acidic conditions in the presence of the enzyme linatine. When metabolized, linatine forms a pyridoxine antagonist. These problems require that flax be processed and additional pyridoxine added to the final feed or diet.
Another disadvantage of flax oil, at least when used in food-animal feeds, is that it imparts a "fishy" taste to animal products, such as eggs. In spite of these difficulties, research has consistently shown that the omega-3 fatty-acid levels of a variety of animal tissues, dairy products, and poultry eggs can be improved when processed flax is included in animals'
diets. 11-15

Salvia hispanica
The seed of the Salvia hispanica plant, a nutritious, palatable alternative to flax and fish oil, provides a rich source of omega-3 fatty acids for those with an aversion or allergy to fish. High in lysine, S. hispanica has its own potent antioxidants, a complete amino acid profile, and high levels of soluble and insoluble fibers. 16 The naturally encapsulated seed requires no special handling or processing, contains no antinutrients, and leaves no fishy aftertaste. Naturally insect-resistant, S. hispanica is usually grown without pesticides. The seeds can directly and indirectly provide an increase in omega-3 fatty-acid consumption in both human and animal diets: Eggs produced on diets enriched with this seed showed an increase in omega-3 content and a decrease in total saturated fatty acids not seen in flax-fed chickens. 15
In an equine product sold as Tri-Omega, S. hispanica has recently attained Food and Drug Administration (FDA) and American Association of Feed Control Officials' approval for distribution as a food ingredient and source of fat, fiber, and protein.

Dietary Considerations
An understanding of the benefits of omega-3 fatty acids has only recently begun gaining momentum. At the Second International Conference on the Health Effects of Omega-3 Polyunsaturated Fatty Acids in Seafood, an organizing committee was formed to create an international society for the study of fatty acids to stimulate research, education, and clinical applications regarding omega-3 fatty acids. 1 At the Waltham International Symposium in Orlando, Florida (May 1997), several presentations were made on the current work, questions, and concerns of omega-3 fatty-acid supplements in dogs, cats, and horses. Topics included desaturation and transport of fatty acids, effects on platelegt function in the cat, general health benefits in the horse, and inflammatory dermatitis in the dog and cat. Research on the beneficial and detrimental effects of dietary omega-3 fatty acids is under way around the world in numerous disciplines and in various species.

In light of difficulties in producing, processing, handling, and feeding these fragile oils, neither human nor animal diets have changed dramatically in the West, where fresh, cold-water fish is not consumed in adequate amounts. Livestock are fed feed grain without specific regard given to the resultant increase in omega-6 fatty acid and total saturated fats in the final product. There is no readily available, stable, and safe form of omega-3 fatty acid for use in livestock. Processed foods, grain-fattened livestock and poultry, and hydrogenated vegetable oil contribute to increased omega-6 and decreased omega-3 fatty acid consumption in humans. This oversupply of omega-6 fatty acid in diets competitively inhibits the production of the important omega-3 fatty-acid metabolites.
Based on this principle of inhibited competition, nutritionists recommend decreasing the dietary ratio of omega-6:omega-3 from the present 15:1 to 5:1. The lower ratio can be reached by increasing omega-3 fatty acid consumption relative to omega-6 fatty acid through direct supplements or by eating products with substantial omega-3 fatty acid levels and by improving the omega-3 fatty acid levels in other food products.
It should be noted that guidelines regarding dietary levels of omega-3 fatty acids and the relative levels of omega-6 to omega-3 fatty acids have not been determined, and in fact, the FDA has not yet recognized omega-3 fatty acids as essential in the diet. Some pet food manufacturers have made recommendations for the omega-6:omega-3 ratio and subsequently altered dog food formulations by increasing the level of omega-3 to achieve a specific ratio to omega-6. 2

Concerns have been raised regarding long-term or high-dose supplements in pets, including increased risk of bleeding, impairment of linoleic acid metabolism through enzymatic competition, tissue damage secondary to lipid peroxidation in the absence of adequate body antioxidant levels, and detrimental effects of decreased inflammatory or immune response. 17 Omega-6:omega-3 ratios used in many of these studies are difficult if not impossible to achieve outside of laboratory settings.
Increased intake of omega-3 fatty acids in a diet may prove to be important in promoting better health. Much of the research on these substances is ongoing; some of it is inconclusive, but few researchers dispute the fact that we need to increase intake of omega-3 fatty acid to attain a reasonable omega-5:omega-3 ratio or the fact that this area of nutritional and medical research may hold a key to improved health for both humans and animals. For example, in two separate studies using eggs and dairy products from animals with increased omega-3 fatty acid levels, human ingestion of the products resulted in significantly higher levels of omega-3 and decreased triglycerides and LDL cholesterol. 18, 19 The question for pets and humans is whether supplements are as safe and effective as is altering dietary ratio.
Pet owners and veterinarians may hesitate to accept dietary supplement information as reliable because of the information and misinformation propagated by unscrupulous "health-food" suppliers regarding products that may prove unsafe or ineffective. This reluctance is exacerbated by the lack of food-supplement regulations and the lack of general information flowing to the public from the medical community regarding dietary recommendations and use of supplements. Food producers can improve the nutritional value of their products by increasing omega-3 fatty acids through the use of S. hispanica, flax, or fish oil. Additional research is needed and is ongoing in this area of nutrition to provide specific recommendations regarding total-body requirements of the polyunsaturated fatty acids and dietary supplements in both humans and animals.

 

References

  1. Marwick C. International foncerence gives boost to including omega fatty acids in diet. JAMA, 1990; 263:2153-2154.
  2. Reinhart G. Review of omega-3 fatty acids and dietary influences on tissue concentrations. In: Carey DP, Norton SA, Bolser SM, eds. Recent Advances in Canine and Feline Nutritional Research: Proceedings of the 1996 Iams International Nutrition Symposium. Wilmington, OH: Orange Frazier; 1996: 253-242
  3. Haumann BF. Nutritional aspects of omega-3 fatty acids. Inform: International News on Fats, Oils and Related Materials. 1997;8(5):428-447.
  4. Muggli R. Nutritional aspects of omega-3 long-chain polyunsaturated fatty acids. Agro-Food Industry Hi-Tech. 1997; (January/February):35-36.
  5. Dimski DS. Therapy of inflammatory bowel disease. In: Kirk's Current Veterinary Therapy XII. Philadelphia, PA: WB Saunders; 1995:727
  6. Donadio JV, Bergstralh EJ, Offord KP, et al. A controlled trial on fish oil in IgA nephropathy. N Engl J Med. 1994;331:1194-1200.
  7. Hughes DA, Southon S, Pinder AC. (Omega-3) polyunsaturated fatty acids modulate the expression of functionally associated molecules on human monocytes in vitro. J Nutr. 1996; 126:603-610.
  8. Turck JJ, Schoenlein IA, Watkins BA, et al. Dietary polyunsaturated fatty acid modulated response of pigs to Mycoplasma hyopneumoniae infection. J Nutr. 1996; 126:1541-1548.
  9. Nair SS, Leitch JW, Falconer J, et al. Prevention of cardiac arrhythmia by dietary (omega-3) polyunsaturated fatty acids and their mechanism of action. J Nutr. 1997; 127:383-393.
  10. Ogilvie GK, Fish oils and cancer: hot new information and anticancer diet. Paper presented at the Wild West Veterinary Concerence; Reno, NV; October, 1996.
  11. Kratzer FH. The use of flaxseed as a poultry feedstuff. University of California, Davis, Dept. of Avian Science, March 1996. Poultry Fact Sheet 21. http://www.ainet.com/epif/fact21.htm.
  12. Cherin G. Dietary linolenic acid alters the fatty acid components of lipid classes in swine tissues. J Agri Food Chem. 1995;43:2911-2916.
  13. Klose AA, Mecchi EP, Behman GA, et al. Chemical characteristics of turkey carcass fat as a function of dietary fat (article available upon request). Bureau of Agricultural and Industrial Chemistry. Agricultural Research Administration, USDA. 1951;354-359.
  14. Cherin G. Dietary linolenic acid and laying hen strain: fatty acids of liver, adipose tissue, white meat, dark meat, and egg yolk. J Agri Food Chem 1995; 43:2553-2555.
  15. Ayerza R. Coates W. An omega-3 fatty acid-enriched diet: influence on fatty acid composition, cholesterol and oil content of eggs (unpublished; article available upon request).
  16. Brown JH. The Rediscovery of Chia, A Nutritious Grain of Mesoamerica. Gilbert, AZ: International Flora Technologies; April 22, 1997.
  17. Hall JA. Potential effects of long-term consumption of (omega-3) fatty acids. Compend Cont Ed Pract Vet. 1996; 18:879-892.
  18. Noakes M. Modifying the fatty acid profiles of dairy products through feedlot technology lowers plasma cholesterol of humans consuming the products. Am J Clin Nutr. 1996; 63:42-46.
  19. Ferrier LK, Caston L. Leeson S. et al. Changes in serum lipids and platelet fatty acid composition following consumption of eggs enriched in alpha-linolenic acid. Food Res Internat. 1995; 25:263-268.

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