Fatty acids have a number of important roles in the body. These include, among others, serving as a source of fuel, transporting fat-soluble vitamins, serving structural functions as part of cell membranes, and being involved in cell regulation and signaling. Fatty acids are also used for management of disease, giving them a unique role as a nutraceutical, which is a nutrient that has properties of a drug.1,2 The objective of the information reported here is to provide an overview of topics related to fatty acids and to improve general understanding of these topics.
Fatty Acid Nomenclature
Fatty acids are hydrocarbon chains that can be described in a number of ways on the basis of their characteristics. One descriptive method is chain length or the number of carbons contained in a fatty acid. Fatty acids can be classified into 3 categories: short-chain (containing < 6 carbons), medium-chain (containing 6 to 12 carbons), or long-chain (containing > 12 carbons). Chain length can confer special properties to a fatty acid, and differences in chain length can affect the method of absorption from the gastrointestinal tract. Medium-chain fatty acids are mainly absorbed into the portal bloodstream and go directly to the liver from the gastrointestinal tract, whereas long-chain fatty acids are absorbed through a process involving the lymphatic system and go to the liver only after passing through the heart.3 These biological differences can result in different methods for disease management with fatty acids. For example, medium-chain triglycerides can be beneficial in patients with disorders of lipid digestion or absorption because they are absorbed via a different method.4
Fatty acids can also be classified as saturated or unsaturated, which describes the number of double bonds in a hydrocarbon chain. Saturated fatty acids contain no double bonds. Unsaturated fatty acids can be further characterized as monounsaturated (1 double bond) or polyunsaturated (≥ 2 double bonds). The number of double bonds in a fatty acid influences biological function. The number of double bonds can affect the melting point of a fatty acid, with more double bonds lowering the melting point.5 The number of double bonds also affects the state of fats at room temperature. Saturated fatty acids are solid at room temperature, whereas PUFAs are liquid at room temperature. Double bonds can also make membranes more fluid, which can in turn affect membrane properties.6
Unsaturated fatty acids can be further classified on the basis of the location of the first double bond relative to the methyl (omega) end of the fatty acid. Fatty acids can be omega-3 (n-3; first double bond between carbons 3 and 4 from the omega end), omega-6 (n-6; first double bond between carbons 6 and 7 from the omega end), omega-7 (n-7; first double bond between carbons 7 and 8 from the omega end), or omega-9 (n-9; first double bond between carbons 9 and 10 from the omega end).7 Omega-6 and omega-3 fatty acids are essential for mammals: they must be consumed in the diet because animals lack Δ-12 desaturase and Δ-15 desaturase that insert double bonds in the omega-3 and omega-6 positions.3,7 In general, omega-7 and omega-9 fatty acids are endogenously synthesized by Δ-9 desaturase, which desaturates between carbons 9 and 10 from the carboxyl end.8 Because omega-7 and omega-9 fatty acids can be endogenously synthesized, they are not essential in the diet of mammals.
Omega-6 and omega-3 PUFAs can also be described as long-chain PUFAs when they contain > 18 carbons (Figure 1). In general, the term long-chain PUFA refers to AA (eicosatetraenoic acid; 20:4n-6), EPA (20:5n-3), and DHA (22:6n-3), although there are other long-chain PUFAs such as docosapentaenoic acid (22:5n-3). A fatty acid may be referred to by its common name (eg, AA), systematic name based on chain length and number of double bonds (eg, EPA), or numerical name (eg, 20:4n-6 or 20:5n-3).5 Thus, PUFAs may be described by several terms, such as LA (octadecadienoic acid; 18:2n-6) or ALA (octadecatrienoic acid; 18:3n-3).
Essentiality of Omega-6 and Omega-3 Fatty Acids
Omega-6 and omega-3 fatty acids are considered essential dietary fatty acids for mammals. Omega-6 and omega-3 fatty acids are necessary for physiologic growth and function, and mammals are unable to endogenously synthesize them in adequate quantities3,7; therefore, essential fatty acids must be consumed in the diet. Nonessential fatty acids can be synthesized from other dietary fatty acids, provided the precursor fatty acids are consumed in the diet. Thus, fatty acids that can be produced in the body are considered nonessential because they can be made endogenously.
Plants can synthesize omega-6 and omega-3 fatty acids, which make them good dietary sources of essential fatty acids.3 Common dietary omega-6 fatty acids include LA and AA, whereas common dietary omega-3 fatty acids include ALA, EPA, and DHA. Algae can synthesize large amounts of omega-3 fatty acids, which make marine animals that consume algae a good source of EPA and DHA.9
Both LA and ALA are considered essential fatty acids for both dogs and cats, although the degree of essentiality is dependent on the life stage.3 In dogs, AA is synthesized from LA by desaturase and elongase enzymes (Figure 2). The first step in the desaturation of essential fatty acids is regulated by Δ-6 desaturase, which inserts a double bond between carbons 6 and 7 from the carboxyl end of the fatty acid.10 Cats have a dietary requirement for AA because of limited Δ-6 desaturase activity.11 It appears that DHA is conditionally essential for puppies and possibly also kittens; DHA plays a role in development of the nervous system.3
The same desaturase and elongase enzymes that convert LA to AA also convert ALA to EPA and DHA (Figure 2). Both EPA and DHA are of interest because of their proposed anti-inflammatory effects. Although ALA can be converted to EPA and DHA, this process is inefficient in dogs12 and virtually nonexistent in cats.7 Therefore, it may be prudent to supplement diets with EPA and DHA to reach required or clinically desired amounts of these fatty acids.13 In humans, synthesis of EPA as a result of conversion from ALA is < 6% and synthesis of DHA as a result of conversion from ALA is < 0.1%.14 In dogs, the conversion rate also is < 10%.15,16 Adequate amounts of EPA and DHA may be provided directly through the diet or by supplementation of the diet with EPA and DHA.
Schematic depiction of the chemical structures of important omega-3 and omega-6 fatty acids.
Citation: Journal of the American Veterinary Medical Association 246, 11; 10.2460/javma.246.11.1198
Schematic depiction of the pathways for desaturation and elongation of omega-3 and omega-6 fatty acids.
Citation: Journal of the American Veterinary Medical Association 246, 11; 10.2460/javma.246.11.1198
Clinical Signs of Fatty Acid Deficiency
Fatty acid deficiency occurs as a result of consuming extremely low-fat diets as well as diets deficient in essential fatty acids. There is rarely a fatty acid deficiency in animals consuming commercial diets fed to meet daily energy requirements, but deficiency could be seen in animals consuming unbalanced diets, homemade diets deficient in essential fatty acids regardless of total fat content, or ultra–low-fat diets. There can also be deficiency of essential fatty acids with severe caloric restriction. One common scenario whereby an essential fatty acid deficiency could develop would be a dog consuming a homemade diet with fatty acids provided from sources such as beef tallow, coconut oil, or olive oil, which do not have sufficient quantities of LA or ALA to meet daily requirements for essential fatty acids. Clinical signs of deficiency of essential omega-6 fatty acids include dermatologic disorders (alopecia, scaly skin, and an increased tendency to bruise), reproductive abnormalities (tubular degeneration of the testes in males and failure of queens to give birth to viable neonates), and poor growth.3,7,11,17 Clinical manifestations of dietary deficiency of omega-3 fatty acids are not as pronounced as those for omega-6 fatty acid deficiency and generally include nervous system abnormalities.3,18 In 1 case report,19 ALA deficiency developed in a 6-year-old child receiving a parenteral nutrition admixture deficient in ALA, which resulted in numbness, paresthesia, weakness, leg pain, and blurred vision. The serum ALA concentration in that patient was significantly lower than the concentration in clinically normal children, but serum EPA and DHA concentrations were not significantly different from control values.19 Because of the differences in requirements among life stages, clinical signs of fatty acid deficiency may be more commonly observed during demanding life stages, such as growth and gestation-lactation.
Special Functions of Long-Chain PUFAs
Long-chain PUFAs downstream of LA and ALA influence membrane fluidity and stability; more double bonds in phospholipid fatty acids lead to more fluidity of membrane structures.3,6 Membrane fluidity can affect both membrane structure and function.3 Certain tissues, depending on function, may concentrate long-chain PUFAs of the omega-6 or omega-3 class. For example, neurologic tissue tends to concentrate long-chain omega-3 PUFAs in myelin.3
Long-chain PUFAs including AA and EPA are essential for eicosanoid production. Eicosanoids are fatty acyl–derived metabolites, including prostaglandins, prostacyclin, thromboxane, lipoxin, and leukotrienes.3 Long-chain omega-3 PUFAs, especially DHA, are also involved in retinal, neural, and auditory development.20 Because of the multiple functions of long-chain PUFAs, small amounts of these fatty acids are recommended in the diet for all life stages.3 In addition, EPA and DHA have been used in the management of inflammatory and chronic diseases.2
Sources of Omega-6 and Omega-3 Fatty Acids
Sources of dietary omega-6 and omega-3 fatty acids include plants and animals. Fats stored in tissues of animals (terrestrial or aquatic animals) reflect dietary intake of that animal.3 For example, salmon fed vegetable oil may have a tissue fatty acid composition that differs from that of wild-caught salmon.21 In addition, different types of fish have differences in compositions of fatty acids and tissue ratios of n-6 to n-3 fatty acids,3 which likely are attributable to differences in diets consumed by the various species of fish. As a result, not all fish oils are equivalent and not all fish oils provide the same proposed health benefits. Omega-6 and omega-3 fatty acids are also found in other types of animals as well, including terrestrial animals. Fatty acid composition of animal tissue also depends on dietary composition in mammals. For example, finishing steers allowed to graze on pasture tend to have higher tissue concentrations of omega-3 fatty acids and lower tissue concentrations of omega-6 fatty acids, compared with tissue concentrations for finishing steers fed a typical grain-based diet in a feedlot.22
Plants also contain omega-6 and omega-3 fatty acids. Various amounts of LA and ALA can be found in plant products, including oil and seeds. Good sources of LA include corn oil and canola oil, whereas the fatty acids in flaxseeds are predominantly ALA. Plants contain little or no AA.3 Concentrations of PUFAs differ among types of plants, and plants and plant products can also contain other types of fatty acids, such as medium-chain fatty acids (eg, coconut oil) and monounsaturated fatty acids (eg, olive oil). Some types of marine algae contain DHA. Pet foods can also be a source of omega-3 fatty acids.
Sources of omega-3 fatty acids in nutritional products (ie, supplemental-type products) can differ widely. Supplement-type products range from fish oil capsules for humans to pet-specific EPA- and DHA-concentrated oils in capsule or liquid forms. In addition, human and pet supplement-type products vary in omega-3 fatty acid content. Some products contain substantial quantities of omega-6 fatty acids in addition to omega-3 fatty acids. When the goal is to provide supplemental EPA and DHA, fatty acid products that contain both omega-6 and omega-3 fatty acids are less likely to be effective because of lower concentrations of EPA and DHA in these products.
As mentioned earlier, not all fish oil is equivalent and not all products are the same. Differences among products can cause confusion for veterinarians and pet owners alike. Products containing vitamin A and vitamin D should be avoided in general, although it is not always indicated on a label that a product contains excessive amounts of vitamin A or vitamin D.
Doses of Omega-3 Fatty Acids
The dose of omega-3 fatty acids can be expressed in numerous ways. It can be expressed as the number of milligrams of total omega-3 fatty acids per kilogram of body weight, the number of milligrams of EPA and DHA per kilogram of body weight, the number of milligrams of EPA and DHA per kilogram of metabolic body weight (ie, [body weight]0.75), the dietary amount on a per-energy basis (g [or mg]/100 [or 1,000] kcal), or the dietary amount on a per-weight basis (g [or mg]/100 g of diet [as-fed basis or dry-matter basis]).13
Linoleic acid and ALA are in direct competition for the desaturase and elongase enzymes that result in downstream fatty acids (AA or EPA and DHA).12 Therefore, dietary excess or deficiency of LA versus ALA may influence the rate of conversion to longer-chain fatty acids. Dietary amounts of omega-6 versus omega-3 fatty acids can be expressed as a dietary ratio of n-6 to n-3 fatty acids or as absolute amounts as mentioned previously. However, the n-6–to–n-3 ratio can be misleading. The ratio includes total omega-6 and omega-3 fatty acids, including ALA. Because ALA does not have the same metabolic effects or benefits as those of EPA and DHA, a ratio for which the total n-3 portion includes a substantial amount of ALA is not metabolically identical to one that includes primarily EPA and DHA.
To the author's knowledge, there is no consensus about the appropriate manner in which to express doses of supplemental omega-3 fatty acids; this makes it complicated to interpret information about dosage amounts of omega-3 fatty acids. For example, products (including both pet foods and supplement-type products) advertised as containing omega-3 fatty acids may contain ALA but no EPA or DHA. This can be especially misleading when the n-6–to–n-3 ratio is used to express amounts of omega-3 fatty acids. However, there is an ongoing debate regarding whether the absolute quantity of EPA and DHA provided is more relevant than is the n-6–to–n-3 ratio. Some researchers support the use of a high absolute dose of omega-3 fatty acids,23 whereas other scientists support the use of a low n-6–to–n-3 ratio to modulate inflammation and disease.24,25
Assessment of Fatty Acid Status
In addition to assessing patients for clinical signs of fatty acid deficiency, plasma phospholipid and blood cell membrane fatty acid concentrations can be measured as an additional assessment tool. Fatty acid status can be used to assess response to treatment (eg, dietary or supplemental omega-3 fatty acids for modulation of disease), but it has not been commonly used in a clinical setting because of the technical expertise required and expense of the procedure. Experimentally, fatty acid status is used commonly to assess response to dietary modification. Fatty acid analysis is commonly performed on plasma or on platelet and erythrocyte membranes, likely because of the ease of collection of these blood components. In dogs, a correlation between plasma fatty acid concentrations and concentrations of fatty acids in erythrocyte membranes has been detected for omega-3 but not omega-6 fatty acids.26 Membranes of other cell types could be analyzed, but tissue collection is more difficult and invasive than is venipuncture, which limits the practicality of this method in research and clinical practice settings. The method for fatty acid analysis is described elsewhere.27,28
Safety and Regulatory Issues for Fatty Acid Products
Although fatty acid products have been used in the management of conditions in humans, dogs, cats, and horses, supplement-type products are not subject to the same regulatory laws as those for drugs. Health claims for supplement-type products are voluntary and are not regulated as carefully as are drug claims.29 In general, manufacturers of dietary supplement-type products are responsible for ensuring the safety of their products, and the FDA does not require proof of safety or efficacy to enable these products to be marketed. The Dietary Supplement Health and Education Act of 1994 holds the FDA responsible for taking action against unsafe dietary supplements for humans after they reach the market, but the FDA does not ensure accuracy of label claims unless the product is reported to be detrimental to the health of subjects.a
Supplement-type products for fatty acids, including omega-6 and omega-3 fatty acids, have been used in the management of disease and can be beneficial in the management of a number of inflammatory and other conditions.2 However, fatty acid products can have adverse effects in companion animals, similar to the adverse effects of drugs, which means that provision of supplemental fatty acids is not without risk. Adverse effects of supplemental omega-3 fatty acids include potential effects on coagulation and potential effects as a result of rancidity. Potential adverse effects for omega-3 fatty acids are discussed in detail elsewhere,30 but it is important to remember that other fatty acid products also have the potential to cause adverse effects (such as effects attributable to rancidity).
Clinical Summary
Although lipid biochemical processes are a complicated topic, veterinarians should have a basic understanding of fatty acids and their impact on health and disease in companion animals. It is important for veterinarians to understand that different sources and types of omega-6 and omega-3 fatty acids do not have the same functions, and that animals of all life stages require both omega-6 and omega-3 fatty acids in their diet. In addition to the fact that they are essential for physiologic tissue function, fatty acids can modulate disease and influence growth and development. Provision of supplemental omega-6 and omega-3 fatty acids can result in adverse effects.
ABBREVIATIONS
| AA | Arachidonic acid |
| ALA | α-Linolenic acid |
| DHA | Docosahexaenoic acid |
| EPA | Eicosapentaenoic acid |
| LA | Linoleic acid |
| PUFA | Polyunsaturated fatty acid |
US FDA. Dietary supplements. Available at: www.fda.gov/food/dietarysupplements/default.htm. Accessed Nov 9, 2014.
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