View source for Omega-3 Fatty Acids - Nutrition

==What are Omega-3 Fatty Acids?==
[[File:Omega 3s labelled.jpg|right|400px]]
Omega-3 [[Fatty Acids Overview - Nutrition|fatty acids]] are a family of '''polyunsaturated straight-chain hydrocarbons''' that have a double bond in the third carbon-carbon bond (n-3) when counted from the methyl end of the molecule. Only plants have the ability to add double bonds in the n-3 position. There is speculation that fatty acids belonging to the n-3 family, specifically alpha-linolenic acid and docosahexaenoic acid, exhibit essential fatty acid activity in dogs and cats.

'''Alpha-linolenic acid (ALA)''' is an 18 carbon chain with double bonds at the n-3, n-6 and n-9 positions (written as 18:3n-3) that accumulated in skin phospholipids;<ref name ="Rees">Rees CA, ''et al.'' (2001) '''Effects of dietary flax seed and sunflower seed supplementation on normal canine serum polyunsaturated fatty acids and skin and hair coat condition scores. '''''Vet Dermatol'';12:111-117.</ref> '''docosahexaenoic acid (DHA)''' is a 22 carbon chain with doubles bonds at the n-3, n-6, n-9, n-12, n-15, and n-18 positions (written as 18:6n-3) that accumulates in the [[Eye - Anatomy & Physiology#The Wall (retina, uvea and sclera)|retina]] during growth and development.<ref name="Zicker">Zicker SC, ''et al.'' (2012)''' Evaluation of cognitive learning, memory, psychomotor, immunologic, and retinal functions in healthy puppies fed foods fortified with docosahexaenoic acid–rich fish oil from 8 to 52 weeks of age. '''''JAVMA'' 2012;241:583-594.</ref> Alpha-linolenic acid undergoes an initial desaturation by hepatic Δ-6 desaturase followed by elongation and another desaturation to form '''eicosapentaenoic acid (EPA; 20:5n-3)'''.<ref name="Dunbar">Dunbar BL and Bauer JE. (2000) '''Conversion of essential fatty acids by delta-6 desaturase enzyme in dog liver microsomes. '''''J Nutr ''2000;132:1701S-1703S.</ref> Dogs have the ability to convert modest amounts of ALA to EPA and supplementing with dietary ALA has been shown to increase plasma EPA levels in dogs;<ref name="Bauer">Bauer JE, ''et al.'' (1998)''' Dietary Flaxseed in Dogs Results in Differential Transport and Metabolism of (n-3) Polyunsaturated Fatty Acids.''''' J Nutr'' 1998;128:2641S-2644S.</ref> cats are unlikely to synthesise significant amounts of EPA from ALA given their limited hepatic Δ-6 desaturase enzyme activity.<ref name ="Sinclair">Sinclair AJ, ''et al.'' (1981)''' Essential fatty acid deficiency and evidence for arachidonate synthesis in the cat.''''' Br J Nutr'' 1981;46:93-93.</ref> Eicosapentaenoic acid is further elongated to form '''docosapentaenoic acid (DPA)''', which is released into circulation and taken up by the retina and brain where it is converted to '''docosahexaenoic acid (DHA)'''.<ref name="Alvarez">Alvarez RA, ''et al''. (1994) '''Docosapentaenoic acid is converted to docosahexaenoic acid in the retinas of normal and pred-affected miniature poodles. '''''Inv Ophthal Vis Sci ''1994;35:402-408.</ref>,<ref name="Pawlosky7">Pawlosky R, ''et al.'' (1994)''' Essential fatty acid metabolism in the feline: relationship between liver and brain production of long-chain polyunsaturated fatty acids.''''' J Lip Res'' 1994;35:2032-2040.</ref>

==Why are they Important?==
Alpha-linolenic acid works in conjunction with linoleic acid (LA) to help maintain [[Skin - Anatomy & Physiology|skin]] and [[Hair - Anatomy & Physiology|hair]] coat quality;<ref>Bauer JE. (2007) '''Responses of dogs to dietary omega-3 fatty acids. '''''JAVMA'' 2007;231:1657-1661.</ref> EPA is incorporated into the lipid bilayer of cell membranes along with [[Omega-6 Fatty Acids - Nutrition|arachidonic acid (AA)]] and may dampen inflammatory reactions;<ref>Raphael W and Sordillo LM. (2013) '''Dietary Polyunsaturated Fatty Acids and Inflammation: The Role of Phospholipid Biosynthesis.''''' Int J Mol Sci'' 2013;14:21167-21188.</ref> DHA is [[Nutrition Glossary#Conditionally Essential Nutrients|conditionally essential]] for normal brain and retinal development in puppies and kittens.<REF NAME="Zicker" /><ref name="Heinemann">Heinemann KM and Bauer JE. (2005) '''Docosahexaenoic acid and neurologic development in animals '''''JAVMA ''2005;228:700-705. </ref><ref name="Pawlosky11">Pawlosky R, ''et al.'' (1997) '''Retinal and brain accretion of long-chain polyunsaturated fatty acids in developing felines: the effect of corn-based maternal diets.''''' Am J Clin Nutr'' 1997;65:465-472.</ref>

'''Omega-6 and omega-3 fatty acids are in competition for the same metabolic enzymes''' and the ratio of omega-6 to omega-3 fatty acids as well as the total amount of each [[Nutrition Glossary#Polyunsaturated Fatty Acid|polyunsaturated fatty acid]] is an important consideration when evaluating dietary balance or when attempting to modify concentrations of these nutrients for health and disease management.

==Roles in the Body==
#'''Skin and Hair Coat:''' Epidermal keratinocytes secrete the LA-enriched phospholipid, ceramide, in both dogs and cats, which enhances cell cohesion and creates an effective water barrier.<ref>Elias PM, ''et al.'' (1980)''' The permeability barrier in essential fatty acid deficiency: Evidence for a direct role of linoleic acid in barrier function.''''' J Invest Dermatol ''1980;74:230-233. </ref> Increased intake of ALA may blunt the conversion of LA to AA,<ref name="Rees" /><ref name="Bauer" /> allowing for more LA to be incorporated into ceramide. Ratios of LA:ALA of 2.6:1 to 26:1 have been proposed for optimal skin and coat health.<ref name="NRC">National Research Council (NRC). (2006) '''Fat and Fatty Acids In Nutrient Requirements for Dogs and Cats. '''2006 ''Washington, DC: National Academies Press'' p.81-110.</ref>
#'''[[Inflammation]]:''' Eicosapentaenoic acid is incorporated into cellular membrane and competes with AA for cyclooxygenase (COX) and lipoxygenase (LOX) enzymes. Inflammatory [[Nutrition Glossary#Eicosanoids|eicosanoids]] produced from EPA (series-3 prostaglandins, prostacyclins and thromboxanes and series-5 leukotrienes) are less pro-inflammatory than those produced from AA metabolism.<ref name="NRC" /> Though not considered an essential fatty acid, increased intake of EPA in conjunction with a decrease in AA intake has been suggested as an aid in the management of inflammatory conditions such as [[Contact Dermatitis|allergic dermatitis]],<ref>Mueller RS, ''et al.'' (2005) '''Plasma and skin concentrations of polyunsaturated fatty acids before and after supplementation with n-3 fatty acids in dogs with atopic dermatitis.''''' Am J Vet Res'' 2005;66:868-73.</ref> nephritis,<ref>Brown SA, ''et al.'' (2000)''' Effects of dietary polyunsaturated fatty acid supplementation in early renal insufficiency in dogs. '''''J Lab Clin Med ''2000;135:275-286.</ref> and [[osteoarthritis]]<ref>Roush JK, ''et al. '' (2010)''' Multicenter veterinary practice assessment of the effects of omega-3 fatty acids on osteoarthritis in dogs. '''''JAVMA ''2010;236:59-66. </ref> in dogs. Supplementation of EPA has also been shown to be beneficial in older healthy dogs<ref>Hall JA, ''et al.'' (1999)''' Effect of dietary n-6 to n-3 ratio on complete blood and total white cell counts, and T cell populations in aged dogs. '''''AJVR ''1999;60:319-327.</ref><ref>Hall JA, ''et al.'' (1999)''' Influence of dietary long-chain n-3 fatty acids from menhaden fish oil on plasma concentrations of α-tocopherol in geriatric beagles.''''' AJVR ''1999;63:104-110.</ref> as well as those with heart disease.<ref>Freeman LM, ''et al. '' (1998) '''Nutritional alterations and the effect of fish oil supplementation in dogs with heart failure.''''' JVIM ''1998;12:440-448.</ref> Supplementation with higher levels of EPA in people undergoing cancer treatment may also result in a decrease in circulating [[Cytokines#Important cytokines|IL-6]] levels and improvement in lean body mass and appetite<ref>Barber MD, ''et al.'' (2001)''' Effect of a fish oil-enriched nutritional supplement on metabolic mediators in patients with pancreatic cancer cachexia.''''' Nutr Cancer'' 2001;40:118-24.</ref><ref>Fearon KC, ''et al.'' (2003)''' Effect of a protein and energy dense N-3 fatty acid enriched oral supplement on loss of weight and lean tissue in cancer cachexia: a randomised double blind trial.''''' Gut'' 2003;52:1479-86.</ref>. This specific effect of EPA on lean body mass and appetite has not been studied in dogs and cats, but EPA supplementation may be beneficial to help decrease inflammation secondary to radiation therapy in dogs with nasal tumours.<ref>Hansen RA, ''et al.'' (2011)''' Menhaden oil administration to dogs treated with radiation for nasal tumors demonstrates lower levels of tissue eicosanoids. '''''Nutr Res'' 2011;31:929-36.</ref> Additionally, dogs with [[lymphoma]] (stage 3a) had an improvement in short-term survival when fed a diet supplemented with EPA and DHA among other nutrient modifications<ref>Ogilvie GK, ''et al''. (2000)''' Effect of fish oil, arginine, and doxorubicin chemotherapy on remission and survival time for dogs with lymphoma: a double-blind, randomized placebo-controlled study. '''''Cancer ''2000;88:1916-28.</ref>. These effects have not been demonstrated in cats or in dogs with other types of cancers.
#'''Growth:''' Docosapentaenoic acid is taken up by brain and [[Eye - Anatomy & Physiology#The Wall (retina, uvea and sclera)|retinal tissues]] where it is converted to DHA. Docosahexaenoic acid is incorporated into retinal rods and brain tissue,<ref name="Zicker" /><ref name="Heinemann" /> and is conditionally essential for normal brain and retinal development.
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<center><gallery widths=450px heights=400px>
File:Omega 3.jpg|Role of omega-3 fatty acids in the body
File:Omega inflammation.jpg|EPA and AA compete for COX and LOX enzymes
</gallery></center>

==Consequences of Omega-3 Deficiency==
#'''Growth''': Puppies fed DHA deficient diets will grow normally, but show poor response to learned behaviour and visual acuity tests compared with puppies fed diets enriched with DHA.<ref name="Zicker" /><ref name="Heinemann" />  Kittens fed DHA deficient diets during gestation and lactation also have poor retinal and visual development.<ref name="Pawlosky11" />
#'''Adult Maintenance''': Clinical signs of ALA deficiency in adult dogs and cats are similar to LA deficiency (i.e. [[Seborrhea|seborrheic dermatitis]]), but are relatively mild and easy to miss.<ref name="NRC" />

==Toxicity==
Excess intake of ALA without a concurrent increase in LA resulting in a ratio below 2.6:1 (LA:ALA) may interfere with LA uptake into ceramide and the conversion of LA to AA,<ref name ="Zicker" /> but toxicity studies are lacking. 

Excess EPA intake can cause [[Platelet Abnormalities|platelet abnormalities]] and [[:Category:Haemostasis and Bleeding Disorders|bleeding disorders]] in cats,<ref>Saker KE, ''et al''. (1998) '''Manipulation of dietary (n-6) and (n-3) ratio fatty acids alters platelet function in cats. '''''J Nutr ''1998;128:2845S-2647S</ref> though this effect has not been demonstrated in dogs<ref>Boudreaux ML, ''et al.'' (1997)''' The effects of varying dietary n-6 to n-3 fatty acids ratios on platelet reactivity, coagulation screening assays, and antithrombin II activity in dogs.''''' JAAHA ''1997;33:235-243.</ref>. Dogs fed excessive amounts of the omega-3 long-chain polyunsaturated fatty acids, EPA and DHA, have shown impaired wound healing<ref>Mooney MA, ''et al.'' (1998)''' Evaluation of the effects of omega-3 fatty acid containing diets on the inflammatory stage of wound healing in dogs. '''''AJVR ''1998;59:859-863.</ref><ref>Scardino MS, ''et al.'' (1999)''' The effects of omega-3 fatty acid diet enrichment on wound healing. '''''Vet Derm ''1999;10:283-290. </ref> as well as impaired [[Innate Immunity Cellular Responses|cellular immunity]].<ref name="Wander">Wander RC, ''et al''. (1997)''' The ratio of dietary (n-6) to (n-3) fatty acids influences immune system function, eicosanoid metabolism, lipid peroxidation and vitamin E status in aged dogs.''''' J Nutr ''1997;127:1198-1205.</ref>

==Dietary Sources==
Specific seed and seed oils have varying concentrations of ALA; for example flaxseed oil provides 50% of the total fat as ALA while rapeseed (i.e. canola oil) provides 20% ALA<ref>USDA Nutrient Database. http://ndb.nal.usda.gov/ndb/ (accessed April 2015)</ref>. Terrestrial animal fats (associated with muscle, organ meat, eggs) are poor sources of ALA. Cold-water algae produce high concentrations of DHA, which is converted to EPA by marine fish after consumption; there is variation in EPA concentration between wild and farmed fish species. 
Recommendations for optimal ratios of omega-6 to omega-3 fatty acids are provided to pet food manufacturers, but an optimal amount of ALA has not been determined. Diets with higher levels of polyunsaturated fat (ALA, EPA and DHA) are prone to oxidative damage and require larger concentrations of dietary antioxidants to prevent rancidity (fat oxidation) during processing and storage.

==Diagnosing Omega-3 Fatty Acid Deficiency==
Diagnosis of ALA and DHA deficiency is difficult to make clinically and evaluation of diet is often used to demonstrate inadequate intake. Plasma lipid profiles may show low circulating concentrations of ALA and DPA though normal reference intervals have not been established.

==References==

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[[Category:Fatty Acids]]