Changes

==1. What are Omega-6 Fatty Acids?==

==What are Omega-6 Fatty Acids?==

<span style="color:red">Omega-6 fatty acids are a family of polyunsaturated straight-chain hydrocarbons that have a double bond in the sixth carbon-carbon bond (n-6) when counted from the methyl end of the molecule. FIGURE SHOWING METHYL END, OMEGA BOND</span> <span style="color:red">Linoleic acid contains 18 carbons with double bonds at both the n-6 and n-9 positions (written as 18:2n-6). It undergoes further desaturation by hepatic Δ-6 desaturase to form gamma-linolenic acid (GLA; 18:3n-6), which is elongated and desaturated once more to form arachidonic acid (AA; 20:4n-6). SCHEMATIC?</span>  Linoleic acid (LA) is considered an essential fatty acid in both dogs and cats. Dogs are able to convert adequate amounts of LA to AA to meet requirements at all life-stages<ref>Dunbar BL and Bauer JE. Conversion of essential fatty acids by delta-6 desaturase enzyme in dog liver microsomes. J Nutr 2000;132:1701S-1703S.</ref>, cats however have limited hepatic Δ-6 desaturase enzyme activity<ref name="Sinclair">Sinclair AJ, et al. Essential fatty acid deficiency and evidence for arachidonate synthesis in the cat. Br J Nutr 1981;46:93-93.</ref><ref name="Rivers">Rivers JPW. Essential fatty acids in cats. J Small Anim Prac 1982;23:563-576.</ref><ref>Bauer JE. Fatty acid metabolism in domestic cats (Felis catus) and cheetahs (Acononyx jubatus). Proc Nat Soc 1997;56:1013-1024.</ref> and require a dietary source of AA to meet their metabolic needs. The dietary requirement for LA in cats is lower than dogs because LA is not used as a precursor for synthesis of AA.

<span style="color:red">Omega-6 fatty acids are a family of polyunsaturated straight-chain hydrocarbons that have a double bond in the sixth carbon-carbon bond (n-6) when counted from the methyl end of the molecule. FIGURE SHOWING METHYL END, OMEGA BOND</span> <span style="color:red">Linoleic acid contains 18 carbons with double bonds at both the n-6 and n-9 positions (written as 18:2n-6). It undergoes further desaturation by hepatic Δ-6 desaturase to form gamma-linolenic acid (GLA; 18:3n-6), which is elongated and desaturated once more to form arachidonic acid (AA; 20:4n-6). SCHEMATIC?</span>  Linoleic acid (LA) is considered an essential fatty acid in both dogs and cats. Dogs are able to convert adequate amounts of LA to AA to meet requirements at all life-stages<ref>Dunbar BL and Bauer JE. Conversion of essential fatty acids by delta-6 desaturase enzyme in dog liver microsomes. J Nutr 2000;132:1701S-1703S.</ref>, cats however have limited hepatic Δ-6 desaturase enzyme activity<ref name="Sinclair">Sinclair AJ, et al. Essential fatty acid deficiency and evidence for arachidonate synthesis in the cat. Br J Nutr 1981;46:93-93.</ref><ref name="Rivers">Rivers JPW. Essential fatty acids in cats. J Small Anim Prac 1982;23:563-576.</ref><ref>Bauer JE. Fatty acid metabolism in domestic cats (Felis catus) and cheetahs (Acononyx jubatus). Proc Nat Soc 1997;56:1013-1024.</ref> and require a dietary source of AA to meet their metabolic needs. The dietary requirement for LA in cats is lower than dogs because LA is not used as a precursor for synthesis of AA.

==2. Why are they Important?==

==Why are they Important?==

Linoleic acid is concentrated in the skin and hair coat of cats and dogs to form the normal water permeable barrier of the epidermis<ref name="Elias">Elias PM, et al. 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>. Arachidonic acid is incorporated into the lipid bilayer of all cell membranes; it serves both as a structural component of cell walls and a precursor to normal inflammatory mediators<ref name="NRC">National Research Council (NRC). Fat and Fatty Acids In Nutrient Requirements for Dogs and Cats. 2006 Washington, DC: National Academies Press p.81-110.</ref>.

Linoleic acid is concentrated in the skin and hair coat of cats and dogs to form the normal water permeable barrier of the epidermis<ref name="Elias">Elias PM, et al. 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>. Arachidonic acid is incorporated into the lipid bilayer of all cell membranes; it serves both as a structural component of cell walls and a precursor to normal inflammatory mediators<ref name="NRC">National Research Council (NRC). Fat and Fatty Acids In Nutrient Requirements for Dogs and Cats. 2006 Washington, DC: National Academies Press p.81-110.</ref>.

Increased intake of LA above the minimal requirement may help improve skin and coat quality in dogs and cats<ref name="Rees">Rees CA, et al. Effects of dietary fatty flaxseed and sunflower seed supplementation on normal canine serum polyunsaturated fatty acids and skin and hair condition scores. Vet Derm 2001;12:111-117.</ref><ref name="Codner">Codner EC and Thatcher CD. The role of nutrition in the management of dermatoses. Semin Vet Med Surg (Sm Anim) 1990;5:167-177.</ref>. Modification of AA intake in relation to specific omega-3 fatty acids has been suggested as an aid in the management of inflammatory condition (such as allergic dermatitis, nephritis, or inflammatory bowel disease) in dogs and cats<ref name="Raphael">Raphael W and Sordillo LM. Dietary Polyunsaturated Fatty Acids and Inflammation: The Role of Phospholipid Biosynthesis. Int J Mol Sci 2013;14:21167-21188.</ref>. Omega-6 and omega-3 fatty acids compete for the same metabolic enzymes; as such the total amount as well as the ratio of omega-6 to omega-3 fatty acids is an important consideration when evaluating dietary balance or when attempting to modify concentrations of these nutrients for health and disease management.

Increased intake of LA above the minimal requirement may help improve skin and coat quality in dogs and cats<ref name="Rees">Rees CA, et al. Effects of dietary fatty flaxseed and sunflower seed supplementation on normal canine serum polyunsaturated fatty acids and skin and hair condition scores. Vet Derm 2001;12:111-117.</ref><ref name="Codner">Codner EC and Thatcher CD. The role of nutrition in the management of dermatoses. Semin Vet Med Surg (Sm Anim) 1990;5:167-177.</ref>. Modification of AA intake in relation to specific omega-3 fatty acids has been suggested as an aid in the management of inflammatory condition (such as allergic dermatitis, nephritis, or inflammatory bowel disease) in dogs and cats<ref name="Raphael">Raphael W and Sordillo LM. Dietary Polyunsaturated Fatty Acids and Inflammation: The Role of Phospholipid Biosynthesis. Int J Mol Sci 2013;14:21167-21188.</ref>. Omega-6 and omega-3 fatty acids compete for the same metabolic enzymes; as such the total amount as well as the ratio of omega-6 to omega-3 fatty acids is an important consideration when evaluating dietary balance or when attempting to modify concentrations of these nutrients for health and disease management.

==3. Roles in the Body==

==Roles in the Body==

'''Skin and Hair Coat:''' Epidermal keratinocytes secrete the LA-enriched phospholipid, ceramide, in both dogs and cats. Ceramide functions to enhance cell cohesion and create an effective water barrier<ref name="Elias"/>. Increased intake of LA above the minimal requirement may improve skin and coat health in dogs and cats<ref name="Rees"/><ref name="Codner"/>.  

'''Skin and Hair Coat:''' Epidermal keratinocytes secrete the LA-enriched phospholipid, ceramide, in both dogs and cats. Ceramide functions to enhance cell cohesion and create an effective water barrier<ref name="Elias"/>. Increased intake of LA above the minimal requirement may improve skin and coat health in dogs and cats<ref name="Rees"/><ref name="Codner"/>.  

'''Reproduction:''' Queens fed AA deficient diets with adequate levels of LA are unable to support normal pregnancy and fetal development<ref name="MacDonald">MacDonald ML, et al. Effects of linoleate and arachidonate deficiency on reproduction and spermatogenesis in the cat. J Nutr 1984;114:719-726.</ref>, while no impact on male fertility and spermatogenesis is seen.

'''Reproduction:''' Queens fed AA deficient diets with adequate levels of LA are unable to support normal pregnancy and fetal development<ref name="MacDonald">MacDonald ML, et al. Effects of linoleate and arachidonate deficiency on reproduction and spermatogenesis in the cat. J Nutr 1984;114:719-726.</ref>, while no impact on male fertility and spermatogenesis is seen.

==4. Consequences of Omega-6 Fatty Acid Deficiency==

==Consequences of Omega-6 Fatty Acid Deficiency==

#'''Growth''': Kittens fed LA deficient diets fail to grow normally and develop course dull hair coats<ref name="Sinclair"/><ref name="Rivers"/>. Puppies fed a LA deficient diet developed coarse, dry hair coats with skin flaking after 2 months<ref>Weise HF, et al. Influence of High and Low Caloric Intakes on Fat Deficiency of Dogs. J Nutr 1962;76:71-81.</ref>.

#'''Growth''': Kittens fed LA deficient diets fail to grow normally and develop course dull hair coats<ref name="Sinclair"/><ref name="Rivers"/>. Puppies fed a LA deficient diet developed coarse, dry hair coats with skin flaking after 2 months<ref>Weise HF, et al. Influence of High and Low Caloric Intakes on Fat Deficiency of Dogs. J Nutr 1962;76:71-81.</ref>.

#'''Maintenance''': When fed a LA deficient diet, increased endogenous production of oleic acid (18:1n-9) occurs<ref>Spector AA. Lipid metabolism: essential fatty acids. In Biochemical and Physiologic Principles of Human Nutrition. First edition. 2000 Philadelphia, PA: WB Sunders p373. </ref>. Oleic acid is incorporated into ceramide in place of the missing LA, but is less effective at maintaining cell cohesion. Thickening of the epidermis and cellular swelling occur, and the thickened more loosely packed keratinocytes slough readily resulting in the clinical appearance of scaling<ref>Hansen AE, et al. Sequence of histological change in skin of dogs in relation to dietary fat. J Nutr 1954;52:541-554.</ref>. The greasy, flaky skin is prone to secondary infection and pyoderma occurs commonly with LA deficiencies<ref name="Codner"/><ref>Hansen AE, et al. Susceptibility to infection manifested by dog on low fat diet. Fed Proc 1948;7:289.</ref>. Interdigital exudation and otitis externa are also sequelae of LA deficiencies in dogs<ref>Hansen AE and Weise HF. Fat in the diet and relation to nutrition of the dog. I. Characteristic appearance and gross changes of animals fed diets with and without fat. Tex Rep Biol Med 1951;9:491-515. </ref>. There are no clinical signs reported with AA deficiency in adult, non-reproductive cats.

#'''Maintenance''': When fed a LA deficient diet, increased endogenous production of oleic acid (18:1n-9) occurs<ref>Spector AA. Lipid metabolism: essential fatty acids. In Biochemical and Physiologic Principles of Human Nutrition. First edition. 2000 Philadelphia, PA: WB Sunders p373. </ref>. Oleic acid is incorporated into ceramide in place of the missing LA, but is less effective at maintaining cell cohesion. Thickening of the epidermis and cellular swelling occur, and the thickened more loosely packed keratinocytes slough readily resulting in the clinical appearance of scaling<ref>Hansen AE, et al. Sequence of histological change in skin of dogs in relation to dietary fat. J Nutr 1954;52:541-554.</ref>. The greasy, flaky skin is prone to secondary infection and pyoderma occurs commonly with LA deficiencies<ref name="Codner"/><ref>Hansen AE, et al. Susceptibility to infection manifested by dog on low fat diet. Fed Proc 1948;7:289.</ref>. Interdigital exudation and otitis externa are also sequelae of LA deficiencies in dogs<ref>Hansen AE and Weise HF. Fat in the diet and relation to nutrition of the dog. I. Characteristic appearance and gross changes of animals fed diets with and without fat. Tex Rep Biol Med 1951;9:491-515. </ref>. There are no clinical signs reported with AA deficiency in adult, non-reproductive cats.

#'''Reproduction''': Linoleic acid deficiency does not appear to impact reproduction in dogs and cats, but AA deficiency in queens does not support normal pregnancy or fetal development<ref name="MacDonald"/>. Queens fed AA deficient diets from weaning will have normal heat cycles and may have a single litter of kitten, but are unable to support further pregnancies.

#'''Reproduction''': Linoleic acid deficiency does not appear to impact reproduction in dogs and cats, but AA deficiency in queens does not support normal pregnancy or fetal development<ref name="MacDonald"/>. Queens fed AA deficient diets from weaning will have normal heat cycles and may have a single litter of kitten, but are unable to support further pregnancies.

==5. Toxicity==

==Toxicity==

There is speculation that increased intake of omega-6 fatty acids with inadequate omega-3 fatty acids intake may promote a pro-inflammatory state<ref name="Raphael"/>, but research evidence to support this is lacking in dogs and cats.  

There is speculation that increased intake of omega-6 fatty acids with inadequate omega-3 fatty acids intake may promote a pro-inflammatory state<ref name="Raphael"/>, but research evidence to support this is lacking in dogs and cats.  

==6. Dietary Sources==

==Dietary Sources==

Depending on what is fed during production, animal fats (associated with muscle meat, organ meat, and eggs) have varying LA concentrations; animal fats are good sources of AA. Seed and seed oils are more consistent sources of LA. Corn, soy and cottonseed oils have the highest concentrations of LA (approximately 50% of the total fat), while other seed oils are must lower such as flaxseed at 12% LA. Many seed oil crops are also being modified for human health concerns and even those with historically higher levels of LA are being modified to produce less LA and more oleic acid or alpha-linolenic acid<ref>Damude HG and Kinney AJ. Enhancing Plant Seed Oils for Human Nutrition. Plant Physiol 2008;147:962-968. </ref>. Sunflower oil is an example of this genetic modification. Sunflower oil naturally contains close to 65% linoleic acid content but new genetically modified strains are high in oleic acid with only 3% linoleic acid<ref>Lacombe S, et al. An insertion of oleate desaturase homologous sequence silences via siRNA the functional gene leading to high oleic acid content in sunflower seed oil. Mol Genet Genomics 2009;281:43-54.</ref>. Commercial pet food companies monitor levels of essential omega-6 fatty acids in source ingredients, but care must be taken when selecting essential fatty acid sources for home-prepared diets.   

Depending on what is fed during production, animal fats (associated with muscle meat, organ meat, and eggs) have varying LA concentrations; animal fats are good sources of AA. Seed and seed oils are more consistent sources of LA. Corn, soy and cottonseed oils have the highest concentrations of LA (approximately 50% of the total fat), while other seed oils are must lower such as flaxseed at 12% LA. Many seed oil crops are also being modified for human health concerns and even those with historically higher levels of LA are being modified to produce less LA and more oleic acid or alpha-linolenic acid<ref>Damude HG and Kinney AJ. Enhancing Plant Seed Oils for Human Nutrition. Plant Physiol 2008;147:962-968. </ref>. Sunflower oil is an example of this genetic modification. Sunflower oil naturally contains close to 65% linoleic acid content but new genetically modified strains are high in oleic acid with only 3% linoleic acid<ref>Lacombe S, et al. An insertion of oleate desaturase homologous sequence silences via siRNA the functional gene leading to high oleic acid content in sunflower seed oil. Mol Genet Genomics 2009;281:43-54.</ref>. Commercial pet food companies monitor levels of essential omega-6 fatty acids in source ingredients, but care must be taken when selecting essential fatty acid sources for home-prepared diets.