Omega-6 fatty acid 681218 225493846 2008-07-14T00:06:03Z AThing 751678 /* Dietary sources */ {{Merge|fatty acid|date=December 2007}} {{For2|an explanation of ''n'' and numerical nomenclature (such as ''n''−6 or 18:2)|[[Fatty acid#Nomenclature|Nomenclature of fatty acids]]}} {{Fats}} [[Image:LAnumbering.png|375px|thumb|The [[chemical structure]] of [[linoleic acid]], a common ''n''−6 fatty acid found in many [[vegetable oil]]s.]] '''''n''−6 fatty acids''' (popularly referred to as '''ω−6 fatty acids''' or '''omega-6 fatty acids''') are a family of [[unsaturated fat|unsaturated]] [[fatty acid]]s which have in common a carbon–carbon [[double bond#Bond order|double bond]] in the [[Fatty acid#Nomenclature|''n''−6]] position; that is, the sixth bond from the end of the fatty acid. The biological effects of the ''n''−6 fatty acids are largely mediated by their conversion to n-6 eicosanoids that bind to diverse receptors found in every tissue of the body. The conversion of tissue arachidonic acid (20:4n-6) to n-6 prostaglandin and n-6 leukotriene hormones provides many targets for pharmaceutical drug development and treatment to diminish excessive n-6 actions in atherosclerosis, asthma, arthritis, vascular disease, thrombosis, immune-inflammatory processes and tumor proliferation. Competitive interactions with the [[omega-3 fatty acid|''n''−3 fatty acids]] affect the relative storage, mobilization, conversion and action of the n-3 and n-6 eicosanoid precursors. (See [[Essential fatty acid interactions]] for more information.) ==Key ''n''−6 fatty acids== [[Linoleic acid]] (18:2, ''n''−6), the shortest-chained ''n''−6 fatty acid, is an [[essential fatty acid]]. [[Arachidonic acid]] (20:4) is a physiologically significant ''n''−6 fatty acid and is the precursor for [[prostaglandin]]s and other physiologically active molecules. ==Negative health effects== Some medical research suggests that excessive levels of ''n''−6 fatty acids, relative to ''n''−3 fatty acids, may increase the probability of a number of diseases and depression.<ref name="Lands2005">{{cite journal | last = Lands | first = William E.M. | title = Dietary fat and health: the evidence and the politics of prevention: careful use of dietary fats can improve life and prevent disease | journal = [[New York Academy of Sciences|Annals of the New York Academy of Sciences]] | publisher = [[Blackwell Publishing|Blackwell]] | volume = 1055 | pages = 179–192 | year = 2005 | month = December | url = http://dx.doi.org/10.1196/annals.1323.028 | pmid = 16387724 | doi = 10.1196/annals.1323.028 }}</ref><ref name=" Hibbeln2006">{{cite journal | last = Hibbeln | first = Joseph R. | coauthros = Nieminen, Levi R.G.; Blasbalg, Tanya L.; Riggs, Jessica A.; and Lands, William E.M. | title = Healthy intakes of ''n''−3 and ''n''−6 fatty acids: estimations considering worldwide diversity | journal = American Journal of Clinical Nutrition | publisher = American Society for Nutrition | volume = 83 | issue = 6, supplement | pages = 1483S–1493S | year = 2006 | month = June | pmid = 16841858 | url = http://www.ajcn.org/cgi/content/full/83/6/S1483 }}</ref><ref name="Okuyama2007">{{cite journal | last = Okuyama | first = Hirohmi | coauthors = Ichikawa, Yuko; Sun, Yueji; Hamazaki, Tomohito; Lands, William E.M. | title = ω3 fatty acids effectively prevent coronary heart disease and other late-onset diseases: the excessive linoleic acid syndrome | journal = World Review of Nutritional Dietetics | publisher = Karger | volume = 96 | issue = Prevention of Coronary Heart Disease | pages = 83–103 | year = 2007 | id = ISBN 3805581793 | url = http://dx.doi.org/10.1159/000097809 | pmid = 17167282 | doi = 10.1159/000097809 }}</ref> Modern Western diets typically have ratios of ''n''−6 to ''n''−3 in excess of 10 to 1, some as high as 30 to 1. The optimal ratio is thought to be 4 to 1 or lower.<ref name="daley2004">{{cite journal | last = Daley | first = C.A. | coauthors = Abbott, A.; Doyle, P.; Nader, G.; and Larson, S. | title = A literature review of the value-added nutrients found in grass-fed beef products | publisher = [[California State University, Chico]] (College of Agriculture) | date = 2004 | url = http://www.csuchico.edu/agr/grassfedbeef/health-benefits/index.html | accessdate = 2008-03-23 }}</ref><ref name="simopoulos2002">{{cite journal | last = Simopoulos | first = Artemis P. | title = The importance of the ratio of omega-6/omega-3 essential fatty acids | journal = Biomedicine & Pharmacotherapy | volume = 56 | issue = 8 | pages = 365–379 | year = 2002 | month = October | pmid = 12442909 }}</ref> Excess ''n''−6 fats interfere with the health benefits of ''n''−3 fats; in part because they compete for the same rate-limiting enzymes. A high proportion of ''n''−6 to ''n''−3 fat in the diet shifts the physiological state in the tissues toward the pathogenesis of many diseases: prothrombotic, proinflammatory and proconstrictive.<ref name="simopoulos2003">{{cite journal | last = Simopoulos | first = Artemis P. | title = Importance of the ratio of omega-6/omega-3 essential fatty acids: evolutionary aspects | journal = World Review of Nutrition and Dietetics | volume = 92 | issue = Omega-6/Omega-3 Essential Fatty Acid Ratio: The Scientific Evidence | pages = 1–174 | year = 2003 | month = September | publisher = Karger | url = | pmid = 14579680 | id = ISBN 3805576404 | doi = 10.1159/000073788 }}</ref> Chronic excessive production of ''n''−6 eicosanoids is associated with heart attacks, thrombotic stroke, arrhythmia, arthritis, osteoporosis, inflammation, mood disorders and cancer.<ref name="Calder2006">{{cite journal | last = Calder | first = Philip C. | title = ''n''−3 polyunsaturated fatty acids, inflammation, and inflammatory diseases | journal = American Journal of Clinical Nutrition | publisher = American Society for Nutrition | volume = 83 | issue = 6, supplement | pages = 1505S–1519S | year = 2006 | month = June | url = http://www.ajcn.org/cgi/content/full/83/6/S1505 | pmid = 16841861 }}</ref> Many of the medications used to treat and manage these conditions work by blocking the effects of the potent ''n''−6 fat, [[arachidonic acid]].<ref name=" Smith2008">{{cite journal | last = Smith | first = William L. | title = Nutritionally essential fatty acids and biologically indispensable cyclooxygenases | journal = [[Trends (journals)|Trends in Biochemical Sciences]] | publisher = [[Elsevier]] | volume = 33 | issue = 1 | pages = 27–37 | year = 2008 | month = January | url = http://dx.doi.org/10.1016/j.tibs.2007.09.013 | pmid = 18155912 | doi = 10.1016/j.tibs.2007.09.013 }}</ref> Many steps in formation and action of n-6 hormones from n-6 arachidonic acid proceed more vigorously than the corresponding competitive steps in formation and action of n-3 hormones from n-3 eicosapentaenoic acid. <ref name=" Wada 2007">{{cite journal | last = Wada | first = M. | title = Enzymes and receptors of prostaglandin pathways with arachidonic acid-derived versus eicosapentaenoic acid-derived substrates and products. Nutritionally essential fatty acids and biologically indispensable cyclooxygenases | journal = [[J. Biol. Chem.]] | publisher = [[ASBMB]] | volume = 282 | issue = 31 | pages = 22254–22266 | year = 2007 | month = August 3 }}</ref> The [[COX-1]] and [[COX-2]] inhibitor medications, used to treat inflammation and pain, work by preventing the [[COX]] enzymes from turning arachidonic acid into inflammatory compounds.<ref name="Cleland2006">{{cite journal | last = Cleland | first = Leslie G. | coauthors = James, Michael J.; Proudman, Susanna M. | title = Fish oil: what the prescriber needs to know | journal = Arthritis Research & Therapy | publisher = BioMed Central | volume = 8 | issue = 1 | pages = 202 | year = 2006 | month = January | url = http://arthritis-research.com/content/8/1/202 | pmid = 16542466 | doi = 10.1186/ar1876 }}</ref> (See [[Cyclooxygenase]] for more information.) The LOX inhibitor medications often used to treat asthma, work by preventing the LOX enzyme from converting [[arachidonic acid]] into the leukotrienes.<ref name="Mickleborough2005">{{cite journal | last = Mickleborough | first = Timothy D. | title = Dietary omega-3 polyunsaturated fatty acid supplementation and airway hyperresponsiveness in asthma | journal = The Journal of Asthma | publisher = [[Informa|Informa Healthcare]] | volume = 42 | issue = 5 | pages = 305–314 | year = 2005 | month = June | url = http://dx.doi.org/10.1081/JAS-200062950 | pmid = 16036405 | doi = 10.1081/JAS-200062950 }}</ref><ref name="Broughton1997">{{cite journal | last = Broughton | first = K. Shane | coauthors = Johnson, Cody S.; Pace, Bobin K.; Liebman, Michael; Kleppinger, Kent M. | title = Reduced asthma symptoms with ''n''−3 fatty acid ingestion are related to 5-series leukotriene production | journal = American Journal of Clinical Nutrition | publisher = American Society for Nutrition | volume = 65 | issue = 4 | pages = 1011–1017 | year = 2005 | month = April | url = http://www.ajcn.org/cgi/reprint/65/4/1011 | pmid = 9094887 }}</ref> Many of the anti-mania medications used to treat bipolar disorder work by targeting the [[arachidonic acid]] cascade in the brain.<ref name="lee2007">{{cite journal | last = Lee | first = H.J. | coauthors = Rao, J.S.; Rapoport, S.I.; Bazinet, R.P. | title = Antimanic therapies target brain arachidonic acid signaling: lessons learned about the regulation of brain fatty acid metabolism | journal = Prostaglandins, Leukotrienes and Essential Fatty Acids | publisher = [[Elsevier]] | volume = 77 | issue = 5 | pages = 239–246 | year = 2007 | month = November | url = http://dx.doi.org/10.1016/j.plefa.2007.10.018 | pmid = 18042366 | doi = 10.1016/j.plefa.2007.10.018}}</ref> ==Dietary Linoleic Acid Requirement== Adding more controversy to the ''n''−6 fat issue is that the dietary requirement for linoleic acid (the key ''n''−6 fatty acid), has been seriously questioned, because of a significant methodology error discovered by University of Toronto scientist, Stephen Cunnane.<ref name=" Cunnane2003">{{cite journal | last = Cunnane | first = Stephen C. | title = Problems with essential fatty acids: time for a new paradigm? | journal = Progress in Lipid Research | volume = 42 | issue = 6 | pages = 544–568 | year = 2003 | month = November | url = http://dx.doi.org/10.1016/S0163-7827(03)00038-9 | doi = 10.1016/S0163-7827(03)00038-9 | pmid = 14559071 }}</ref> Cunnane discovered that the seminal research used to determine the dietary requirement for linoleic acid was based on feeding animals linoleic acid-deficient diets, which were simultaneously deficient in ''n''−3 fats. The ''n''−3 deficiency was not taken into account. The ''n''−6 oils added back systematically to correct the deficiency also contained trace amounts of ''n''−3 fats. Therefore the researchers were inadvertently correcting the ''n''−3 deficiency as well. Ultimately, it took more oil to correct both deficiencies. According to Cunnane, this error overestimates LA requirements by 5 to 15 times. ==Dietary sources== [[Image:Oenothera biennis 20050825 962.jpg|thumb|200px|The evening primrose flower (''O. biennis'') produces an oil containing a high content of [[γ-linolenic acid]], a type of ''n''−6 fatty acid.]] Four major food oils (palm, soybean, rapeseed and sunflower) provide more than 100 million metric tons annually, providing more than 32 million metric tons of n-6 linoleic acid and 4 million metric tons of n-3 alpha-linolenic acid <ref Gunstone, Frank (December 2007) “Oilseed markets: Market update: Palm oil. INFORM (AOCS) 18(12): 835-836. Dietary sources of ''n''−6 fatty acids include:<ref name="wholehealthmd">{{cite web | title = Omega-6 fatty acids | work = WholeHealthMD | url = http://209.196.51.230/ME2/dirmod.asp?sid=17E09E7CFFF640448FFB0B4FC1B7FEF0&nm=Reference+Library&type=AWHN_Supplements&mod=Supplements&mid=&id=BD5CF1DF38044FBFB58C5BFB72B262D1&tier=2 | accessdate = 2008-03-23}}</ref> * [[poultry]] * [[egg (food)|egg]]s * [[cereal]]s * [[whole-grain]] breads * baked goods * [[nut (fruit)|nuts]] * most [[vegetable oil]]s * [[oenothera|evening primrose oil]] * [[borage|borage oil]] * [[blackcurrant|blackcurrant seed oil]] * [[linseed oil|flax/linseed oil]] * [[hemp oil]] * [[soybean oil]] * [[cottonseed oil]] * [[sunflower seed oil]] * [[corn oil]] * [[safflower oil]] * [[pumpkin seeds]] * acai berry ==List of ''n''−6 fatty acids== {| class="wikitable" ! Common name ! Lipid name ! Chemical name |- | [[Linoleic acid]] | 18:2 (''n''−6) | 9,12-octadecadienoic acid |- | [[Gamma-linolenic acid]] | 18:3 (''n''−6) | 6,9,12-octadecatrienoic acid |- | [[Eicosadienoic acid]] | 20:2 (''n''−6) | 11,14-eicosadienoic acid |- | [[Dihomo-gamma-linolenic acid]] | 20:3 (''n''−6) | 8,11,14-eicosatrienoic acid |- | [[Arachidonic acid]] | 20:4 (''n''−6) | 5,8,11,14-eicosatetraenoic acid |- | [[Docosadienoic acid]] | 22:2 (''n''−6) | 13,16-docosadienoic acid |- | [[Docosatetraenoic acid|Adrenic acid]] | 22:4 (''n''−6) | 7,10,13,16-docosatetraenoic acid |- | [[Docosapentaenoic acid]] | 22:5 (''n''−6) | 4,7,10,13,16-docosapentaenoic acid |- | [[Calendic acid]] | 18:3 (''n''−6) | 8E,10E,12Z-octadecatrienoic acid |} ==See also== * [[Essential fatty acid interactions]] * [[Essential nutrients]] * [[Omega-3 fatty acid|''n''−3 fatty acid]] * [[Omega-9 fatty acid|''n''−9 fatty acid]] == References == {{reflist|2}} === Additional sources === {{refbegin}} * {{cite news | first = Steve | last = Tokar | title = Omega-6 fatty acids cause prostate tumor cell growth in culture | url = http://www.medicalnewstoday.com/articles/29976.php | work = Medical News Today | publisher = MediLexicon International | date = [[2005-09-02]] | accessdate = 2008-03-23}} * {{cite news | title = Brain fatty acid levels linked to depression | url = http://www.news-medical.net/?id=10398 | work = News-Medical.Net | publisher = AZoNetwork | date = [[2005-05-25]] | accessdate = 2008-03-23}} * {{cite journal | last = Tribole | first = E.F. | title = Excess Omega-6 Fats Thwart Health Benefits from Omega-3 Fats | journal = [[British Medical Journal]] Rapid Responses to Hooper, ''et. al.'', 2006 | url = http://www.bmj.com/cgi/eletters/332/7544/752#130637 | date = [[2006-03-27]] | accessdate = 2008-03-23}} {{refend}} {{Lipids}} [[Category:Fatty acids|ω]] [[Category:Essential nutrients]] [[da:Omega-6-fedtsyre]] [[de:Omega-6-Fettsäure]] [[es:Ácidos grasos omega 6]] [[fr:Oméga-6]] [[it:Omega 6]] [[pt:Ômega 6]] [[sv:Omega 6-fettsyra]]