Omega-3 fatty acid 22594 226141520 2008-07-17T00:28:10Z 128.143.246.222 punctuation corrections (minor) {{For2|an explanation of ''n'' and numerical nomenclature (such as ''n''−3 or 18:3)|[[Fatty acid#Nomenclature|Nomenclature of fatty acids]]}} {{fats}} '''''n''−3 fatty acids''' (popularly referred to as '''ω−3 fatty acids''' or '''omega-3 fatty acids''') are a family of [[unsaturated fat|unsaturated]] [[fatty acid]]s that have in common a carbon–carbon [[double bond#Bond order|double bond]] in the [[essential fatty acid#Nomenclature and terminology|''n''−3]] position; that is, the third bond from the methyl end of the fatty acid. Important nutritionally essential ''n''−3 fatty acids are: [[α-linolenic acid]] (ALA), [[eicosapentaenoic acid]] (EPA), and [[docosahexaenoic acid]] (DHA). The human body cannot synthesize ''n''−3 fatty acids ''[[de novo synthesis|de novo]]'', but it can form 20- and 22-carbon unsaturated ''n''−3 fatty acids from the eighteen-carbon ''n''−3 fatty acid, α-linolenic acid. These conversions occur competitively with ''n''−6 fatty acids, which are essential closely related chemical analogues that are derived from linoleic acid. Both the ''n''−3 α-linolenic acid and ''n''−6 linoleic acid are [[essential nutrients]] which must be obtained from food. Synthesis of the longer ''n''−3 fatty acids from linolenic acid within the body is competitively slowed by the ''n''−6 analogues. Thus accumulation of long-chain ''n''−3 fatty acids in tissues is more effective when they are obtained directly from food or when competing amounts of ''n''−6 analogs do not greatly exceed the amounts of ''n''−3. == Chemistry == [[Image:ALAnumbering.svg|360px|right|thumb|Chemical structure of alpha-linolenic acid (ALA), an essential ''n''−3 fatty acid, (18:3Δ9c,12c,15c, which means a chain of 18 carbons with 3 double bonds on carbons numbered 9, 12 and 15). Although chemists count from the carbonyl carbon (blue numbering), physiologists count from the ''n'' (ω) carbon (red numbering). Note that from the ''n'' end (diagram right), the first double bond appears as the third carbon-carbon bond (line segment), hence the name "''n''−3". This is explained by the fact that the ''n'' end is almost never changed during physiologic transformations in the human body, as it is more stable energetically, and other carbohydrates compounds can be synthetized from the other carbonyl end, for example in glycrids, or from double bonds in the middle of the chain.]] The term '''''n''−3''' (also called '''ω−3''' or '''omega-3''') signifies that the first [[double bond]] exists as the '''third''' carbon-carbon bond from the terminal [[methyl]] end (''n'') of the [[carbon chain]]. ''n''−3 fatty acids which are important in human nutrition are: α-linolenic acid (18:3, ''n''−3; ALA), eicosapentaenoic acid (20:5, ''n''−3; EPA), and docosahexaenoic acid (22:6, ''n''−3; DHA). These three [[polyunsaturated|polyunsaturates]] have either 3, 5 or 6 double bonds in a carbon chain of 18, 20 or 22 carbon atoms, respectively. All double bonds are in the ''[[cis]]''-configuration, i.e. the two hydrogen atoms are on the same side of the double bond.<!-- as is observed in almost all naturally-produced fatty acids - Tung oil being a notable exception --> Most naturally-produced fatty acids (created or transformed in animalia or plant cells with an even number of carbon in chains) are in ''cis''-configuration where they are more easily transformable. The ''trans''-configuration results in much more stable chains that are very difficult to further break or transform, forming longer chains that aggregate in tissues and lacking the necessary hydrophilic properties. This ''trans''-configuration can be the result of the transformation in alkaline solutions, or of the action of some bacterias that are shortening the carbonic chains. Natural transforms in vegetal or animal cells more rarely affect the last ''n''−3 group itself. However, ''n''−3 compounds are still more fragile than ''n''−6 because the last double bond is geometrically and electrically more exposed, notably in the natural ''cis'' configuration. {{clear}} ===List of ''n''−3 fatty acids=== This table lists several different names for the most common ''n''−3 fatty acids found in nature. {| class="wikitable" ! Common name ! Lipid name ! Chemical name |- | | 16:3 (''n''−3) | ''all''-''cis''-7,10,13-hexadecatrienoic acid |- | [[Alpha-linolenic acid|α-Linolenic acid]] (ALA) | 18:3 (''n''−3) |''all''-''cis''-9,12,15-octadecatrienoic acid |- | [[Stearidonic acid]] (STD) | 18:4 (''n''−3) |''all''-''cis''-6,9,12,15-octadecatetraenoic acid |- | [[Eicosatrienoic acid]] (ETE) | 20:3 (''n''−3) |''all''-''cis''-11,14,17-eicosatrienoic acid |- | [[Eicosatetraenoic acid]] (ETA) | 20:4 (''n''−3) |''all''-''cis''-8,11,14,17-eicosatetraenoic acid |- | [[Eicosapentaenoic acid]] (EPA) | 20:5 (''n''−3) | ''all''-''cis''-5,8,11,14,17-eicosapentaenoic acid |- | [[Docosapentaenoic acid]] (DPA),<br />Clupanodonic acid | 22:5 (''n''−3) | ''all''-''cis''-7,10,13,16,19-docosapentaenoic acid |- | [[Docosahexaenoic acid]] (DHA) | 22:6 (''n''−3) |''all''-''cis''-4,7,10,13,16,19-docosahexaenoic acid |- | [[Tetracosapentaenoic acid]] | 24:5 (''n''−3) |''all''-''cis''-9,12,15,18,21-docosahexaenoic acid |- | [[Tetracosahexaenoic acid]] (Nisinic acid) | 24:6 (''n''−3) | ''all''-''cis''-6,9,12,15,18,21-tetracosenoic acid |- |} ==Biological significances== :''The biological effects of the ''n''−3 are largely mediated by their interactions with the ''n''−6 fatty acids; see [[Essential fatty acid interactions]] for detail.'' A [[1992]] article by [[biochemistry|biochemist]] [[William E.M. Lands]]<ref name=Lands1992>{{cite journal | author = [[William E.M. Lands|Lands, William E.M.]] | year = 1992 | month = May | title = Biochemistry and physiology of ''n''–3 fatty acids | journal = [[FASEB Journal]] | publisher = [[Federation of American Societies for Experimental Biology]] | volume = 6 | issue = 8 | pages = 2530–2536 | url = http://www.fasebj.org/cgi/reprint/6/8/2530/ | pmid = 1592205 | accessdate = 2008-03-21}}</ref> provides an overview of the research into ''n''−3 fatty acids, and is the basis of this section. The 'essential' fatty acids were given their name when researchers found that they were essential to normal growth in young children and animals. (Note that the modern definition of '[[essential fatty acid|essential']] is more strict.) A small amount of ''n''−3 in the diet (~1% of total calories) enabled normal growth, and increasing the amount had little to no additional benefit. Likewise, researchers found that [[omega-6 fatty acid|''n''−6 fatty acids]] (such as [[gamma-linolenic acid|γ-linolenic acid]] and [[arachidonic acid]]) play a similar role in normal growth. However, they also found that ''n''−6 was "better" at supporting [[dermis|dermal]] integrity, [[renal]] function, and [[parturition]]. These preliminary findings led researchers to concentrate their studies on ''n''−6, and it was only in recent decades that ''n''−3 has become of interest. In 1963 it was discovered that the ''n''−6 arachidonic acid was converted by the body into [[inflammation|pro-inflammatory]] agents called [[prostaglandin]]s. By 1979 more of what are now known as [[eicosanoid]]s were discovered: [[thromboxane]]s, [[prostacyclin]]s and the [[leukotriene]]s. The eicosanoids, which have important biological functions, typically have a short active lifetime in the body, starting with synthesis from fatty acids and ending with metabolism by enzymes. However, if the rate of synthesis exceeds the rate of metabolism, the excess eicosanoids may have deleterious effects. Researchers found that ''n''−3 is also converted into eicosanoids, but at a much slower rate. Eicosanoids made from ''n''−3 fats often have opposing functions to those made from ''n''−6 fats (ie, anti-inflammatory rather than inflammatory). If both ''n''−3 and ''n''−6 are present, they will "compete" to be transformed, so the ratio of ''n''−3:''n''−6 directly affects the type of eicosanoids that are produced. This competition was recognized as important when it was found that [[thromboxane]] is a factor in the clumping of [[platelet]]s, which leads to [[thrombosis]]. The [[leukotriene]]s were similarly found to be important in immune/inflammatory-system response, and therefore relevant to [[arthritis]], [[Lupus erythematosus|lupus]], and [[asthma]]. These discoveries led to greater interest in finding ways to control the synthesis of ''n''−6 eicosanoids. The simplest way would be by consuming more ''n''−3 and fewer ''n''−6 fatty acids. ==Health benefits== On [[September 8]], [[2004]], the U.S. [[Food and Drug Administration]] gave "qualified health claim" status to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) ''n''−3 fatty acids, stating that "supportive but not conclusive research shows that consumption of EPA and DHA [''n''−3] fatty acids may reduce the risk of [[coronary heart disease]]."<ref name=fda2004>{{cite press release |publisher=[[Food and Drug Administration|United States Food and Drug Administration]] |date=[[September 8]], [[2004]] |url=http://www.fda.gov/bbs/topics/news/2004/NEW01115.html |title=FDA announces qualified health claims for omega-3 fatty acids |accessdate=2006-07-10 }}</ref> This updated and modified their health risk advice letter of 2001 (see below). People with certain circulatory problems, such as [[varicose veins]], benefit from [[fish oil]]. Fish oil stimulates [[Circulatory system|blood circulation]], increases the breakdown of [[fibrin]], a compound involved in clot and scar formation, and additionally has been shown to reduce [[blood pressure]].<ref name="Morris1993">{{cite journal | author = Morris, Martha C. | coauthors = Sacks, Frank; Rosner, Bernard | year = 1993 | month = August | title = Does fish oil lower blood pressure? A meta-analysis of controlled trials | journal = [[Circulation (journal)|Circulation]] | publisher = [[American Heart Association]] | volume = 88 | issue = 2 | pages = 523–533 | url = http://circ.ahajournals.org/cgi/reprint/88/2/523/ | pmid = 8339414 }}</ref><ref name="Mori1993">{{cite journal | author = Mori, Trevor A. | coauthors = Bao, Danny Q.; Burke, Valerie; Puddey, Ian B.; Beilin, Lawrence J. | journal = Hypertension | publisher = [[American Heart Association]] | year = 1993 | month = August | title = Docosahexaenoic acid but not eicosapentaenoic acid lowers ambulatory blood pressure and heart rate in humans | volume = 34 | issue = 2 | pages = 253–260 | url = http://hyper.ahajournals.org/cgi/reprint/34/2/253/ | pmid = 10454450 }}</ref> There is strong scientific evidence that ''n''−3 fatty acids significantly reduce blood [[triglyceride]] levels<ref name=Harris1997>{{cite journal | author = Harris, William S. | year = 1997 | month = May | title = ''n''−3 fatty acids and serum lipoproteins: human studies | journal = American Journal of Clinical Nutrition | publisher = The American Society for Nutrition | volume = 65 | issue = 5 Supplement | pages = 1645S–1654S | url = http://www.ajcn.org/cgi/reprint/65/5/1645S/ | pmid = 9129504 }}</ref><ref name=Sanders1997>{{cite journal | author = Sanders, T.A.B. | coauthors = Oakley, F.R.; Miller, G.J.; Mitropoulos, K.A.; Crook, D.; Oliver, M.F. | year = 1997 | month = December | title = Influence of ''n''−6 versus ''n''−3 polyunsaturated fatty acids in diets low in saturated fatty acids on plasma lipoproteins and hemostatic factors | journal = Arteriosclerosis, Thrombosis, and Vascular Biology | publisher = [[American Heart Association]] | volume = 17 | issue = 12 | pages = 3449–3460 | url = http://atvb.ahajournals.org/cgi/content/full/17/12/3449 | pmid = 9437192 }}</ref><ref name=Roche1996>{{cite journal | author = Roche, H.M. | coauthors = Gibney, M.J. | year = 1996 | month = September | title = Postprandial triacylglycerolaemia: the effect of low-fat dietary treatment with and without fish oil supplementation | journal = European Journal of Clinical Nutrition | publisher = [[Nature Publishing Group]] | volume = 50 | issue = 9 | pages = 617–624 | url = http://cat.inist.fr/?aModele=afficheN&cpsidt=3232572 | pmid = 8880041 }}</ref><ref name=Davidson2007>{{cite journal | author = Davidson, Michael H. | coauthors = Stein, Evan A.; Bays, Harold E.; Maki, Kevin C.; Doyle, Ralph T.; Shalwitz, Robert A.; Ballantyne, Christie M.; Ginsberg, Henry N. | year = 2007 | month = July | title = Efficacy and tolerability of adding prescription omega-3 fatty acids 4 g/d to Simvastatin 40&nbsp;mg/d in hypertriglyceridemic patients: An 8-week, randomized, double-blind, placebo-controlled study | journal = Clinical Therapeutics | publisher = [[Elsevier]] | volume = 29 | issue = 7 | pages = 1354–1367 | doi = 10.1016/j.clinthera.2007.07.018 | pmid = 17825687 }}</ref> and regular intake reduces the risk of secondary and primary [[Myocardial infarction|heart attack]].<ref name=Bucher2002>{{cite journal | author = Bucher, Heiner C. | coauthors = Hengstler, Peter; Schindler, Christian; Meier, Gabriela | year = 2002 | march = March | title = ''n''−3 polyunsaturated fatty acids in coronary heart disease: a meta-analysis of randomized controlled trials | journal = The American Journal of Medicine | publisher = [[Elsevier]] | volume = 112 | issue = 4 | pages = 298–304 | doi = 10.1016/S0002-9343(01)01114-7 | pmid = 11893369 }}</ref><ref name=Burr1994>{{cite journal | author = Burr, Michael L. | coauthors = Sweetham, P.M.; Fehily, Ann M. | year = 1994 | month = August | title = Diet and reinfarction | journal = European Heart Journal | publisher = [[Oxford University Press]] | volume = 15 | issue = 8 | pages = 1152–1153 | url = http://eurheartj.oxfordjournals.org/cgi/reprint/15/8/1152 | pmid = 7988613 }}</ref><ref name=Willett1993>{{cite journal | author = Willett, Walter C. | coauthors = Stampfer, M.J.; Colditz, G.A.; Speizer, F.E.; Rosner, B.A.; Hennekens, C.H. | year = 1993 | month = March | title = Intake of trans fatty acids and risk of coronary heart disease among women | journal = [[The Lancet]] | publisher = [[Elsevier]] | volume = 341 | issue = 8845 | pages = 581–585 | doi = 10.1016/0140-6736(93)90350-P | pmid = 8094827 }}</ref><ref name=Stone1996>{{cite journal | author = Stone, Neil J. | year = 1996 | month = November | title = Fish consumption, fish oil, lipids, and coronary heart disease | journal = [[Circulation (journal)|Circulation]] | publisher = [[American Heart Association]] | volume = 94 | pages = 2337–2340 | url = http://circ.ahajournals.org/cgi/content/full/94/9/2337 | pmid = 8901708 }}</ref> Some benefits have been reported in conditions such as rheumatoid arthritis<ref name=Fortin1995>{{cite journal | author = Fortin, Paul R. | coauthors = Lew, Robert A.; Liang, Matthew H.; Wright, Elizabeth A.; Beckett, Laurel A.; Chalmers, Thomas C.; Sperling, Richard I. | year = 1995 | month = November | title = Validation of a meta-analysis: The effects of fish oil in rheumatoid arthritis | journal = Journal of Clinical Epidemiology | publisher = [[Elsevier]] | volume = 48 | issue = 11 | pages = 1379–1390 | doi = 10.1016/0895-4356(95)00028-3 | pmid = 7490601 }}</ref><ref name=Kremer1985>{{cite journal | author = Kremer, Joel M. | coauthors = Bigauoette, J.; Michalek, A.V.; Timchalk, M.A.; Lininger, L.; Rynes, R.I.; Huyck, C.; Zieminski, J.; Bartholomew, L.E. | year = 1985 | month = January | title = Effects of manipulation of dietary fatty acids on clinical manifestations of rheumatoid arthritis. | journal = [[The Lancet]] | publisher = [[Elsevier]] | volume = 1 | issue = 8422 | pages = 184–187 | url = http://www.ncbi.nlm.nih.gov/pubmed/2857265 | pmid = 2857265 | doi = 10.1016/S0140-6736(85)92024-0 }}</ref> and cardiac arrhythmias.<ref name=Christensen1995>{{cite journal | author = Christensen, Jeppe H. | coauthors = Gustenhoff, Peter; Ejlersen, Ejler; Jessen, Torben; Korup, Eva; Rasmussen, Klaus; Dyerberg, Jørn; Schmidt, Erik B. | year = 1995 | month = January | title = ''n''−3 fatty acids and ventricular extrasystoles in patients with ventricular tachyarrhythmias | journal = Nutrition Research | publisher = [[Elsevier]] | volume = 15 | issue = 1 | pages = 1–8 | doi = 10.1016/0271-5317(95)91647-U }}</ref><ref name=Christensen1996>{{cite journal | author = Christensen, Jeppe H. | coauthors = Gustenhoff, Peter; Korup, Eva; Aarøe, Jens; Toft, Egon; Møller, Torn; Rasmussen, Klaus; Dyerberg, Jørn; Schmidt, Erik B. | date = 1996-03-16 | title = Effect of fish oil on heart rate variability in survivors of myocardial infarction: a double blind randomised controlled trial. | journal = [[British Medical Journal]] | publisher = [[British Medical Association]] | volume = 312 | issue = 7032 | pages = 677–678 | url = http://www.bmj.com/cgi/content/full/312/7032/677 | pmid = 8597736 }}</ref><ref name=Pignier2007>{{cite journal | author = Pignier, C. | coauthors = Revenaz, C.; Rauly-Lestienne, I.; Cussac, D.; Delhon, A.; Gardette, J.; Le Grand, B. | year = 2007 | month = November | title = Direct protective effects of poly-unsaturated fatty acids, DHA and EPA, against activation of cardiac late sodium current | journal = Basic Research in Cardiology | publisher = Steinkopff Verlag | volume = 102 | issue = 6 | pages = 553–564 | url = http://www.springerlink.com/content/u454873774830225/ | doi = 10.1007/s00395-007-0676-x | pmid = 17891522 }}</ref> There is a promising preliminary evidence that ''n''-3 fatty acids supplementation might be helpful in cases of depression<ref name="Su2003">{{cite journal | last = Su | first = Kuan-Pin | coauthors = Huang, Shih-Yi; Chiub, Chih-Chiang; Shenc, Winston W. | title = Omega-3 fatty acids in major depressive disorder: A preliminary double-blind, placebo-controlled trial | journal = European Neuropsychopharmacology | publisher = Elsevier | volume = 13 | issue = 4 | pages = 267–271 | year = 2003 | month = August | doi = 10.1016/S0924-977X(03)00032-4 | pmid = 12888186 }}</ref><ref>{{cite journal | last = Naliwaiko | first = K. | coauthors = Araújo, R.L.; da Fonseca, R.V.; Castilho, J.C.; Andreatini, R.; Bellissimo, M.I.; Oliveira, B.H.; Martins, E.F.; Curi, R.; Fernandes, L.C.; Ferraz, A.C. | title = Effects of fish oil on the central nervous system: a new potential antidepressant? | journal = Nutritional Neuroscience | publisher = [[Maney Publishing|Maney]] | year = 2004 | month = April | volume = 7 | issue = 2 | pages = 91–99 | url = http://www.ncbi.nlm.nih.gov/pubmed/15279495 | pmid = 15279495 | doi = 10.1080/10284150410001704525 }}</ref> and anxiety.<ref>{{cite journal | last = Green | first = Pnina | coauthors = Hermesh, Haggai; Monselisec, Assaf; Maromb, Sofi; Presburgerb, Gadi; Weizman, Abraham | title = Red cell membrane omega-3 fatty acids are decreased in nondepressed patients with social anxiety disorder | journal = European Neuropsychopharmacology | year = 2006 | month = February | volume = 16 | issue = 2 | pages = 107–113 | doi = 10.1016/j.euroneuro.2005.07.005 | pmid = 16243493 }}</ref><ref>{{cite journal | author = Yehuda S., Rabinovitz S., Mostofsky D.I. | title = Mixture of essential fatty acids lowers test anxiety | journal = Nutritional Neuroscience | publisher = [[Maney Publishing|Maney]] | year = 2005 | month = August | volume = 8 | issue = 4 | pages = 265–267 | pmid = 16491653 | doi = 10.1080/10284150500445795 <!--Retrieved from CrossRef by DOI bot--> }}</ref> Studies report highly significant improvement from ''n''-3 fatty acids supplementation alone and in conjunction with medication.<ref>{{cite journal | last = Nemets | first = Boris | coauthors = Stahl, Ziva; Belmaker, R.H. | title = Addition of omega-3 fatty acid to maintenance medication treatment for recurrent unipolar depressive disorder | journal = American Journal of Psychiatry | publisher = [[American Psychiatric Association]] | year = 2002 | month = March | volume = 159 | issue = 3 | pages = 477–479 | doi = 10.1176/appi.ajp.159.3.477 | pmid = 11870016 }}</ref> Some research suggests that fish oil intake may reduce the risk of ischemic and thrombotic stroke.<ref name="keli1994">{{cite journal | last = Keli | first = S.O. | coauthors = Feskens, E.J.; Kromhout, D. | title = Fish consumption and risk of stroke: The Zutphen Study | journal = Stroke | volume = 25 | issue = 2 | pages = 328–332 | year = 1994 | month = February | pmid = 8303739 }}</ref><ref name="gillum1996">{{cite journal | last = Gillum | first = R.F. | coauthors = Mussolino, M.E.; Madans, J.H. | title = The relationship between fish consumption and stroke incidence: The NHANES I Epidemiologic Follow-up Study (National Health and Nutrition Examination Survey) | journal = Archives of Internal Medicine | volume = 156 | issue = 5 | pages = 537–542 | year = 1996 | month = March | pmid = 8604960 }}</ref><ref name="iso2001">{{cite journal | last = Iso | first = H. | coauthors = Rexrode, K.M.; Stampfer, M.J.; Manson, J.E.; Colditz, G.A.; Speizer, F.E.; Hennekens, C.H.; Willett, W.C. | title = Intake of fish and omega-3 fatty acids and risk of stroke in women | journal = JAMA | volume = 285 | issue = 3 | pages = 304–312 | year = 2001 | month = January | pmid = 11176840 }}</ref> However, very large amounts may actually increase the risk of hemorrhagic stroke (see below). Lower amounts are not related to this risk,<ref name="iso2001"> 3 grams of total EPA/DHA daily are considered safe with no increased risk of bleeding involved<ref>The U.S. Food and Drug Administration classification - GRAS (Generally Recognized as Safe)</ref> and many studies used substantially higher doses without major side effects (for example: 4.4 grams EPA/2.2 grams DHA in 2003 study).<ref name="Su2003"> Several studies report possible anti-cancer effects of ''n''−3 fatty acids (particularly breast, colon and prostate cancer).<ref name="augustsson2003">{{cite journal | last = Augustsson | first = Katarina | coauthors = Michaud, Dominique S.; Rimm, Eric B.; Leitzmann, Michael F.; Stampfer, Meir J.; Willett, Walter C.; Giovannucci, Edward | title = A prospective study of intake of fish and marine fatty acids and prostate cancer | journal = Cancer Epidemiology, Biomarkers & Prevention | volume = 12 | issue = 1 | pages = 64–67 | year = 2003 | month = January | pmid = 12540506 }}</ref><ref name="dedeckere1999">{{cite journal | last = De Deckere | first = E.A. | title = Possible beneficial effect of fish and fish ''n''−3 polyunsaturated fatty acids in breast and colorectal cancer | journal = European Journal of Cancer Prevention | volume = 8 | issue = 3 | pages = 213–221 | year = 1999 | month = July | pmid = 10443950 }}</ref><ref name="caygill1995">{{cite journal | last = Caygill | first = C.P. | coauthors = Hill, M.J. | title = Fish, ''n''−3 fatty acids and human colorectal and breast cancer mortality | journal = European Journal Of Cancer Prevention | volume = 4 | issue = 4 | pages = 329–332 | year = 1995 | month = August | pmid = 7549825 }}</ref> No clear conclusion can be drawn at this time, however. A 2006 report in the [[Journal of the American Medical Association]] concluded that their review of literature covering [[cohort study|cohorts]] from many countries with a wide variety of demographic characteristics demonstrating a link between ''n''−3 fatty acids and [[cancer]] prevention gave mixed results.<ref name="JAMA2006">{{cite journal | author = Catherine H. MacLean, MD, PhD ''et al'' | year = 2006 | month = January | title = Effects of ''n''−3 Fatty Acids on Cancer Risk | journal = Journal of the American Medical Association | volume = 295 | issue = 4 | pages = 403–415 | pmid = 16434631 | url = http://jama.ama-assn.org/cgi/content/short/295/4/403 | accessdate = 2006-07-07 | doi = 10.1001/jama.295.4.403 }}</ref> This is similar to the findings of a review by the [[British Medical Journal]] of studies up to February 2002 that failed to find clear effects of long and shorter chain ''n''−3 fats on total mortality, combined cardiovascular events and cancer.<ref name="BMJ2006">{{cite journal | author = Lee Hooper ''et al'' | year = 2006 | month = April | title = Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review | journal = British Medical Journal | volume = 332 | pages = 752–760 | doi = 10.1136/bmj.38755.366331.2F | url = http://bmj.bmjjournals.com/cgi/reprint_abr/332/7544/752/ | pmid = 16565093 | accessdate = 2006-07-07 }}</ref> In 1999, the [[GISSI]]-Prevenzione Investigators reported in [[the Lancet]], the results of major clinical study in 11,324 patients with a recent myocardial infarction. Treatment 1 gram per day of ''n''−3 fatty acids reduced the occurrence of death, cardiovascular death and sudden cardiac death by 20%, 30% and 45% respectively.<ref>{{cite journal | title = Dietary supplementation with ''n''−3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. | journal = Lancet | year = 1999 | volume = 354 | pages = 447–455 | pmid = 10465168 | doi = 10.1016/S0140-6736(99)07072-5 }}</ref> These beneficial effects were seen already from three months onwards.<ref>{{cite journal | author = Marchioli R. | title = Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the GISSI-Prevenzione. | journal = Circulation | year = 2002 | volume = 105 | pages = 1897–1903 | pmid = 11997274 | doi = 10.1161/01.CIR.0000014682.14181.F2 <!--Retrieved from CrossRef by DOI bot--> }}</ref> In April 2006, a team led by [[Lee Hooper]] at the [[University of East Anglia]] in [[Norwich]], UK, published a review of almost 100 separate studies into ''n''−3 fatty acids, found in abundance in oily fish. It concluded that they do not have a significant protective effect against cardiovascular disease.<ref name="trivedi2006">{{cite news | last = Trivedi | first = Bijal | url = http://www.newscientist.com/channel/health/mg19125701.300-the-good-the-fad-and-the-unhealthy.html | title = The good, the fad, and the unhealthy | work = New Scientist | date = 2006-09-23 | pages = 42–49 }}</ref> This meta-analysis was controversial and stands in stark contrast with two different reviews also performed in 2006 by the [[American Journal of Clinical Nutrition]]<ref name="wang2006">{{cite journal | last = Wang | first = Chenchen | coauthors = Harris, William S.; Chung, Mei; Lichtenstein, Alice H.; Balk, Ethan M.; Kupelnick, Bruce; Jordan, Harmon S.; Lau, Joseph | title = ''n''−3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review | journal = The American Journal of Clinical Nutrition | volume = 84 | issue = 1 | pages = 5–17 | year = 2006 | month = July | pmid = 16825676 }}</ref> and a second [[Journal of the American Medical Association|JAMA]] review<ref name="mozaffarian2006">{{cite journal | last = Mozaffarian | first = Dariush | coauthors = Rimm, Eric B. | title = Fish intake, contaminants, and human health: evaluating the risks and the benefits | journal = JAMA | volume = 296 | issue = 15 | pages = 1885–1899 | year = 2006 | month = October | pmid = 17047219 }}</ref> that both indicated decreases in total mortality and cardiovascular incidents (i.e. [[myocardial infarction]]s) associated with the regular consumption of fish and [[fish oil]] supplements. In addition ''n''−3 has shown to aid in other mental disorders such as aggression and ADHD ([[Attention-deficit hyperactivity disorder]]).<ref name="richardson2005">{{cite journal | last = Richardson | first = Alexandra J. | coauthors = Montgomery, Paul | title = The Oxford-Durham study: a randomized, controlled trial of dietary supplementation with fatty acids in children with developmental coordination disorder | journal = Pediatrics | volume = 115 | issue = 5 | pages = 1360–1366 | year = 2005 | month = May | pmid = 15867048 }}</ref> Several studies published in 2007 have been more positive. In the March 2007 edition of the journal [[Atherosclerosis|''Atherosclerosis'']], 81 [[Japan]]ese men with unhealthy [[blood sugar]] levels were randomly assigned to receive 1800&nbsp;mg daily of eicosapentaenoic acid (EPA - an ''n''−3 essential fatty acid from fish oil) with the other half being a control group. The thickness of the [[carotid arteries]] and certain measures of blood flow were measured before and after supplementation. This went on for approximately two years. A total of 60 patients (30 in the EPA group and 30 in the control group) completed the study. Those given the EPA had a statistically significant decrease in the thickness of the carotid arteries along with improvement in blood flow. The authors indicated that this was the first demonstration that administration of purified EPA improves the thickness of carotid arteries along with improving blood flow in patients with unhealthy blood sugar levels.<ref name="mita2007">{{cite journal | last = Mita | first = Tomoya | coauthors = Watada, Hirotaka; Ogihara, Takeshi; Nomiyama, Takashi; Ogawa, Osamu; Kinoshita, Junichiro; Shimizu, Tomoaki; Hirose, Takahisa; Tanaka, Yasushi; Kawamori, Ryuzo | title = Eicosapentaenoic acid reduces the progression of carotid intima-media thickness in patients with type 2 diabetes | journal = Atherosclerosis | volume = 191 | issue = 1 | pages = 162–167 | year = 2007 | month = March | pmid = 16616147 }}</ref> In another study published in the American Journal of Health System Pharmacy March 2007, patients with high triglycerides and poor coronary artery health were given 4 grams a day of a combination of EPA and DHA along with some monounsaturated fatty acids. Those patients with very unhealthy triglyceride levels (above 500&nbsp;mg/dl) reduced their triglycerides on average 45% and their VLDL [[cholesterol]] by more than 50%. VLDL is a bad type of cholesterol and elevated triglycerides can also be deleterious for cardiovascular health.<ref name="mckenney2007">{{cite journal | last = McKenney | first = James M. | coauthors = Sica, Domenic | title = Prescription omega-3 fatty acids for the treatment of hypertriglyceridemia | journal = American Journal of Health-System Pharmacy | volume = 64 | issue = 6 | pages = 595–605 | year = 2007 | month = March | pmid = 17353568 }}</ref> There was another study published on the benefits of EPA in ''The Lancet'' in March 2007. This study involved over 18,000 patients with unhealthy cholesterol levels. The patients were randomly assigned to receive either 1,800&nbsp;mg a day of EPA with a statin drug or a statin drug alone. The trial went on for a total of five years. It was found at the end of the study those patients in the EPA group had superior cardiovascular function. Non-fatal coronary events were also significantly reduced in the EPA group. The authors concluded that EPA is a promising treatment for prevention of major coronary events, especially non-fatal coronary events.<ref name="yokoyama2007">{{cite journal | last = Yokoyama | first = Mitsuhiro | coauthors = Origasa, Hideki; Matsuzaki, Masunori; Matsuzawa, Yuji; Saito, Yasushi; Ishikawa, Yuichi; Oikawa, Shinichi; Sasaki, Jun; Hishida, Hitoshi; Itakura, Hiroshige; Kita, Toru; Kitabatake, Akira; Nakaya, Noriaki; Sakata, Toshiie; Shimada, Kazuyuki; Shirato, Kunio | title = Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis | journal = Lancet | volume = 369 | issue = 9567 | pages = 1090–1098 | year = 2007 | month = March | pmid = 17398308 }}</ref> Another study regarding fish oil was published in the ''Journal of Nutrition'' in April 2007. Sixty four healthy Danish infants from nine to twelve months of age received either cow's milk or infant formula alone or with fish oil. It was found that those infants supplemented with fish oil had improvement in immune function maturation with no apparent reduction in immune activation.<ref name="damsgaard2007">{{cite journal | last = Damsgaard | first = Camilla T. | coauthors = Lauritzen, Lotte; Kjær, Tanja M.R.; Holm, Puk M.I.; Fruekilde, Maj-Britt; Michaelsen, Kim F.; Frøkiær, Hanne | title = Fish oil supplementation modulates immune function in healthy infants | journal = The Journal of Nutrition | volume = 137 | issue = 4 | pages = 1031–1036 | year = 2007 | month = April | pmid = 17374672 | url = http://jn.nutrition.org/cgi/reprint/137/4/1031 }}</ref> There was yet another study on ''n''−3 fatty acids published in the April 2007 ''Journal of Neuroscience''. A group of mice were genetically modified to develop accumulation of amyloid and tau proteins in the brain similar to that seen in people with poor memory. The mice were divided into four groups with one group receiving a typical American diet (with high ratio of ''n''−6 to ''n''−3 fatty acids being 10 to 1). The other three groups were given food with a balanced 1 to 1 ''n''−6 to ''n''−3 ratio and two additional groups supplemented with DHA plus long chain ''n''−6 fatty acids. After three months of feeding, all the DHA supplemented groups were noted to have a lower accumulation of beta amyloid and tau protein. Some research suggests that these abnormal proteins may contribute to the development of memory loss in later years.<ref name="green2007">{{cite journal | last = Green | first = Kim N. | coauthors = Martinez-Coria, Hilda; Khashwji, Hasan; Hall, Eileen B.; Yurko-Mauro, Karin A.; Ellis, Lorie; LaFerla, Frank M. | title = Dietary docosahexaenoic acid and docosapentaenoic acid ameliorate amyloid-β and tau pathology via a mechanism involving presenilin 1 levels | journal = The Journal of Neuroscience | volume = 27 | issue = 16 | pages = 4385–4395 | year = 2007 | month = April | pmid = 17442823 | doi = 10.1523/JNEUROSCI.0055-07.2007 }}</ref> There is also a study published regarding ''n''−3 supplementation in children with learning and behavioral problems. This study was published in the April 2007 edition of the ''Journal of the Developmental and Behavioral Pediatrics'' (5), where 132 children, between the ages of seven to twelve years old, with poor learning, participated in a randomized, placebo-controlled, double-blinded interventional trial. A total of 104 children completed the trial. For the first fifteen weeks of this study, the children were given polyunsaturated fatty acids (''n''−3 and ''n''−6, 3000&nbsp;mg a day), polyunsaturated fatty acids plus multi-vitamins and minerals or placebo. After fifteen weeks, all groups crossed over to the polyunsaturated fatty acids (PUFA) plus vitamins and mineral supplement. Parents were asked to rate their children's condition after fifteen and thirty weeks. After thirty weeks, parental ratings of behavior improved significantly in nine out of fourteen scales. The lead author of the study, Dr. Sinn, indicated the present study is the largest PUFA trial to date with children falling in the poor learning and focus range. The results support those of other studies that have found improvement in poor developmental health with essential fatty acid supplementation.<ref name="mckenney2007" /><ref name="yokoyama2007" /><ref name="damsgaard2007" /><ref name="green2007" /><ref name="sinn2007">{{cite journal | last = Sinn | first = Natalie | coauthors = Bryan, Janet | title = Effect of supplementation with polyunsaturated fatty acids and micronutrients on learning and behavior problems associated with child ADHD | journal = Journal of Developmental And Behavioral Pediatrics | volume = 28 | issue = 2 | pages = 82–91 | year = 2007 | month = April | pmid = 17435458 | doi = 10.1097/01.DBP.0000267558.88457.a5 }}</ref><ref name="lee2007">{{cite journal | last = Lee | first = Duk-Hee | coauthors = Lee, In-Kyu; Jin, Soo-Hee; Steffes, Michael; Jacobs, David R. | title = Association between serum concentrations of persistent organic pollutants and insulin resistance among nondiabetic adults: results from the National Health and Nutrition Examination Survey 1999–2002 | journal = Diabetes Care | volume = 30 | issue = 3 | pages = 622–628 | year = 2007 | month = March | pmid = 17327331 }}</ref> Research in 2005 and 2006 has suggested that the in-vitro anti-inflammatory activity of ''n''−3 acids translates into clinical benefits. Cohorts of neck pain patients and of rheumatoid arthritis sufferers have demonstrated benefits comparable to those receiving standard [[NSAID]]s.{{Fact|date=February 2007}} Those who follow a Mediterranean-style diet tend to have less heart disease, higher HDL ("good") cholesterol levels<ref name="kris-etherton2001">{{cite journal | last = Kris-Etherton | first = P. | coauthors = Eckel, R.H.; Howard, B.V.; St Jeor, S.; Bazzarre, T.L. | title = AHA Science Advisory: Lyon Diet Heart Study. Benefits of a Mediterranean-style, National Cholesterol Education Program/American Heart Association Step I dietary pattern on cardiovascular disease | journal = Circulation | volume = 103 | issue = 13 | pages = 1823–1825 | year = 2001 | month = April | pmid = 11282918 }}</ref> and higher proportions of ''n''−3 in tissue highly unsaturated fatty acids.<ref name="lands2003">{{cite journal | last = Lands | first = William E.M. | title = Diets could prevent many diseases | journal = Lipids | volume = 38 | issue = 4 | pages = 317–321 | year = 2003 | month = April | pmid = 12848276 | doi = 10.1007/s11745-003-1066-0 }}</ref> Similar to those who follow a Mediterranean diet, Arctic-dwelling Inuit - who consume high amounts of ''n''−3 fatty acids from fatty fish - also tend to have higher proportions of ''n''−3, increased HDL cholesterol and decreased triglycerides (fatty material that circulates in the blood) and less heart disease. Eating [[walnuts]] (the ratio of ''n''−3 to ''n''−6 is circa 1:4 respectively<ref name="NutritionData-walnuts">{{cite web | url = http://www.nutritiondata.com/facts-C00001-01c20oc.html | title = Nutrition Facts and Analysis for Nuts, Walnuts, English | work = NutritionData }}</ref>) was reported to lower total cholesterol by 4% relative to controls when people also ate 27% less cholesterol.<ref name="zambón2000">{{cite journal | last = Zambón | first = D. | coauthors = Sabaté, J.; Muñoz, S.; Campero, B.; Casals, E.; Merlos, M.; Laguna, J.C.; Ros, E. | title = Substituting walnuts for monounsaturated fat improves the serum lipid profile of hypercholesterolemic men and women: A randomized crossover trial | journal = Annals of Internal Medicine | volume = 132 | issue = 7 | pages = 538–546 | year = 2000 | month = April | pmid = 10744590 }}</ref> A study<ref name="bousquet2008">{{cite journal | last = Bousquet | first = M. | coauthors = Saint-Pierre, M.; Julien, C.; Salem, N.; Cicchetti, F.; Calon, F. | title = Beneficial effects of dietary omega-3 polyunsaturated fatty acid on toxin-induced neuronal degeneration in an animal model of Parkinson's disease | journal = The [[Federation of American Societies for Experimental Biology]] Journal | volume = 22 | issue = 4 | pages = 1213–1225 | year = 2008 | month = April | pmid = 18032633 | doi = 10.1096/fj.07-9677com }}</ref> examining whether omega-3 exerts neuroprotective action in Parkinson's disease found that it did, using an experimental model, exhibit a protective effect (much like it did for Alzheimer's disease as well). The scientists exposed mice to either a control or a high omega-3 diet from two to twelve months of age and then treated them with a neurotoxin commonly used as an experimental model for Parkinson's. The scientists found that high doses of omega-3 given to the experimental group completely prevented the neurotoxin-induced decrease of dopamine that ordinarily occurs. Since Parkinson's is a disease caused by disruption of the dopamine system, this protective effect exhibited could show promise for future research in the prevention of Parkinson's disease. A study carried out involving 465 women showed serum levels of [[eicosapentaenoic acid]] is inversely related to the levels of anti-oxidized-[[LDL]] antibodies. Oxidative modification of LDL is thought to play an important role in the development of [[atherosclerosis]].<ref name="garrido-sánchez2008">{{cite journal | last = Garrido-Sánchez | first = L. | coauthors = García-Fuentes, E.; Rojo-Martínez, G.; Cardona, F.; Soriguer, F.; Tinahones, F.J. | title = Inverse relation between levels of anti-oxidized-LDL antibodies and eicosapentanoic acid (EPA) | journal = The British Journal of Nutrition | volume = 22 | issue = | pages = 1–5 | year = 2008 | month = February | pmid = 18252023 | doi = 10.1017/S0007114508921723 }}</ref> In 2008 a German study suggested that Omega-3 fatty acids have a positive effect on [[atopic dermatitis]]<ref>{{cite news | work = Dermatology Times | title = Omega-3 can soothe eczema | url = http://dermatologytimes.modernmedicine.com/dermatologytimes/Research+Briefs/Omega-3-can-soothe-eczema/ArticleStandard/Article/detail/505982?contextCategoryId=44290 | date = 2008-03-27 }}</ref> == Health risks == In a letter published [[October 31]], [[2000]],<ref>{{citation |last=Lewis |first=Christine J. |url=http://www.cfsan.fda.gov/~dms/ds-ltr11.html |title=Letter Regarding Dietary Supplement Health Claim for Omega-3 Fatty Acids and Coronary Heart Disease}}</ref> the United States [[Food and Drug Administration]] Center for Food Safety and Applied Nutrition, Office of Nutritional Products, Labeling, and Dietary Supplements noted that known or suspected risks of EPA and DHA ''n''−3 fatty acids may include the possibility of: * Increased bleeding if overused (normally over 3 grams per day) by a patient who is also taking [[aspirin]] or [[warfarin]]. However, this is disputed.<ref>{{cite web |url=http://www.oilofpisces.com/bloodcoagulation.html |title=Fish Oils and Stroke/Blood Coagulation |work=oilofpisces.com}}</ref> * [[Hemorrhagic stroke]] (only in case of very large doses) <ref name="kromann1980"> {{cite journal | last = Kromann | first = N. | coauthors = Green, A. | title = Epidemiological studies in the Upernavik district, Greenland. Incidence of some chronic diseases 1950-1974 | journal = Acta Medica Scandinavica | volume = 208 | issue = 5 | pages = 401–406 | year = 1980 | pmid = 7457208 }} </ref> * Oxidation of ''n''−3 fatty acids forming biologically active oxidation products. * Reduced glycemic control among diabetics. * Suppression of immune and inflammation responses, and consequently, decreased resistance to infections and increased susceptibility to opportunistic bacteria. * An increase in concentration of LDL cholesterol in some individuals. Subsequent advices from the FDA and national counterparts have permitted health claims associated with heart health. ===Cardiac risk=== Persons with [[congestive heart failure]], chronic recurrent [[angina]] or evidence that their heart is receiving insufficient blood flow are advised to talk to their doctor before taking ''n''−3 fatty acids. It may be prudent for such persons to avoid taking ''n''−3 fatty acids or eating foods that contain them in substantial amounts.<ref name="ornish2006">{{cite news |author = Ornish, Dean |authorlink = Dean Ornish |title = The Dark Side of Good Fats |url = http://www.newsweek.com/id/137192 |work = [[Newsweek]] |page = 2 |date = [[2006-05-02]] |accessdate = 2008-06-14 }}</ref> In congestive heart failure, cells that are only barely receiving enough blood flow become electrically hyperexcitable. This, in turn, can lead to increased risk of irregular heartbeats, which, in turn, can cause sudden cardiac death. ''n''−3 fatty acids seem to stabilize the rhythm of the heart by effectively preventing these hyperexcitable cells from functioning, thereby reducing the likelihood of irregular heartbeats and sudden cardiac death. For most people, this is obviously beneficial and would account for most of the large reduction in the likelihood of sudden cardiac death. Nevertheless, for people with congestive heart failure, the heart is barely pumping blood well enough to keep them alive. In these patients, ''n''−3 fatty acids may eliminate enough of these few pumping cells that the heart would no longer be able to pump sufficient blood to live, causing an increased risk of cardiac death.<ref name="ornish2006"/> ==Research frontiers== ===Developmental differences=== Essential fatty acid supplements have gained popularity for children with [[ADHD]], [[autism]], and other developmental differences.<ref name="levy2005">{{cite journal | last = Levy | first = Susan E. | coauthors = Hyman, Susan L. | title = Novel treatments for autistic spectrum disorders | journal = Mental Retardation and Developmental Disabilities Research Reviews | volume = 11 | issue = 2 | pages = 131–142 | year = 2005 | pmid = 15977319 | doi = 10.1002/mrdd.20062 }}</ref> A 2004 Internet survey found that 29% of surveyed parents used essential fatty acid supplements to treat children with [[autism spectrum disorder]]s.<ref name="green2006">{{cite journal | last = Green | first = Vanessa A. | coauthors = Pituch, Keenan A.; Itchon, Jonathan; Choi, Aram; O'Reilly, Mark; Sigafoos, Jeff | title = Internet survey of treatments used by parents of children with autism | journal = Research in Developmental Disabilities | volume = 27 | issue = 1 | pages = 70–84 | year = 2006 | month = January–February | pmid = 15919178 | doi = 10.1016/j.ridd.2004.12.002 }}</ref> Fish oils appear to reduce ADHD-related symptoms in some children.<ref name="richardson2006">{{cite journal | last = Richardson | first = Alexandra J. | title = Omega-3 fatty acids in ADHD and related neurodevelopmental disorders | journal = International Review of Psychiatry | volume = 18 | issue = 2 | pages = 155–172 | year = 2006 | month = April | pmid = 16777670 | doi = 10.1080/09540260600583031 }}</ref> A 2007 double-blind, placebo-controlled trial of small groups of children found that omega-3 fatty acids reduced hyperactivity in children with [[autism spectrum disorder]]s,<ref name="amminger2007">{{cite journal | last = Amminger | first = Paul G. | coauthors = Berger, Gregor E.; Schäfer, Miriam R.; Klier, Claudia; Friedrich, Max H.; Feucht, Martha | title = Omega-3 fatty acids supplementation in children with autism: a double-blind randomized, placebo-controlled pilot study | journal = Biological Psychiatry | volume = 61 | issue = 4 | pages = 551–553 | year = 2007 | month = Feb | pmid = 16920077 | doi = 10.1016/j.biopsych.2006.05.007 }}</ref> Additional double blind studies have showed "medium to strong treatment effects of omega 3 fatty acids on symptoms of adhd.<ref name="sinn2007" /><ref name="richardson2005">{{cite journal | last = Richardson | first = Alexandra J. | coauthors = Montgomery, Paul | title = The Oxford-Durham study: a randomized, controlled trial of dietary supplementation with fatty acids in children with developmental coordination disorder | journal = Pediatrics | volume = 115 | issue = 5 | pages = 1360–1366 | year = 2005 | month = May | pmid = 15867048 | doi = 10.1542/peds.2004–2164 }}</ref><ref name="myers2007">{{cite journal | last = Myers | first = Scott M. | coauthors = Johnson, Chris Plauché (Council on Children with Disabilities) | title = Management of children with autism spectrum disorders | journal = Pediatrics | volume = 120 | issue = 5 | pages = 1162–1182 | year = 2007 | month = November | pmid = 17967921 | doi = 10.1542/peds.2007-2362 | url = http://pediatrics.aappublications.org/cgi/content/full/120/5/1162 | laysummary = http://www.aap.org/advocacy/releases/oct07autism.htm | laysource = AAP | laydate = 2007-10-29 }}</ref> ===Low birth weight=== In a study of nearly 9,000 pregnant women, researchers found women who ate fish once a week during their first trimester had 3.6 times less risk of low birth weight and premature birth than those who ate no fish. Low consumption of fish was a strong risk factor for preterm delivery and low birth weight.<ref name="olsen2002">{{cite journal | last = Olsen | first = Sjúrður Fróði | coauthors = Secher, Niels Jørgen | title = Low consumption of seafood in early pregnancy as a risk factor for preterm delivery: prospective cohort study | journal = BMJ (Clinical Research Ed.) | volume = 324 | issue = 7335 | pages = 447 | date = [[2002-02-23]] | pmid = 11859044 }}</ref> However, attempts by other groups to reverse this increased risk by encouraging increased pre-natal consumption of fish were unsuccessful.<ref name="odent2002">{{cite journal | last = Odent | first = Michel | coauthors = Colson, Suzanne; De Reu, Paul | title = Consumption of seafood and preterm delivery. Encouraging pregnant women to eat fish did not show effect | journal = BMJ (Clinical Research Ed.) | volume = 324 | issue = 7348 | pages = 1279 | date = [[2002-05-25]] | pmid = 12028992 }}</ref> === Psychiatric disorders === ''n''−3 fatty acids are known to have membrane-enhancing capabilities in brain cells.<ref name="trivedi2006" /> One medical explanation is that ''n''−3 fatty acids play a role in the fortification of the [[myelin|myelin sheaths]]. Not coincidentally, ''n''−3 fatty acids comprise approximately eight percent of the average human brain according to Dr. [[David Horrobin]], a pioneer in fatty acid research. [[Ralph Holman]] of the [[University of Minnesota]], another major researcher in studying essential fatty acids, who gave Omega-3 its name, surmised how ''n''−3 components are analogous to the human brain by stating that "DHA is structure, EPA is function." A benefit of ''n''−3 fatty acids is helping the brain to repair damage by promoting neuronal growth.<ref name="trivedi2006" /> In a six-month study involving people with [[schizophrenia]] and [[Huntington's disease]] who were treated with EPA or a placebo, the placebo group had clearly lost cerebral tissue, while the patients given the supplements had a significant increase of grey and white matter.<ref name="puri2006">{{cite journal | last = Puri | first = Basant K. | title = High-resolution magnetic resonance imaging sinc-interpolation-based subvoxel registration and semi-automated quantitative lateral ventricular morphology employing threshold computation and binary image creation in the study of fatty acid interventions in schizophrenia, depression, chronic fatigue syndrome and Huntington's disease | journal = International Review of Psychiatry | volume = 18 | issue = 2 | pages = 149–154 | year = 2006 | month = April | pmid = 16777669 }}</ref> In the [[prefrontal cortex]] (PFC) of the [[brain]], low brain ''n''−3 fatty acids are thought to lower the dopaminergic [[neurotransmission]] in this brain area, possibly contributing to the negative and neurocognitive symptoms in [[schizophrenia]]. This reduction in [[dopamine]] system function in the PFC may lead to an overactivity in dopaminergic function in the [[limbic system]] of the brain which is suppressively controlled by the PFC dopamine system, causing the positive symptoms of [[schizophrenia]]. This is called the ''n''−3 polyunsaturated fatty acid/dopamine hypothesis of schizophrenia (Ohara, 2007). This mechanism may explain why ''n''−3 supplementation shows effects against both positive, negative and neurocognitive [[symptoms]] in [[schizophrenia]]. Consequently, the past decade of ''n''−3 fatty acid research has procured ''some'' [[Western world|Western]] interest in ''n''−3 fatty acids as being a legitimate 'brain food.' Still, recent claims that one's [[intelligence quotient]], psychological tests measuring certain cognitive skills, including numerical and verbal reasoning skills, are increased on account of ''n''−3 fatty acids consumed by pregnant mothers remain unreliable and controversial. An even more significant focus of research, however, lies in the role of ''n''−3 fatty acids as a non-prescription treatment for certain psychiatric and mental diagnoses and has become a topic of much research and speculation. In 1998, Andrew L. Stoll, MD and his colleagues at [[Harvard University]] conducted a small [[double-blind]] [[placebo]]-controlled study in thirty patients diagnosed with [[bipolar disorder]]. Most subjects in this study were already undergoing psychopharmacological treatment (e.g. 12 out of the 30 were taking lithium). Over the course of four months, he gave 15 subjects capsules containing [[olive oil]], and another 15 subjects capsules containing nine grams of pharmaceutical-quality EPA and DHA. The study showed that subjects in the ''n''−3 group were less likely to experience a relapse of symptoms in the four months of the study. Moreover, the ''n''−3 group experienced significantly more recovery than the placebo group. However, a commentary on the Stoll study notes that the improvement in the ''n''−3 group was too small to be clinically significant.<ref name="calabrese1999">{{cite journal | last = Calabrese | first = J.R. | coauthors = Rapport, D.J.; Shelton, M.D. | title = Fish oils and bipolar disorder: A promising but untested treatment | journal = Archives of General Psychiatry | volume = 56 | issue = 5 | pages = 413–414; discussion 415–416 | year = 1999 | month = May | pmid = 10232295 }}</ref> Though Stoll believes that the 1999 experiment was not as optimal as it could have been and has accordingly pursued further research, the foundation has been laid for more researchers to explore the theoretical association between absorbed ''n''−3 fatty acids and signal transduction inhibition in the brain.<ref name="stoll1999">{{cite journal | last = Stoll | first = A.L. | coauthors = Severus, W.E.; Freeman, M.P.; Rueter, S.; Zboyan, H.A.; Diamond, E.; Cress, K.K.; Marangell, L.B. | title = Omega 3 fatty acids in bipolar disorder: A preliminary double-blind, placebo-controlled trial | journal = Archives of General Psychiatry | volume = 56 | issue = 5 | pages = 407–412 | year = 1999 | month = May | pmid = 10232294 | doi = 10.1001/archpsyc.56.5.407 }}</ref> "Several epidemiological studies suggest covariation between seafood consumption and rates of mood disorders. Biological marker studies indicate deficits in omega−3 fatty acids in people with depressive disorders, while several treatment studies indicate therapeutic benefits from omega-3 supplementation. A similar contribution of omega-3 fatty acids to coronary artery disease may explain the well-described links between coronary artery disease and depression. Deficits in omega-3 fatty acids have been identified as a contributing factor to mood disorders and offer a potential rational treatment approach."<ref name="nemets2006">{{cite journal | last = Nemets | first = Hanah | coauthors = Nemets, Boris; Apter, Alan; Bracha, Ziva; Belmaker, R.H. | title = Omega-3 treatment of childhood depression: A controlled, double-blind pilot study | journal = The American Journal of Psychiatry | volume = 163 | issue = 6 | pages = 1098–1100 | year = 2006 | month = June | pmid = 16741212 }}</ref> In 2004, a study found that 100 suicide attempt patients on average had significantly lower levels of EPA in their blood as compared to controls.<ref name="huan2004">{{cite journal | last = Huan | first = Mingming | coauthors = Hamazaki, Kei; Sun, Yueji; Itomura, Miho; Liu, Hongyan; Kang, Wei; Watanabe, Shiro; Terasawa, Katsutoshi; Hamazaki, Tomohito | title = Suicide attempt and ''n''−3 fatty acid levels in red blood cells: a case control study in China | journal = Biological Psychiatry | volume = 56 | issue = 7 | pages = 490–496 | year = 2004 | month = Oct | pmid = 15450784 | url = http://www.journals.elsevierhealth.com/periodicals/bps/article/PIIS0006322304007061/abstract | doi = 10.1016/j.biopsych.2004.06.028 }}</ref> In 2006, a review of published trials in the American Journal of Clinical Nutrition found that "the evidence available provides little support" for the use of fish or the n–3 long-chain polyunsaturated fatty acids contained in them to improve depressed mood. The study used results of twelve randomized controlled trials in its meta-analysis. The review recommended that "larger trials with adequate power to detect clinically important benefits" be performed.<ref name="appleton2006">{{cite journal | last = Appleton | first = Katherine M. | coauthors = Hayward, Robert C.; Gunnell, David; Peters, Tim J.; Rogers, Peter J.; Kessler, David; Ness, Andrew R. | title = Effects of ''n''−3 long-chain polyunsaturated fatty acids on depressed mood: systematic review of published trials | journal = The American Journal of Clinical Nutrition | volume = 84 | issue = 6 | pages = 1308–1316 | year = 2006 | month = December | pmid = 17158410 | url = http://www.ajcn.org/cgi/content/abstract/84/6/1308 }}</ref> == Dietary sources == === Daily values === As macronutrients, fats are not assigned [[recommended daily allowance]]s. Macronutrients have AI (Acceptable Intake) and AMDR (Acceptable Macronutrient Distribution Range) instead of RDAs. The AI for ''n''−3 is 1.6 grams/day for men and 1.1 grams/day for women<ref name="FNBp423">{{cite book | author = Food and Nutrition Board, Institute of Medicine of the National Academies | authorlink = United States National Academies | title = Dietary Reference Intakes For Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids | pages = 423 | year = 2005 | publisher = The National Academies Press | location = Washington, DC | id = ISBN 0-309-08537-3 | url = http://newton.nap.edu/books/0309085373/html/423.html }}</ref> while the AMDR is 0.6% to 1.2% of total energy.<ref name="FNBp770">{{cite book | author = Food and Nutrition Board, Institute of Medicine of the National Academies | authorlink = United States National Academies | title = Dietary Reference Intakes For Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids | pages = 770 | year = 2005 | publisher = The National Academies Press | location = Washington, DC | id = ISBN 0-309-08537-3 | url = http://newton.nap.edu/books/0309085373/html/770.html }}</ref> "A growing body of literature suggests that higher intakes of α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) may afford some degree of protection against [[coronary heart disease]]. Because the physiological potency of EPA and DHA is much greater than that for α-linolenic acid, it is not possible to estimate one AMDR for all ''n''−3 fatty acids. Approximately 10 percent of the AMDR can be consumed as EPA and/or DHA."<ref name="FNBp770" /> There was insufficient evidence as of 2005 to set a UL (upper tolerable limit) for ''n''−3 fatty acids.<ref name="FNBp423" /> Researchers believe the ideal [[Omega-6 fatty acid|''n''−6]] intake should be no more than 4 to 5 times that of our ''n''−3 intake. The National Institutes of Health recently published recommended daily intakes of fatty acids, specific recommendations include 650&nbsp;mg of EPA and DHA, 2.22 g/day of alpha-linolenic acid and 4.44 g/day of linoleic acid.{{Fact|date=September 2007}} A perceived risk of fish oil ''n''−3 supplementation has been [[heavy metal poisoning]] by the body's accumulation of traces of heavy metals, in particular [[Mercury (element)|mercury]], [[lead]], [[nickel]], [[arsenic]] and [[cadmium]] as well as other contaminants ([[PCBs]], [[furan]]s, [[dioxin]]s), which potentially might be found especially in less-refined fish oil supplements. An independent test in 2006 of 44 fish oils on the US market found that all of the products passed safety standards for potential contaminants.<ref name="CL2005">{{cite web | title = Product Review: Omega-3 Fatty Acids (EPA and DHA) from Fish/Marine Oils | publisher = [[ConsumerLab.com]] | date = 2005-03-15 | url = http://www.consumerlab.com/results/omega3.asp | accessdate = 2007-08-14 }}</ref> The FDA recommends that total dietary intake of ''n''−3 fatty acids from fish not exceed 3 grams per day, of which no more than 2 grams per day are from nutritional supplements.<ref name="fda2004" /> Historically, the [[Council for Responsible Nutrition]] (CRN) and the [[World Health Organization]] (WHO) have published acceptable standards regarding contaminants in fish oil. The most stringent current standard is the [[International Fish Oils Standard]] (IFOS). Fish oils that typically make this highest grade are those that are [[molecular distillation|molecularly distilled]] under vacuum, and have virtually no measurable level of contaminants (measured parts per billion and parts per trillion). ''n''−3 supplementation in food has been a significant recent trend in food fortification, with global food companies launching ''n''−3 fortified bread, mayonnaise, pizza, yogurt, orange juice, children's pasta, milk, eggs, confections and infant formula. ===Fish=== Early humans ate animals that ate grass, which gave those animals a higher Omega-3 profile than today's grain-fed animals. Now, the most widely available source of [[eicosapentaenoic acid|EPA]] and [[docosahexaenoic acid|DHA]] is cold water oily fish such as [[salmon]], [[herring]], [[mackerel]], [[anchovies]] and [[sardine]]s. Oils from these fish have a profile of around seven times as much ''n''−3 as ''n''−6. Other oily fish such as [[tuna]] also contain ''n''−3 in somewhat lesser amounts. Consumers of oily fish should be aware of the potential presence of [[heavy metals]] and fat-soluble pollutants like [[Polychlorinated biphenyl|PCBs]] and [[dioxin]]s which may [[Bioaccumulation|accumulate up the food chain]].<ref>{{cite web |url = http://news.bbc.co.uk/1/hi/health/1911312.stm |title = Pollutants found in fish oil capsules }}</ref> Some supplement manufacturers remove heavy metals and other contaminants from the oil through various means, such as molecular distillation (see above), which increases purity, potency and safety. Even some forms of fish oil may not be optimally digestible. Of four studies that compare bioavailability of the triglyceride form of fish oil vs. the ester form, two have concluded that the natural triglyceride form is better, and the other two studies did not find a significant difference. No studies have shown the ester form to be superior although it is cheaper to manufacture.<ref name="lawson1988">{{cite journal | last = Lawson | first = L.D. | coauthors = Hughes, B.G. | title = Absorption of eicosapentaenoic acid and docosahexaenoic acid from fish oil triacylglycerols or fish oil ethyl esters co-ingested with a high-fat meal | journal = Biochemical and Biophysical Research Communications | volume = 156 | issue = 2 | pages = 960–963 | year = 1988 | month = October | pmid = 2847723 }}</ref><ref name="beckermann1990">{{cite journal | last = Beckermann | first = B. | coauthors = Beneke, M.; Seitz, I. | title = Comparative bioavailability of eicosapentaenoic acid and docasahexaenoic acid from triglycerides, free fatty acids and ethyl esters in volunteers | journal = Arzneimittel-Forschung | volume = 40 | issue = 6 | pages = 700–704 | year = 1990 | month = June | pmid = 2144420 }}</ref> <!--does anyone else want to move this para to talk? it doesn't really add anything conclusive--> <!--I don't. Anyone else?--> Although fish is a dietary source of ''n''−3 fatty acids, fish do not synthesize them; they obtain them from the [[algae]] in their diet.{{Fact|date=April 2008}} ===Flax=== [[Image:Flax seeds.jpg|thumb|250px|[[Flax|Flax seeds]] produce [[linseed oil]], which has a very high ''n''−3 content]] Six times richer than most fish oils in ''n''−3,<ref name="flaxcod">{{cite book | author = Thomas Bartram | year = 1998 | title = Bartram's Encyclopedia of Herbal Medicine | pages = 271 }}</ref> [[Flax|Flax (aka linseed)]] (''Linum usitatissimum'') and its oil are perhaps the most widely available [[botanical]] source of ''n''−3. [[Linseed oil|Flaxseed oil]] consists of ca. 55% ALA (alpha-linolenic acid). Flax, like [[chia]], contains approximately three times as much ''n''−3 as ''n''−6. 15 grams of flaxseed oil provides ca. 8 grams of ALA, which is converted in the body to EPA and then DHA at an efficiency of 2–15% and 2–5%, respectively.<ref name="vegsoc">{{cite web | work = Vegetarian Society | url = http://www.vegsoc.org/info/omega3.html | title = Information Sheet on Omega 3 fats }}</ref><!--controversial!, see talk--> ===Botanical sources of ''n''−3 fatty acids=== '''Table 1.''' ''n''−3 content as the percentage of [[alpha-linolenic acid|ALA]] in the seed oil.<ref name="sofadb">{{cite web | url = http://sofa.bfel.de | title = Seed Oil Fatty Acids - SOFA Database Retrieval }}</ref> {| class="wikitable" border=1 cellspacing=0 cellpadding=1 style="border-collapse:collapse;" !|Common name||Alternate name||[[Linnaean name]]||% ''n''−3 |- |[[Chia seed|Chia]] ||[[chia sage]]||''[[Salvia hispanica]]''||64 |- |[[Kiwifruit]]||[[Chinese gooseberry]]||''[[Actinidia chinensis]]''||62 |- |[[Perilla]]||[[shiso]]||''[[Perilla frutescens]]''||58 |- |[[Flax]]||[[linseed]]||''[[Linum usitatissimum]]''||55 |- |[[Cowberry|Lingonberry]]||[[Cowberry]]||''[[Vaccinium vitis-idaea]]''||49 |- |[[Camelina sativa|Camelina]]||[[Gold-of-pleasure]]||''[[Camelina sativa]]''||36 |- |[[Portulaca|Purslane]]||[[Portulaca]]||''[[Portulaca oleracea]]''||35 |- |[[Rubus occidentalis|Black Raspberry]]|| ||''[[Rubus occidentalis]]''||33 |- |} '''Table 2.''' ''n''−3 content as the percentage of [[alpha-linolenic acid|ALA]] in the whole food.<ref name="uos">{{cite web | last = DeFilippis | first = Andrew P. | coauthors = Laurence S. Sperling | title = Understanding omega-3's | url = http://www.biovita.fi/suomi/pdf/understanding_omega3.pdf | accessdate = 21 October | accessyear = 2007 |format=PDF}}</ref><ref name="ngg">{{cite web | last = Wilkinson | first = Jennifer | title = Nut Grower's Guide: The Complete Handbook for Porducers and Hobbyists | url = http://www.publish.csiro.au/samples/Nut%20Growers%20GuideSample.pdf | accessdate = 21 October | accessyear = 2007 |format=PDF}}</ref> {| class="wikitable" border=1 cellspacing=0 cellpadding=1 style="border-collapse:collapse;" !|Common name||[[Linnaean name]]||% ''n''−3 |- |[[Flaxseed]] ||''[[Linum usitatissimum]]''||18.1 |- |[[Butternuts]] ||''[[Juglans cinerea]]'' ||8.7 |- |[[Walnuts]] ||''[[Juglans regia]]'' ||6.3 |- |[[Pecan]] nuts ||''[[Carya illinoinensis]]'' ||0.6 |- |[[Hazel]] nuts ||''[[Corylus avellana]]'' ||0.1 |} === Eggs === [[Egg (food)|Eggs]] produced by chickens fed a diet of greens and insects produce higher levels of ''n''−3 fatty acids (mostly ALA) than chickens fed corn or soybeans.<ref>{{cite web |url = http://www.medicalnewstoday.com/medicalnews.php?newsid=51575 |title = How Omega-6s Usurped Omega-3s In US Diet }}</ref>In addition to feeding chickens insects and greens, fish oils are added to their diet to increase the amount of fatty acid concentrations in eggs.<ref name="trebunová2007">{{cite journal | last = Trebunová | first = A. | coauthors = Vasko, L.; Svedová, M.; Kasteľ, R.; Tucková, M.; Mach, P. | title = The influence of omega-3 polyunsaturated fatty acids feeding on composition of fatty acids in fatty tissues and eggs of laying hens | journal = Deutsche Tierärztliche Wochenschrift | volume = 114 | issue = 7 | pages = 275–279 | year = 2007 | month = July | pmid = 17724936 }}</ref> === Other sources === [[Krill]], which are small, shrimp-like [[zooplankton]], also contain the ''n''−3 fatty acids EPA and DHA. One advantage of extracting ''n''−3 fatty acids from krill, as opposed to sources higher in the food chain, is that krill contain fewer heavy metals and PCBs harmful to humans.{{Fact|date=March 2007}} However, in comparison to higher animals, they also contain fewer ''n''−3 fatty acids per gram.{{Fact|date=March 2007}} The ''n''−6 to ''n''−3 ratio of [[cattle feeding|grass-fed]] beef is about 2:1, making it a more useful source of ''n''−3 than grain-fed beef, which usually has a ratio of 4:1.<ref>{{cite web |url=http://www.csuchico.edu/agr/grsfdbef/health-benefits/ben-o3-o6.html |title=Omega-3/Omega-6 fatty acid content of Grass Fed Beef }}</ref> Commercially available [[domestic sheep|lamb]] is almost always grass-fed, and subsequently higher in ''n''−3 than other common meat sources.{{Fact|date=February 2007}} [[Milk]] and [[cheese]] from grass-fed cows may also be good sources of ''n''−3. One UK study showed that half a pint of milk provides 10% of the recommended daily intake (RDI) of ALA, while a piece of organic cheese the size of a matchbox may provide up to 88%".<ref>{{cite web |url=http://www.vetscite.org/publish/items/001719/ |title=More Omega 3 in Organic Milk }}</ref> The [[microalgae]] ''Crypthecodinium cohnii'' and ''Schizochytrium'' are rich sources of [[docosahexaenoic acid|DHA]] (22:6 ''n''−3) and can be produced commercially in [[bioreactor]]s. Oil from [[brown algae]] (kelp) is a source of EPA. [[Walnuts]] are one of few nuts that contain appreciable ''n''−3 fat, with approximately a 1:4 ratio of ''n''−3 to ''n''−6.<ref name="NutritionData-walnuts" /> [[Acai]] palm fruit also contains ''n''−3 fatty acids. Omega 3 is also found in softgels in pharmacies and nowadays it is also found in combination with omega 6, omega 9 and shark liver oil <ref>{{cite web |url=http://www.articlesbase.com/supplements-and-vitamins-articles/omega-369-for-weight-management-a-cardiosterol-approach-435636.html |title=Omega 3 Omega 6 Omega 9 for weight management. A Cardiosterol approach by Alta Care Laboratoires }}</ref> == The ''n''−6 to ''n''−3 ratio == {{main|Essential fatty acid interactions}} Clinical studies<ref name="Lands1992"/><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 |pmid=14579680 |id=ISBN 3805576404 |doi=10.1159/000073788 }}</ref><ref name="Okuyama2001">{{cite journal |author=Okuyama H |title=High ''n''−6 to ''n''−3 ratio of dietary fatty acids rather than serum cholesterol as a major risk factor for coronary heart disease. |id=''Eur J Lipid Sci Technol''. 2001; 103:418–422. |doi=10.1002/1438-9312(200106)103:6<418::AID-EJLT418>3.0.CO;2-# |year=2001 |journal=European Journal of Lipid Science and Technology |volume=103 |pages=418 }}</ref><ref name=pmid_18196988>{{cite journal |author=Griffin BA |title=How relevant is the ratio of dietary ''n''−6 to ''n''−3 polyunsaturated fatty acids to cardiovascular disease risk? Evidence from the OPTILIP study |journal=Curr. Opin. Lipidol. |volume=19 |issue=1 |pages=57–62 |year=2008 |pmid=18196988 |doi=10.1097/MOL.0b013e3282f2e2a8 |doi_brokendate=2008-06-25}}</ref> indicate that the ingested ratio of ''n''−6 to ''n''−3 (especially Linoleic vs Alpha Linolenic) fatty acids is important to maintaining cardiovascular health. Both ''n''−3 and ''n''−6 fatty acids are essential, i.e. humans must consume them in the diet. ''n''−3 and ''n''−6 compete for the same metabolic enzymes, thus the ''n''−6:''n''−3 ratio will significantly influence the ratio of the ensuing eicosanoids (hormones), (e.g. [[prostaglandins]], [[leukotrienes]], [[thromboxanes]] etc.), and will alter the body's metabolic function.<ref>{{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}}</ref> Generally, grass-fed animals accumulate more ''n''−3 than do grain-fed animals which accumulate relatively more ''n''−6. [[Metabolites]] of ''n''−6 are significantly more inflammatory (esp. [[arachidonic acid]]) than those of ''n''−3. This necessitates that ''n''−3 and ''n''−6 be consumed in a ''balanced proportion''; healthy ratios of ''n''−6:''n''−3 range from 1:1 to 4:1.<ref name="tribole2007">Tribole, 2007</ref><ref name="lands2005">Lands, 2005</ref> Studies suggest that the evolutionary human diet, rich in seafood and other sources of ''n''−3, may have provided such a ratio.<ref name="simopoulos2003" /><ref name="simopoulos2000">{{cite journal |author=Simopoulos AP, Leaf A, Salem Jr N |title=Statement on the essentiality of and recommended dietary intakes for ''n''−6 and ''n''−3 fatty acids |id=Prostaglandins, Leukotrienes and Essential Fatty Acids 2000;63:119–121 |pmid=10991764 }}</ref> Typical Western diets provide ratios of between 10:1 and 30:1 - i.e., dramatically skewed toward ''n''−6.<ref>Hibbeln ''et al.'', 2006</ref> Here are the ratios of ''n''−6 to ''n''−3 fatty acids in some common oils: [[canola]] 2:1, [[soybean]] 7:1, [[olive]] 3–13:1, [[sunflower]] (no ''n''−3), [[flax]] 1:3,<ref>Erasmus, Udo, Fats and Oils. 1986. Alive books, Vancouver, ISBN 0-920470-16-5 p. 263 (round-number ratio within ranges given.)</ref> [[cottonseed]] (almost no ''n''−3), [[peanut]] (no ''n''−3), [[grapeseed oil]] (almost no ''n''−3) and [[corn oil]] 46 to 1 ratio of ''n''−6 to ''n''−3.<ref name="NIHefaeducationpage">{{cite web |title=Essential Fats in Food Oils, NIH page |url=http://efaeducation.nih.gov/sig/esstable.html }}</ref> It should be noted that olive, peanut and canola oils consist of approximately 80% [[monounsaturated fatty acid]]s, (i.e. neither ''n''−6 nor ''n''−3) meaning that they contain relatively small amounts of ''n''−3 and ''n''−6 fatty acids. Consequently, the ''n''−6 to ''n''−3 ratios for these oils (i.e. olive, canola and peanut oils) are not as significant as they are for corn, soybean and sunflower oils. == Conversion efficiency of ALA to EPA and DHA == It has been reported that conversion of ALA to EPA and further to DHA in humans is limited, but varies with individuals.<ref name="ceol">{{cite web | title = Conversion Efficiency of ALA to DHA in Humans | url = http://dhaomega3.org/index.php?category=overview&title=Conversion-of-ALA-to-DHA | accessdate = 21 October | accessyear = 2007 }}</ref> Women have higher ALA conversion efficiency than men, probably due to the lower rate of utilization of dietary ALA for beta-oxidation. This suggests that biological engineering of ALA conversion efficiency is possible. In the online book of ''The Benefits of Omega 3 Fatty Acids found in Seal Oil, as Opposed to Fish and Flaxseed Oils'', Dr. Ho listed the several factors that inhibit the ALA conversion,<ref name="cosf">{{cite web | last = Ho | first = Cosmas | title = Comparing Omega 3's from Fish and Flax Seed Oil | url = http://www.omega3sealoil.com/Chapter4_3c.html | accessdate = 21 October | accessyear = 2007 }}</ref> which again indicate that the efficiency of ALA conversion could be adjusted by altering one's dietary habits, such as rebalancing the ratio of ''n''−3 and ''n''−6 fatty acid intake,<ref name="ceol" /><ref name="ea">{{cite web | title = Eicosanoids Abstracts | url = http://www.integratedhealth.com/infoabstract/eicosab.html | accessdate = 21 October | accessyear = 2007 }}</ref> restraining direct alcohol consumptions, and supplementing vitamins and minerals. However, Goyens ''et al.'' argues that it is the absolute amount of ALA, rather than the ratio of ''n''−3 and ''n''−6 fatty acids, which affects the conversion.<ref name="cala">{{cite journal | last = Goyens | first = Petra LL | coauthors = ''et al.'' | title = Conversion of alpha-linolenic acid in humans is influenced by the absolute amounts of alpha-linolenic acid and linoleic acid in the diet and not by their ratio | url = http://www.ajcn.org/cgi/content/abstract/84/1/44 | pmid = 16825680 | accessdate = 21 October | accessyear = 2007 }}</ref> == See also == {{refbegin|3}} * [[List of omega-3 fatty acids|List of ''n''−3 fatty acids]] * [[Omega-6 fatty acid|''n''−6 fatty acid]] * [[Omega-9 fatty acid|''n''−9 fatty acid]] * [[Essential fatty acid]] * [[Essential fatty acid interactions]] * [[Grape seed oil]] * [[Camelina sativa]] * [[Cod liver oil]] * [[Fish oil]] * [[Flax]] * [[Linseed oil]] * [[Chia]] * [[Portulaca oleracea|Purslane]] * [[Resolvins]] * [[Wakame]] {{refend}} ==Notes and references== {{reflist|2}} ===Additional sources=== {{refbegin}} * Robson, A. 2006. "[http://www.nature.com/doifinder/10.1038/4441002d Shellfish view of omega-3 and sustainable fisheries]." Nature 444, 1002. * Robson, A. 2007. "[http://www.cefas.co.uk/publications/shellfishnews/sfn23.pdf Preventing the diseases of civilisation: shellfish, the omega-3:6 balance and human health]." Shellfish News 23, 25–27 * Cunnane SC (2006) "Survival of the fattest: the key to human brain evolution." M S-MEDECINE SCIENCES 22 (6–7): 659–663. * Bell, J.G., et al. 2004. "Essential fatty acids and phospholipase A2 in autistic spectrum disorders." Prostaglandins Leukot.Essent.Fatty Acids 71(4):201–204. * Bartram, Thomas, 1998, Bartram's Encyclopedia of Herbal Medicine, p.271. * Johnson, S.M., and E. Hollander. 2003. "Evidence that eicosapentaenoic acid is effective in treating autism." J Clin Psychiatry 64(7):848–849. * Ohara, K. "The ''n''−3 polyunsaturated fatty acid/dopamine hypothesis of schizophrenia." Prog Neuropsychopharmacol Biol Psychiatry. 2007 Mar 30;31(2):469–474. * Richardson, A.J., and M.A. Ross. 2000. "Fatty acid metabolism in neurodevelopmental disorder: a new perspective on associations between attention-deficit/hyperactivity disorder, dyslexia, dyspraxia and the autistic spectrum." Prostaglandins Leukot.Essent.Fatty Acids 63(1–2):1–9. * Young, G., and J. Conquer. 2005. "Omega-3 fatty acids and neuropsychiatric disorders." Reprod.Nutr.Dev 45(1):1–28. * Hibbeln JR, Nieminen LR, Blasbalg TL, Riggs JA, Lands WE. Healthy intakes of ''n''−3 and ''n''−6 fatty acids: estimations considering worldwide diversity. Am J Clin Nutr. 2006 Jun;83(6 Suppl):1483S–1493S. * Scher, J., and Pillinger, M. "15d-PGJ2: The anti-inflammatory prostaglandin?" Clinical Immunology. 2005 Feb; 114(2):100–109 {{refend}} ==Further reading== {{refbegin}} * Allport, Susan. [http://worldcat.org/search?q=The+Queen+of+Fats%3A+Why+Omega-3s+Were+Removed+from+the+Western+Diet+and+What+We+Can+Do+to+Replace+Them&qt=mozilla-search''The Queen of Fats: Why Omega-3s Were Removed from the Western Diet and What We Can Do to Replace Them'']. University of California Press, September 2006. ISBN 978-0-520-24282-1. * Chow, Ching Kuang. [http://worldcat.org/oclc/25508943&referer=brief_results ''Fatty Acids in Foods and Their Health Implications'']. Routledge Publishing. New York, New York. 2001. *Clover, Charles. [http://worldcat.org/oclc/67383509&referer=brief_results ''The End of the Line: How overfishing is changing the world and what we eat'']. Ebury Press, London 2004. ISBN 0-09-189780-7 * Stoll, Andrew L. [http://worldcat.org/search?q=The+Omega-3+Connection&fq=ap%3AAndrew+L+Stoll&qt=facet_ap%3A''The Omega-3 Connection'']. Simon & Schuster 2001. ISBN 0-684-87138-6, ISBN 0-684-87139-4 (paperback). * [[Udo Erasmus|Erasmus, Udo]]. [http://worldcat.org/search?q=Fats+That+Heal%2C+Fats+That+Kill&qt=mozilla-search ''Fats That Heal, Fats That Kill'']. 3rd ed. Burnaby (BC): Alive Books; 1993. * Boyd, Hillary & Basant, Puri K. [http://worldcat.org/oclc/59305855''The Natural Way to Beat Depression: the groundbreaking discovery of EPA to change your life.''] London. Hodder and Stoughton. 2004. ISBN 0-340-82497-2 * Tribole, Evelyn. [http://worldcat.org/oclc/77520775&referer=brief_results"The Ultimate Omega-3 Diet]" New York. McGraw-Hill. 2007 ISBN 13:978-0-07-146986-9 * Lands, William E.M. "Fish, Omega-3 and Human Health" Champaign. AOCS Press. 2005 ISBN 1-893997-81-2 {{refend}} ==External links== {{portal|Food}} {{refbegin}} <!--no links to sites that sell omega-3--> * [http://www.americanheart.org/presenter.jhtml?identifier=4632 American Heart Assoc "Fish & Omega-3 Fatty Acids"] * [http://www.amdsupport.ca/articles/86/1/Omega-3-Fatty-Acids-and-the-Prevention-of-Macular-Degeneration/Page1.html Omega-3 Prevents Macular Degeneration] * Further topics and latest scientific research: [http://www.dhaomega3.org DHA/EPA Omega-3 Institute] * BBC News report: [http://news.bbc.co.uk/2/hi/health/4325679.stm Oily fish helps cut inflammation], [[March 12]], [[2005]]. * University of Maryland Medical Center, [http://www.umm.edu/altmed/ConsSupplements/Omega3FattyAcidscs.html omega-3 Fatty Acids] * [http://www.durhamtrial.org/ Durham Research: Using Fatty Acids for Enhancing Classroom Achievement] Website for the Durham Schools Trial, a double blind, placebo controlled trial on the effects of fatty acids with children who were under performing in class. Funded by the Durham City Council and Oxford University. Their [http://pediatrics.aappublications.org/cgi/content/abstract/115/5/1360 initial results] (also available on [http://durham.cergis.com/default.aspx?pid=228 durhamtrial.org]) were published in May 2005. * Read criticism of the above mentioned Durham 'trial' by a columnist for the Guardian at [http://www.badscience.net badscience.net] September 2006 * Essential (Omega-3 and Omega-6) Fatty Acids: [http://lpi.oregonstate.edu/infocenter/othernuts/omega3fa/ The Linus Pauling Institute Micronutrient Information Center] * Simopoulos, AP [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12442909&dopt=Abstract The importance of the ratio of omega-6/omega-3 essential fatty acids.] * [http://www.cfsan.fda.gov/~dms/ds-ltr28.html Letter Responding to a Request to Reconsider the Qualified Claim for a Dietary Supplement Health Claim for Omega-3 Fatty Acids and Coronary Heart Disease] * MedlinePlus Herbs and Supplements: [http://www.nlm.nih.gov/medlineplus/druginfo/natural/patient-fishoil.html Omega-3 fatty acids, fish oil, alpha-linolenic acid] * [http://www.telegraph.co.uk/news/main.jhtml;jsessionid=NOC54WM2O44VLQFIQMFCFGGAVCBQYIV0?xml=/news/2007/11/12/ncurves112.xml Another reason why men like curves] ''(Daily Telegraph)'' Omega-3 credited with shaping a woman's figure to be more attractive to men. * [http://www.omega-3-for-your-health.com More Information On Omega 3] Food Sources, Omega 3 Supplements, Omega 3 Benefits and much more. <!--no links to sites that sell omega-3--> {{refend}} {{Lipids}} [[Category:Lipids]] [[Category:Fatty acids|ω]] [[Category:Biologically based therapies]] [[ca:Àcids grassos omega 3]] [[da:Omega-3-fedtsyre]] [[de:Omega-3-Fettsäuren]] [[es:Ácidos grasos omega 3]] [[fr:Oméga-3]] [[it:Omega-3]] [[he:אומגה 3]] [[la:Omega-3]] [[nl:Omega-3 vetzuren]] [[no:Omega-3-fettsyre]] [[pt:Ômega 3]] [[fi:Omega-3-rasvahapot]] [[sv:Omega 3-fettsyra]] [[th:กรดไขมันโอเมกา 3]] [[tr:Omega-3]] [[wa:Omega 3]]