n−6 fatty acids (popularly referred to as ω−6 fatty acids or omega-6 fatty acids) are a family of unsaturatedfatty acids which have in common a carbon–carbon double bond in the 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 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.)
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 prostaglandins 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.[1][2][3]
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.[4][5]
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.[6]
Chronic excessive production of n−6 eicosanoids is associated with heart attacks, thrombotic stroke, arrhythmia, arthritis, osteoporosis, inflammation, mood disorders and cancer.[7] Many of the medications used to treat and manage these conditions work by blocking the effects of the potent n−6 fat, arachidonic acid.[8] 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. [9] 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.[10] (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.[11][12] Many of the anti-mania medications used to treat bipolar disorder work by targeting the arachidonic acid cascade in the brain.[13]
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.[14] 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
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 [15]
^ Simopoulos, Artemis P. (October 2002). "The importance of the ratio of omega-6/omega-3 essential fatty acids". Biomedicine & Pharmacotherapy56 (8): 365–379. PMID 12442909.
^ Simopoulos, Artemis P. (September 2003). "Importance of the ratio of omega-6/omega-3 essential fatty acids: evolutionary aspects". World Review of Nutrition and Dietetics92 (Omega-6/Omega-3 Essential Fatty Acid Ratio: The Scientific Evidence): 1–174. Karger. doi:10.1159/000073788. PMID 14579680. ISBN 3805576404.
^ Wada, M. (August 3 2007). "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". J. Biol. Chem.282 (31): 22254–22266. ASBMB.
