Omega-6 fatty acids

Omega-6/Drug Interactions:

  • AntiasthmaticsAntiasthmatics: The potential role for omega-6 fatty acids in exercise-induced asthma has been the topic of a review (97). Further details are lacking.
  • Antidiabetic agentsAntidiabetic agents: In animal research, pretreatment with linoleic acid and dihomo-gamma-linolenic acid (omega-6 fatty acids) and simultaneous treatment with linoleic acid, gamma-linolenic acid, and dihomo-gamma-linolenic acid did not prevent the development of diabetes mellitus; however, the severity was less (19). Also, arachidonic acid reduced chemically induced diabetes mellitus and restored the antioxidant fatty acid status to a normal range in this animal model (19). In animal research, a diet high in omega-6 fatty acids led to insulin resistance (58).
  • Antihypertensive agentsAntihypertensive agents: In epidemiological research, intakes of omega-6 fatty acids were higher and omega-3 fatty acids were lower in hypertensive men vs. normotensive men (57).
  • Anti-inflammatory agentsAnti-inflammatory agents: In general, omega-6 fatty acids are considered proinflammatory as a group, based on conversion of arachidonic acid to proinflammatory eicosanoids, as reviewed (30). However, based on in vitro research, the omega-6 fatty acid peroxidation metabolite 4-hydroxynonenal (4-HNE) inhibited tumor necrosis factor and interleukin-1 (IL-1)-beta production in human monocytes in response to lipopolysaccharide (25).
  • Antilipemic agentsAntilipemic agents: In animal research, omega-6 fatty acids (derived by incorporating omega-6 fatty acids into coconut triglycerides) decreased plasma and liver total and LDL cholesterol levels and triglycerides vs. unchanged coconut oil (21). In epidemiological research on metabolism of fatty acids in coronary artery disease patients, the percentage of linoleic acid was positively correlated with HDL cholesterol and the ratio of HDL to total cholesterol, and negatively correlated with triglycerides and total cholesterol (119).
  • Antineoplastic agentsAntineoplastic agents: Omega-6 fatty acids potentially have both anticancer and procancer effects. In animal research, oils rich in omega-6 fatty acids reduced tumor growth (120). However, in epidemiological, animal, and in vitro research, omega-6 fatty acids had procancer effects (37; 38; 39; 40; 41; 42; 43; 44; 45; 46; 47; 48; 49; 50; 51; 52; 53).
  • Antiplatelets/anticoagulantsAntiplatelets/anticoagulants: In animal research, increased plasma omega-6 fatty acids were positively associated with the coagulation proteins, factors VII and X (54). In in vitro research, linoleic acid or an oil with a 1:4 ratio of omega-3 to omega-6 had a slight inhibitory effect on platelet aggregation; inhibition was not as pronounced as that seen with omega-3 fatty acids (55).
  • Cardiovascular agentsCardiovascular agents: Omega-6 fatty acid-rich oils are commonly used as the placebo or control in animal and human studies investigating the cardioprotective effects of omega-3 fatty acids, and, as such, they are considered by many to be harmful to the cardiovascular system. However, there is little evidence suggesting that reducing omega-6 intake is associated with reduced inflammation in the body; this information was discussed recently in a science advisory from the American Heart Association Nutrition Subcommittee of the Council on Nutrition, Physical Activity, and Metabolism, the Council on Cardiovascular Nursing, and the Council on Epidemiology and Prevention (79). In depressed patients, omega-6 fatty acids in blood were associated with plasma levels of homocysteine (81), and in Japan, omega-6 status was weakly associated with the number of plaques in the common carotid (82).
  • Clofibric acidClofibric acid: In vivo, concurrent use of clofibric acid and linoleic acid may increase the conversion of linoleic acid to various metabolites (6,9,12-octadecatrienoic acid, 8,11,14-eicosatrienoic acid, and arachidonic acid) and decrease the conversion to 11,14-eicosadienoic acid (121).
  • Drugs used for osteoporosisDrugs used for osteoporosis: In epidemiological research, intake of omega-6 fatty acids was associated with elevated risk of fracture in the elderly (56).
  • Estrogen and progestin combinationsEstrogen and progestin combinations: In animal research, contraceptive steroids reduced the portion of linoleic acid in the bile lecithin (122).
  • GentamicinGentamicin: In animal research, supplementation with sunflower oil failed to reverse gentamicin-induced nephrotoxicity (123).
  • Immunomodulatory agentsImmunomodulatory agents: In patients with Crohn's disease, use of a food supplement containing higher levels of omega-6 fatty acids did not prevent an increase in inflammatory cytokines (124). In animal research, feeding a plant lipid rich in the omega-6 fatty acid gamma linolenic acid resulted in reduced symptoms of experimental autoimmune encephalomyelitis (125).
  • IronIron: In foods, a combination of heme iron and omega-6 fatty acids resulted in the production of 4-hydroxynonenal (HNE), a product of lipid peroxidation (126). In animal research, iron deficiency decreased membrane levels of linoleic acid and increased membrane levels of arachidonic acid (127).
  • Neurologic agentsNeurologic agents: In animal research, plasma omega-6 fatty acids in general, as well as linoleic acid, were significantly correlated with peroneal nerve conduction velocity; lower plasma polyunsaturated fatty acids, omega-6 fatty acids, linoleic acid, the ratio of omega-6 to omega-3, and arachidonic acid levels were significantly associated with a decline in peripheral nerve function with aging (128). In human research, levels of certain omega-6 fatty acids in the plasma were lower in multiple sclerosis patients vs. healthy controls; dietary intakes were similar (7). In kittens, the removal of dietary long-chain omega-6 fatty acids resulted in attenuation of sensitivity of autoreceptor to apomorphine, suggesting the importance of these fatty acids for a normal pattern of dopaminergic function (129).
  • NorepinephrineNorepinephrine: In animal research, chronic norepinephrine resulted in a decrease in omega-6 fatty acids (130).
  • Psychiatric agentsPsychiatric agents: In various epidemiological studies, higher intakes or blood or adipose levels of omega-6 fatty acids have been associated with attention-deficit hyperactivity disorder (ADHD) (59), depressive symptomology and neuroticism (60), and altered depression scale scores (61).
  • TriiodothyronineTriiodothyronine: In human research, triiodothyronine supplementation of thyroid cancer patients resulted in increased relative amounts of linoleic acid and decreased relative amounts of 20:3 omega-6; in plasma, the relative amounts of all other omega-6 fatty acids decreased (131).

    • Omega-6/Herb/Supplement Interactions:

  • Alpha-linolenic acid (omega-3)Alpha-linolenic acid (omega-3): In vitro, the omega-6 fatty acid gamma-linolenic acid repressed the activity of fatty acid synthase, perhaps by a nonspecific cytotoxic effect due to peroxidative mechanisms and/or accumulation of toxic fluxes of the fatty acid synthase substrate malonyl-CoA (132). Alpha-linolenic acid (omega-3) and gamma-linolenic acid had additive effects.
  • AntiasthmaticsAntiasthmatics: The potential role for omega-6 fatty acids in exercise-induced asthma has been the topic of a review (97). Further details are lacking.
  • AntihypertensivesAntihypertensives: In epidemiological research, intakes of omega-6 fatty acids were higher and omega-3 fatty acids were lower in hypertensive men vs. normotensive men (57).
  • Anti-inflammatory herbsAnti-inflammatory herbs: In general, omega-6 fatty acids are considered proinflammatory as a group, based on conversion of arachidonic acid to proinflammatory eicosanoids, as reviewed (30). However, in in vitro research, the omega-6 fatty acid peroxidation metabolite 4-hydroxynonenal (4-HNE) inhibited tumor necrosis factor and IL-1-beta production in human monocytes in response to lipopolysaccharide (25).
  • Antilipemic herbs and supplementsAntilipemic herbs and supplements: In animal research, omega-6 fatty acids (derived by incorporating omega-6 fatty acids into coconut triglycerides) decreased plasma and liver total and LDL cholesterol levels and triglycerides vs. unchanged coconut oil (21). In epidemiological research on metabolism of fatty acids in coronary artery disease patients, the percentage of linoleic acid was positively correlated with HDL cholesterol and the ratio of HDL to total cholesterol, and negatively correlated with triglycerides and total cholesterol (119).
  • AntineoplasticsAntineoplastics: Omega-6 fatty acids potentially have both anti- and procancer effects. In animal research, oils rich in omega-6 fatty acids reduced tumor growth (120). However, in epidemiological, animal, and in vitro research, omega-6 fatty acids had procancer effects (37; 38; 39; 40; 41; 42; 43; 44; 45; 46; 47; 48; 49; 50; 51; 52; 53).
  • Antiplatelets and anticoagulantsAntiplatelets and anticoagulants: In animal research, increased plasma omega-6 fatty acids were positively associated with the coagulation proteins, factors VII and X (54). In in vitro research, linoleic acid or an oil with a 1:4 ratio of omega-3 to omega-6 had a slight inhibitory effect on platelet aggregation; inhibition was not as pronounced as that seen with omega-3 fatty acids (55).
  • Beta-caroteneBeta-carotene: In animal research, beta-carotene supplementation reduced the number of aberrant crypt foci (precancerous clusters of abnormal glands in the colon) in animals fed high levels of omega-6 fatty acids and injected with the carcinogen azoxymethane (133).
  • Cardiovascular herbs and supplementsCardiovascular herbs and supplements: Omega-6 fatty acid-rich oils are commonly used as the placebo or control in animal and human studies investigating the cardioprotective effects of omega-3 fatty acids, and, as such, they are considered by many to be harmful to the cardiovascular system. However, there is little evidence suggesting reducing omega-6 intake is associated with reduced inflammation in the body; this information was discussed recently in a science advisory from the American Heart Association Nutrition Subcommittee of the Council on Nutrition, Physical Activity, and Metabolism, the Council on Cardiovascular Nursing, and the Council on Epidemiology and Prevention (79). In depressed patients, omega-6 fatty acids in blood were associated with plasma levels of homocysteine (81), and in Japan, omega-6 status was weakly associated with the number of plaques in the common carotid (82).
  • Docosahexaenoic acidDocosahexaenoic acid: In in vitro research, arachidonic acid treatment abrogated the inhibitory effects of docosahexaenoic acid (DHA) on induced cell transformation (134).
  • Flaxseed oilFlaxseed oil: In animal research, feeding flaxseed oil decreased muscle omega-6 levels (135).
  • Hypoglycemic herbs and supplementsHypoglycemic herbs and supplements: In animal research, pretreatment with linoleic acid and dihomo-gamma-linolenic acid (omega-6 fatty acids) and simultaneous treatment with linoleic acid, gamma-linolenic acid, and dihomo-gamma-linolenic acid did not prevent the development of diabetes mellitus; however, the severity was less (19). Also, arachidonic acid reduced chemically induced diabetes mellitus and restored the antioxidant fatty acid status to a normal range in this animal model (19). In animal research, a diet high in omega-6 fatty acids led to insulin resistance (58).
  • Immunomodulatory herbs and supplementsImmunomodulatory herbs and supplements: In patients with Crohn's disease, use of a food supplement containing higher levels of omega-6 fatty acids did not prevent an increase in inflammatory cytokines (124). In animal research, feeding a plant lipid rich in the omega-6 fatty acid gamma linolenic acid resulted in reduced symptoms of experimental autoimmune encephalomyelitis (125).
  • IronIron: In foods, a combination of heme iron and omega-6 fatty acids resulted in the production of 4-hydroxynonenal (HNE), a product of lipid peroxidation (126). In animal research, iron deficiency decreased membrane levels of linoleic acid and increased membrane levels of arachidonic acid (127).
  • Neurological agentsNeurological agents: In animal research, plasma omega-6 fatty acids in general, as well as linoleic acid, were significantly correlated with peroneal nerve conduction velocity; lower plasma PUFA, omega-6 fatty acids, linoleic acid, the ratio of omega-6 to omega-3, and arachidonic acid levels were significantly associated with a decline in peripheral nerve function with aging (128). In human study, levels of certain omega-6 fatty acids in the plasma were lower in multiple sclerosis patients vs. healthy controls; dietary intakes were similar (7). In kittens, the removal of dietary long-chain omega-6 fatty acids resulted in attenuation of sensitivity of autoreceptor to apomorphine, suggesting the importance of these fatty acids for a normal pattern of dopaminergic function (129).
  • Omega-3 fatty acids (general)Omega-3 fatty acids (general): The intake ratio of omega-3 to omega-6 might play a role in the effects of these fatty acids. Based on animal research, the ratio of alpha-linolenic acid to linoleic acid may be useful to determine the effects of alpha-linolenic acid on cholesterol and arachidonic acid (136). This ratio has been examined and shown to affect biochemical outcomes in various animal studies (137). Also, supplementation with omega-3 fatty acids has been shown to reduce omega-6 status (blood, muscle) in human, animal, and in vitro research (138; 139; 130; 140; 141; 142; 143; 144; 145; 146; 147; 148; 149; 43; 150; 151; 152; 153; 154; 155; 156); however, when omega-6 was increased in addition to omega-3, omega-6 levels did not decrease, in human research (157). Altering the ratio of omega-3 to omega-6 fatty acids may alter neurogenesis by influencing membrane proteins, cytokines, or neurotrophins (158). Based on reviews, the appropriate combination of omega-3 and omega-6 fatty acids may show additional benefits in the form of protection from depression, schizophrenia, and Alzheimer's disease (27; 28), as well as ADHD (159). In children with developmental coordination disorder, a product containing both omega-6 and omega-3 fatty acids resulted in improvements in reading, spelling, and behavior (160). In human research, supplementation with 2g of eicosapentaenoic acid (omega-3) daily increased red cell membrane levels of arachidonic acid (omega-6) (161). This is not a common finding.
  • Osteoporosis herbs and supplementsOsteoporosis herbs and supplements: In epidemiological research, intake of omega-6 fatty acids was associated with elevated risk of fracture in the elderly (56).
  • Psychiatric agentsPsychiatric agents: In various epidemiological studies, higher intakes or blood or adipose levels of omega-6 fatty acids have been associated with attention-deficit hyperactivity disorder (ADHD) (59), depressive symptomology and neuroticism (60), and altered depression scale scores (61).
  • QuercetinQuercetin: In animal research, quercetin supplementation reduced the number of aberrant crypt foci (precancerous clusters of abnormal glands in the colon) in animals fed high levels of omega-6 fatty acids and injected with the carcinogen azoxymethane (133).
  • Tetradecylthioacetic acidTetradecylthioacetic acid: In animal research, tetradecylthioacetic acid reduced omega-6 fatty acids, mainly arachidonic acid (162).
  • Vitamin AVitamin A: In animal research, vitamin A-deficient animals had decreased linoleic acid and increased 22:5omega-6 fatty acid in liver microsomal membranes (163).
  • Vitamin EVitamin E: In in vitro research, vitamin E decreased lamb testis levels of arachidonic acid and total omega-6 fatty acids (164).

    • Omega-6/Food Interactions:

  • Alpha-linolenic acid (omega-3)-containing foodsAlpha-linolenic acid (omega-3)-containing foods: In vitro, the omega-6 fatty acid gamma-linolenic acid repressed the activity of fatty acid synthase, perhaps by a nonspecific cytotoxic effect due to peroxidative mechanisms and/or accumulation of toxic fluxes of the FAS substrate malonyl-CoA (132). Alpha-linolenic acid (omega-3) and gamma-linolenic acid (GLA) had additive effects.
  • Beef fatBeef fat: In animal research, feeding beef fat reduced omega-6 fatty acids in rat colonocytes (142).
  • Beta-carotene-containing foodsBeta-carotene-containing foods: In animal research, beta-carotene supplementation reduced the number of aberrant crypt foci in animals fed high levels of omega-6 fatty acids and injected with the carcinogen azoxymethane (133).
  • Docosahexaenoic acid (DHA)-containing foods (e.g., fish)Docosahexaenoic acid (DHA)-containing foods (e.g., fish): In in vitro research, the omega-6 fatty acid arachidonic acid treatment abrogated the inhibitory effects of the omega-3 fatty acid docosahexaenoic acid (DHA) on induced cell transformation (134).
  • FishFish: In pregnant women, frequent fish consumption was associated with reduced arachidonic acid levels in erythrocytes (103).
  • Flaxseed oilFlaxseed oil: In animal research, feeding flaxseed oil decreased muscle omega-6 levels (135).
  • Formula dietsFormula diets: In human research, feeding of a very-low-calorie, fat-free defined formula increased serum arachidonic acid levels and did not affect linoleic acid levels (165).
  • Ironcontaining foodsIron-containing foods: In foods, a combination of heme iron and omega-6 fatty acids resulted in the production of 4-hydroxynonenal (HNE), a product of lipid peroxidation (126). In animal research, iron deficiency decreased membrane levels of linoleic acid and increased membrane levels of arachidonic acid (127).
  • Mediterranean dietMediterranean diet: In human study the Mediterranean dietary pattern reduced omega-6 fatty acid status (166).
  • Occidental dietOccidental diet: In human research, the occidental diet (a Western-type diet) resulted in higher levels of omega-6 fatty acids than the Mediterranean diet (167).
  • Omega-3 fats (general)Omega-3 fats (general): The intake ratio of omega-3 to omega-6 might play a role in the effects of these fatty acids. For example, in animal research, the ratio of alpha-linolenic acid to linoleic acid might be important to determine the cholesterol- and arachidonic acid-lowering effect of dietary alpha-linolenic acid (136). This ratio has been examined and shown to affect biochemical outcomes in various animal studies (137). Also, supplementation with omega-3 fatty acids has been shown to reduce omega-6 status (blood, muscle) in human, animal, and in vitro research (138; 139; 130; 140; 141; 142; 143; 144; 145; 146; 147; 148; 149; 43; 150; 151; 152; 153; 154; 155; 156); however, when omega-6 was increased in addition to omega-3, omega-6 levels did not decrease, in human research (157). Altering the ratio of omega-3 to omega-6 fatty acids may alter neurogenesis by influencing membrane proteins, cytokines, and/or neurotrophins (158). Based on reviews, the appropriate combination of omega-3 and omega-6 fatty acids may show additional benefits in the form of protection from depression, schizophrenia, and Alzheimer's disease (27; 28), as well as ADHD (159). In children with developmental coordination disorder, a product containing both omega-6 and omega-3 fatty acids resulted in improvements in reading, spelling, and behavior (160). In human research, supplementation with 2g of eicosapentaenoic acid (omega-3) daily increased red cell membrane levels of arachidonic acid (omega-6) (161). This is not a common finding.
  • Saturated fatSaturated fat: In animal research, the ratio of linoleic acid to saturated fatty acid might be important to determine the cholesterol- and arachidonic acid-lowering effect of dietary alpha-linolenic acid (136). In animal research, a highly saturated fat diet reduced the ratio of linoleic acid to arachidonic acid and caused an overall decrease in omega-6 fatty acids (168).
  • Trans-fatTrans-fat: In animal research, trans-fat intake increased trans-fatty acids and decreased omega-6 fatty acids in heart phospholipids (169).

    • Omega-6/Lab Interactions:

  • Arterial oxygen pressureArterial oxygen pressure: In animal research, omega-6 fatty acids resulted in a decrease in arterial oxygen pressure (PaO2) (170).
  • Blood glucoseBlood glucose: In animal research, pretreatment with linoleic acid and dihomo-gamma-linolenic acid (omega-6 fatty acids) and simultaneous treatment with linoleic acid, gamma-linolenic acid, and dihomo-gamma-linolenic acid did not prevent the development of diabetes mellitus; however, the severity was less (19). Also, arachidonic acid reduced chemically induced diabetes mellitus and restored the antioxidant fatty acid status to a normal range in this animal model (19). In animal research, a diet high in omega-6 fatty acids led to insulin resistance (58).
  • Blood pressureBlood pressure: In epidemiological research, intakes of omega-6 fatty acids were higher and omega-3 fatty acids were lower in hypertensive men vs. normotensive men (57).
  • CholesterolCholesterol: In epidemiological research on metabolism of fatty acids in coronary artery disease patients, the percentage of linoleic acid was positively correlated with HDL cholesterol and the ratio of HDL to total cholesterol, and negatively correlated with triglycerides and total cholesterol (119). In animal research, omega-6 fatty acids (derived by incorporating omega-6 fatty acids into coconut triglycerides) decreased plasma and liver total and LDL cholesterol levels and triglycerides vs. unchanged coconut oil (21).
  • Coagulation proteinsCoagulation proteins: In animal research, increased plasma omega-6 fatty acids were positively associated with the coagulation proteins, factors VII and X (54).
  • CytokinesCytokines: In patients with Crohn's disease, use of a food supplement containing higher levels of omega-6 fatty acids did not prevent an increase in inflammatory cytokines interleukin-1(IL-1)beta, IL-6, interferon-gamma, monocyte chemoattractant protein-1, IL-2, IL-4, IL-5, and IL-10 (124). In animal research, feeding a plant lipid rich in the omega-6 fatty acid gamma-linolenic acid resulted in increases in the production of induced TGF-beta1 (and mRNA) in spleen mononuclear cells but not interferon-gamma, interleukin (IL)-4, or IL-2 production (125).
  • Omega-6 statusOmega-6 status: Supplementation with omega-3 fatty acids has been shown to reduce omega-6 status (blood, muscle) in human, animal, and in vitro research (138; 139; 130; 140; 141; 142; 143; 144; 145; 146; 147; 148; 149; 43; 150; 151; 152; 153; 154; 155; 156); however, when omega-6 was increased in addition to omega-3, omega-6 levels did not decrease, in human research (157). In human research, supplementation with 2g of eicosapentaenoic acid (omega-3) daily increased red cell membrane levels of arachidonic acid (omega-6) (161). This is not a common finding. In preliminary research, supplementation with omega-6 fatty acids increased omega-6 fatty acid status in various cell membranes in humans, animals, and in vitro (171; 172; 173; 174; 175; 112; 176).
  • Platelet aggregationPlatelet aggregation: In vitro, linoleic acid or an oil with a 1:4 ratio of omega-3 to omega-6 had a slight inhibitory effect on platelet aggregation; inhibition was not as pronounced as that seen with omega-3 fatty acids (55).
  • ProstaglandinsProstaglandins: In animal research, the effect of omega-6 fatty acids on PGE2 vs. PGF2-alpha has been examined (177). Further details are lacking.
  • Secondary bile acidsSecondary bile acids: In animal research, diets high in corn oil (mainly omega-6 fatty acids) significantly increased cecal bacterial 7-alpha-dehydroxylase (involved in generation of secondary bile acids) and excretion of deoxycholic and lithocholic acids (68).
  • Thyroid hormonesThyroid hormones: In animal research, changes in omega-6 to saturated fatty acid ratios did not have an effect on thyroid hormone levels in mice (178).
  • TriglyceridesTriglycerides: Omega-6 fatty acids are often used as control in studies investigating the triglyceride-lowering effects of omega-3 fatty acids (179).