2,184
Views
174
CrossRef citations to date
0
Altmetric
Comprehensive Review

A review of recent evidence in human studies of n-3 and n-6 PUFA intake on cardiovascular disease, cancer, and depressive disorders: does the ratio really matter?

, , , , , & show all
Pages 611-622 | Received 10 Mar 2015, Accepted 12 Jul 2015, Published online: 25 Aug 2015

References

  • Allayee H, Baylin A, Hartiala J, Wijesuriya H, Mehrabian M, Lusis AJ, Campos H. 2008. Nutrigenetic association of the 5-lipoxygenase gene with myocardial infarction. Am J Clin Nutr 88:934–940
  • Baek D, Park Y. 2013. Association between erythrocyte n-3 polyunsaturated fatty acids and biomarkers of inflammation and oxidative stress in patients with and without depression. Prostaglandins Leukot Essent Fatty Acids 89:291–296
  • Beydoun MA, Fanelli-Kuczmarski MT, Beydoun HA, Hibbeln JR, Evans MK, Zonderman AB. 2013. Omega-3 fatty acid intakes are inversely related to elevated depressive symptoms among United States women. J Nutr 143:1743–1752
  • Burdge G. 2004. Alpha-linolenic acid metabolism in men and women: nutritional and biological implications. Curr Opin Clin Nutr Metab Care 7:137–144
  • Calder PC. 2010. The American Heart Association advisory on n-6 fatty acids: evidence based or biased evidence? Br J Nutr 104:1575–1576
  • Carayol M, Grosclaude P, Delpierre C. 2010. Prospective studies of dietary alpha-linolenic acid intake and prostate cancer risk: a meta-analysis. Cancer Causes Control 21:347–355
  • Casula M, Soranna D, Catapano AL, Corrao G. 2013. Long-term effect of high dose omega-3 fatty acid supplementation for secondary prevention of cardiovascular outcomes: a meta-analysis of randomized, placebo controlled trials [corrected]. Atheroscler Suppl 14:243–251
  • Chajes V, Torres-Mejia G, Biessy C, Ortega-Olvera C, Angeles-Llerenas A, Ferrari P, Lazcano-Ponce E, Romieu I. 2012. Omega-3 and omega-6 Polyunsaturated fatty acid intakes and the risk of breast cancer in Mexican women: impact of obesity status. Cancer Epidemiol Biomarkers Prev 21:319–326
  • Chapkin RS, Mcmurray DN, Lupton JR. 2007. Colon cancer, fatty acids and anti-inflammatory compounds. Curr Opin Gastroenterol 23:48–54
  • Chowdhury R, Stevens S, Gorman D, Pan A, Warnakula S, Chowdhury S, Ward H, et al. 2012. Association between fish consumption, long chain omega 3 fatty acids, and risk of cerebrovascular disease: systematic review and meta-analysis. BMJ 345:e6698
  • Chowdhury R, Warnakula S, Kunutsor S, Crowe F, Ward HA, Johnson L, Franco OH, et al. 2014. Association of dietary, circulating, and supplement fatty acids with coronary risk: a systematic review and meta-analysis. Ann Intern Med 160:398–406
  • Chua ME, Sio MC, Sorongon MC, Dy JS. 2012. Relationship of dietary intake of omega-3 and omega-6 Fatty acids with risk of prostate cancer development: a meta-analysis of prospective studies and review of literature. Prostate Cancer 2012:826254
  • Corsi L, Dongmo MB, Avallone R. 2015. Supplementation of omega 3 fatty acids improves oxidative stress in activated BV2 microglial cell line. Int J Food Sci Nutr 66:293–299
  • Czernichow S, Thomas D, Bruckert E. 2010. n-6 Fatty acids and cardiovascular health: a review of the evidence for dietary intake recommendations. Br J Nutr 104:788–796
  • Da Rocha CM, Kac G. 2012. High dietary ratio of omega-6 to omega-3 polyunsaturated acids during pregnancy and prevalence of post-partum depression. Matern Child Nutr 8:36–48
  • Daley C, Patterson A, Sibbritt D, Macdonald-Wicks L. 2015. Unsaturated fat intakes and mental health outcomes in young women from the Australian Longitudinal Study on Women’s Health. Public Health Nutr 18:546–553
  • Daniel CR, Mccullough ML, Patel RC, Jacobs EJ, Flanders WD, Thun MJ, Calle EE. 2009. Dietary intake of omega-6 and omega-3 fatty acids and risk of colorectal cancer in a prospective cohort of U.S. men and women. Cancer Epidemiol Biomarkers Prev 18:516–525
  • Das UN. 2008. Essential fatty acids and their metabolites could function as endogenous HMG-CoA reductase and ACE enzyme inhibitors, anti-arrhythmic, anti-hypertensive, anti-atherosclerotic, anti-inflammatory, cytoprotective, and cardioprotective molecules. Lipids Health Dis 7:37
  • Davidson MH. 2006. Mechanisms for the hypotriglyceridemic effect of marine omega-3 fatty acids. Am J Cardiol 98:27i–33i
  • De Goede J, Verschuren WM, Boer JM, Verberne LD, Kromhout D, Geleijnse JM. 2013. N-6 and N-3 fatty acid cholesteryl esters in relation to fatal CHD in a Dutch adult population: a nested case-control study and meta-analysis. PLoS One 8:e59408
  • De Lorgeril M, Renaud S, Mamelle N, Salen P, Martin JL, Monjaud I, Guidollet J, Touboul P, Delaye J. 1994. Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease. Lancet 343:1454–1459
  • Dinan T, Siggins L, Scully P, O’brien S, Ross P, Stanton C. 2009. Investigating the inflammatory phenotype of major depression: focus on cytokines and polyunsaturated fatty acids. J Psychiatr Res 43:471–476
  • Diorio C, Dumas I. 2014. Relations of omega-3 and omega-6 intake with mammographic breast density. Cancer Causes Control 25:339–351
  • Domei T, Yokoi H, Kuramitsu S, Soga Y, Arita T, Ando K, Shirai S, et al. 2012. Ratio of serum n-3 to n-6 polyunsaturated fatty acids and the incidence of major adverse cardiac events in patients undergoing percutaneous coronary intervention. Circ J 76:423–429
  • Duan Y, Li F, Li L, Fan J, Sun X, Yin Y. 2014. n-6:n-3 PUFA ratio is involved in regulating lipid metabolism and inflammation in pigs. Br J Nutr 111:445–451
  • Dwyer JH, Allayee H, Dwyer KM, Fan J, Wu H, Mar R, Lusis AJ, Mehrabian M. 2004. Arachidonate 5-lipoxygenase promoter genotype, dietary arachidonic acid, and atherosclerosis. N Engl J Med 350:29–37
  • EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). 2012. Scientific opinion on the tolerable upper intake level of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA). EFSA J 10:2815
  • Egert S, Stehle P. 2011. Impact of n-3 fatty acids on endothelial function: results from human interventions studies. Curr Opin Clin Nutr Metab Care 14:121–131
  • Estruch R, Ros E, Salas-Salvadó J, Covas MI, Corella D, Arós F, Gómez-Gracia E, et al. 2013. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med 368:1279–1290
  • Evans SJ, Kamali M, Prossin AR, Harrington GJ, Ellingrod VL, Mcinnis MG, Burant CF. 2012. Association of plasma omega-3 and omega-6 lipids with burden of disease measures in bipolar subjects. J Psychiatr Res 46:1435–1441
  • Gao LG, Cao J, Mao QX, Lu XC, Zhou XL, Fan L. 2013. Influence of omega-3 polyunsaturated fatty acid-supplementation on platelet aggregation in humans: a meta-analysis of randomized controlled trials. Atherosclerosis 226:328–334
  • Garcia-Hernandez VM, Gallar M, Sanchez-Soriano J, Micol V, Roche E, Garcia-Garcia E. 2013. Effect of omega-3 dietary supplements with different oxidation levels in the lipidic profile of women: a randomized controlled trial. Int J Food Sci Nutr 64:993–1000
  • GISSI-Prevenzione Investigators. 1999. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico. Lancet 354:447–455
  • Giordano E, Visioli F. 2014. Long-chain omega 3 fatty acids: molecular bases of potential antioxidant actions. Prostaglandins Leukot Essent Fatty Acids 90:1–4
  • Goodstine SL, Zheng T, Holford TR, Ward BA, Carter D, Owens PH, Mayne ST. 2003. Dietary (n-3)/(n-6) fatty acid ratio: possible relationship to premenopausal but not postmenopausal breast cancer risk in U.S. women. J Nutr 133:1409–1414
  • Griffin BA. 2008. How relevant is the ratio of dietary n-6 to n-3 polyunsaturated fatty acids to cardiovascular disease risk? Evidence from the OPTILIP study. Curr Opin Lipidol 19:57–62
  • Grosso G, Buscemi S, Galvano F, Mistretta A, Marventano S, La Vela V, Drago F, et al. 2013. Mediterranean diet and cancer: epidemiological evidence and mechanism of selected aspects. BMC Surg 13:S14
  • Grosso G, Galvano F, Marventano S, Malaguarnera M, Bucolo C, Drago F, Caraci F. 2014a. Omega-3 fatty acids and depression: scientific evidence and biological mechanisms. Oxid Med Cell Longev 2014:313570
  • Grosso G, Mistretta A, Frigiola A, Gruttadauria S, Biondi A, Basile F, Vitaglione P, et al. 2014b. Mediterranean diet and cardiovascular risk factors: a systematic review. Crit Rev Food Sci Nutr 54:593–610
  • Grosso G, Pajak A, Marventano S, Castellano S, Galvano F, Bucolo C, Drago F, Caraci F. 2014c. Role of omega-3 fatty acids in the treatment of depressive disorders: a comprehensive meta-analysis of randomized clinical trials. PLoS One 9:e96905
  • Hamilton JP, Siemer M, Gotlib IH. 2008. Amygdala volume in major depressive disorder: a meta-analysis of magnetic resonance imaging studies. Mol Psychiatry 13:993–1000
  • Harris WS. 2006. The omega-6/omega-3 ratio and cardiovascular disease risk: uses and abuses. Curr Atheroscler Rep 8:453–459
  • Harris WS, Bulchandani D. 2006. Why do omega-3 fatty acids lower serum triglycerides? Curr Opin Lipidol 17:387–393
  • Harris WS, Mozaffarian D, Rimm E, Kris-Etherton P, Rudel LL, Appel LJ, Engler MM, et al. 2009. Omega-6 fatty acids and risk for cardiovascular disease: a science advisory from the American Heart Association Nutrition Subcommittee of the Council on Nutrition, Physical Activity, and Metabolism; Council on Cardiovascular Nursing; and Council on Epidemiology and Prevention. Circulation 119:902–907
  • Hartweg J, Farmer AJ, Holman RR, Neil A. 2009. Potential impact of omega-3 treatment on cardiovascular disease in type 2 diabetes. Curr Opin Lipidol 20:30–38
  • Hartweg J, Farmer AJ, Perera R, Holman RR, Neil HA. 2007. Meta-analysis of the effects of n-3 polyunsaturated fatty acids on lipoproteins and other emerging lipid cardiovascular risk markers in patients with type 2 diabetes. Diabetologia 50:1593–1602
  • Hasegawa T, Otsuka K, Iguchi T, Matsumoto K, Ehara S, Nakata S, Nishimura S, et al. 2014. Serum n-3 to n-6 polyunsaturated fatty acids ratio correlates with coronary plaque vulnerability: an optical coherence tomography study. Heart Vessels 29:596–602
  • Hayakawa S, Yoshikawa D, Ishii H, Tanaka M, Kumagai S, Matsumoto M, Hayashi M, et al. 2012. Association of plasma omega-3 to omega-6 polyunsaturated fatty acid ratio with complexity of coronary artery lesion. Intern Med 51:1009–1014
  • Heerwagen MJ, Stewart MS, De La Houssaye BA, Janssen RC, Friedman JE. 2013. Transgenic increase in N-3/n-6 Fatty Acid ratio reduces maternal obesity-associated inflammation and limits adverse developmental programming in mice. PLoS One 8:e67791
  • Heinze VM, Actis AB. 2012. Dietary conjugated linoleic acid and long-chain n-3 fatty acids in mammary and prostate cancer protection: a review. Int J Food Sci Nutr 63:66–78
  • Hersberger M. 2010. Potential role of the lipoxygenase derived lipid mediators in atherosclerosis: leukotrienes, lipoxins and resolvins. Clin Chem Lab Med 48:1063–1073
  • Hibbeln JR, Salem N Jr. 1995. Dietary polyunsaturated fatty acids and depression: when cholesterol does not satisfy. Am J Clin Nutr 62:1–9
  • Hofmanova J, Strakova N, Vaculova AH, Tylichova Z, Safarikova B, Skender B, Kozubik A. 2014. Interaction of dietary fatty acids with tumour necrosis factor family cytokines during colon inflammation and cancer. Mediators Inflamm 2014:848632
  • Ibiebele TI, Nagle CM, Bain CJ, Webb PM. 2012. Intake of omega-3 and omega-6 fatty acids and risk of ovarian cancer. Cancer Causes Control 23:1775–1783
  • Jadoon A, Chiu CC, Mcdermott L, Cunningham P, Frangou S, Chang CJ, Sun IW, et al. 2012. Associations of polyunsaturated fatty acids with residual depression or anxiety in older people with major depression. J Affect Disord 136:918–925
  • Janakiram NB, Mohammed A, Rao CV. 2011. Role of lipoxins, resolvins, and other bioactive lipids in colon and pancreatic cancer. Cancer Metastasis Rev 30:507–523
  • Johnson GH, Fritsche K. 2012. Effect of dietary linoleic acid on markers of inflammation in healthy persons: a systematic review of randomized controlled trials. J Acad Nutr Diet 112:1029–1041, 1041 e1021–1015
  • Kashiyama T, Ueda Y, Nemoto T, Wada M, Masumura Y, Matsuo K, Nishio M, et al. 2011. Relationship between coronary plaque vulnerability and serum n-3/n-6 polyunsaturated fatty acid ratio. Circ J 75:2432–2438
  • Kesse-Guyot E, Touvier M, Andreeva VA, Jeandel C, Ferry M, Hercberg S, Galan P. 2012. Cross-sectional but not longitudinal association between n-3 fatty acid intake and depressive symptoms: results from the SU.VI.MAX 2 study. Am J Epidemiol 175:979–987
  • Kiecolt-Glaser JK, Belury MA, Porter K, Beversdorf DQ, Lemeshow S, Glaser R. 2007. Depressive symptoms, omega-6:omega-3 fatty acids, and inflammation in older adults. Psychosom Med 69:217–224
  • Larsson SC, Orsini N, Wolk A. 2012. Long-chain omega-3 polyunsaturated fatty acids and risk of stroke: a meta-analysis. Eur J Epidemiol 27:895–901
  • Lev EI, Solodky A, Harel N, Mager A, Brosh D, Assali A, Roller M, et al. 2010. Treatment of aspirin-resistant patients with omega-3 fatty acids versus aspirin dose escalation. J Am Coll Cardiol 55:114–121
  • Lin PY, Huang SY, Su KP. 2010. A meta-analytic review of polyunsaturated fatty acid compositions in patients with depression. Biol Psychiatry 68:140–147
  • Liu HQ, Qiu Y, Mu Y, Zhang XJ, Liu L, Hou XH, Zhang L, et al. 2013. A high ratio of dietary n-3/n-6 polyunsaturated fatty acids improves obesity-linked inflammation and insulin resistance through suppressing activation of TLR4 in SD rats. Nutr Res 33:849–858
  • Lotrich FE, Sears B, Mcnamara RK. 2013. Elevated ratio of arachidonic acid to long-chain omega-3 fatty acids predicts depression development following interferon-alpha treatment: relationship with interleukin-6. Brain Behav Immun 31:48–53
  • Lovegrove JA, Griffin BA. 2013. The acute and long-term effects of dietary fatty acids on vascular function in health and disease. Curr Opin Clin Nutr Metab Care 16:162–167
  • Lucas M, Mirzaei F, O'reilly EJ, Pan A, Willett WC, Kawachi I, Koenen K, Ascherio A. 2011. Dietary intake of n-3 and n-6 fatty acids and the risk of clinical depression in women: a 10-y prospective follow-up study. Am J Clin Nutr 93:1337–1343
  • Makarem N, Chandran U, Bandera EV, Parekh N. 2013. Dietary fat in breast cancer survival. Annu Rev Nutr 33:319–348
  • Mariani J, Doval HC, Nul D, Varini S, Grancelli H, Ferrante D, Tognoni G, Macchia A. 2013. N-3 polyunsaturated fatty acids to prevent atrial fibrillation: updated systematic review and meta-analysis of randomized controlled trials. J Am Heart Assoc 2:e005033
  • Mitchell PL, Mcleod RS. 2008. Conjugated linoleic acid and atherosclerosis: studies in animal models. Biochem Cell Biol 86:293–301
  • Miyake Y, Sasaki S, Yokoyama T, Tanaka K, Ohya Y, Fukushima W, Saito K, et al. 2006. Risk of postpartum depression in relation to dietary fish and fat intake in Japan: the Osaka Maternal and Child Health Study. Psychol Med 36:1727–1735
  • Moore MR, King RA. 2012. Effects of omega-3 fatty acids on progestin stimulation of invasive properties in breast cancer. Horm Cancer 3:205–217
  • Mozaffarian D, Wu JH. 2011. Omega-3 fatty acids and cardiovascular disease: effects on risk factors, molecular pathways, and clinical events. J Am Coll Cardiol 58:2047–2067
  • Mukherjee PK, Chawla A, Loayza MS, Bazan NG. 2007. Docosanoids are multifunctional regulators of neural cell integrity and fate: significance in aging and disease. Prostaglandins Leukot Essent Fatty Acids 77:233–238
  • Myhrstad MC, Retterstol K, Telle-Hansen VH, Ottestad I, Halvorsen B, Holven KB, Ulven SM. 2011. Effect of marine n-3 fatty acids on circulating inflammatory markers in healthy subjects and subjects with cardiovascular risk factors. Inflamm Res 60:309–319
  • Noel SE, Stoneham AC, Olsen CM, Rhodes LE, Green AC. 2014. Consumption of omega-3 fatty acids and the risk of skin cancers: a systematic review and meta-analysis. Int J Cancer 135:149–156
  • Noori N, Dukkipati R, Kovesdy CP, Sim JJ, Feroze U, Murali SB, Bross R, et al. 2011. Dietary omega-3 fatty acid, ratio of omega-6 to omega-3 intake, inflammation, and survival in long-term hemodialysis patients. Am J Kidney Dis 58:248–256
  • Nozue T, Yamamoto S, Tohyama S, Fukui K, Umezawa S, Onishi Y, Kunishima T, et al. 2013a. Comparison of effects of serum n-3 to n-6 polyunsaturated fatty acid ratios on coronary atherosclerosis in patients treated with pitavastatin or pravastatin undergoing percutaneous coronary intervention. Am J Cardiol 111:1570–1575
  • Nozue T, Yamamoto S, Tohyama S, Fukui K, Umezawa S, Onishi Y, Kunishima T, et al. 2013b. Effects of serum n-3 to n-6 polyunsaturated fatty acids ratios on coronary atherosclerosis in statin-treated patients with coronary artery disease. Am J Cardiol 111:6–11
  • Oh DY, Talukdar S, Bae EJ, Imamura T, Morinaga H, Fan W, Li P, et al. 2010. GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell 142:687–698
  • Pan A, Chen M, Chowdhury R, Wu JH, Sun Q, Campos H, Mozaffarian D, Hu FB. 2012. alpha-Linolenic acid and risk of cardiovascular disease: a systematic review and meta-analysis. Am J Clin Nutr 96:1262–1273
  • Pawlosky RJ, Hibbeln JR, Novotny JA, Salem N Jr. 2001. Physiological compartmental analysis of alpha-linolenic acid metabolism in adult humans. J Lipid Res 42:1257–1265
  • Pei J, Zhao Y, Huang L, Zhang X, Wu Y. 2012. The effect of n-3 polyunsaturated fatty acids on plasma lipids and lipoproteins in patients with chronic renal failure – a meta-analysis of randomized controlled trials. J Ren Nutr 22:525–532
  • Peluso I, Romanelli L, Palmery M. 2014. Interactions between prebiotics, probiotics, polyunsaturated fatty acids and polyphenols: diet or supplementation for metabolic syndrome prevention? Int J Food Sci Nutr 65:259–267
  • Psaltopoulou T, Sergentanis TN, Panagiotakos DB, Sergentanis IN, Kosti R, Scarmeas N. 2013. Mediterranean diet, stroke, cognitive impairment, and depression: a meta-analysis. Ann Neurol 74:580–591
  • Ramsden CE, Hibbeln JR, Majchrzak SF, Davis JM. 2010. n-6 fatty acid-specific and mixed polyunsaturate dietary interventions have different effects on CHD risk: a meta-analysis of randomised controlled trials. Br J Nutr 104:1586–1600
  • Ramsden CE, Zamora D, Leelarthaepin B, Majchrzak-Hong SF, Faurot KR, Suchindran CM, Ringel A, et al. 2013. Use of dietary linoleic acid for secondary prevention of coronary heart disease and death: evaluation of recovered data from the Sydney Diet Heart Study and updated meta-analysis. BMJ 346:e8707
  • Rangel-Huerta OD, Aguilera CM, Mesa MD, Gil A. 2012. Omega-3 long-chain polyunsaturated fatty acids supplementation on inflammatory biomakers: a systematic review of randomised clinical trials. Br J Nutr 1072:S159–170
  • Richard D, Bausero P, Schneider C, Visioli F. 2009. Polyunsaturated fatty acids and cardiovascular disease. Cell Mol Life Sci 66:3277–3288
  • Rizos EC, Ntzani EE, Bika E, Kostapanos MS, Elisaf MS. 2012. Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: a systematic review and meta-analysis. JAMA 308:1024–1033
  • Rondeau I, Picard S, Bah TM, Roy L, Godbout R, Rousseau G. 2011. Effects of different dietary omega-6/3 polyunsaturated fatty acids ratios on infarct size and the limbic system after myocardial infarction. Can J Physiol Pharmacol 89:169–176
  • Ross BM. 2007. Omega-3 fatty acid deficiency in major depressive disorder is caused by the interaction between diet and a genetically determined abnormality in phospholipid metabolism. Med Hypotheses 68:515–524
  • Sakai M, Kakutani S, Horikawa C, Tokuda H, Kawashima H, Shibata H, Okubo H, Sasaki S. 2012. Arachidonic acid and cancer risk: a systematic review of observational studies. BMC Cancer 12:606
  • Sanchez-Villegas A, Martinez-Gonzalez MA. 2013. Diet, a new target to prevent depression? BMC Med 11:3
  • Sanchez-Villegas A, Martinez-Gonzalez MA, Estruch R, Salas-Salvado J, Corella D, Covas MI, Aros F, et al. 2013. Mediterranean dietary pattern and depression: the PREDIMED randomized trial. BMC Med 11:208
  • Sanders TA, Lewis F, Slaughter S, Griffin BA, Griffin M, Davies I, Millward DJ, et al. 2006. Effect of varying the ratio of n-6 to n-3 fatty acids by increasing the dietary intake of alpha-linolenic acid, eicosapentaenoic and docosahexaenoic acid, or both on fibrinogen and clotting factors VII and XII in persons aged 45–70 y: the OPTILIP study. Am J Clin Nutr 84:513–522
  • Schwartz B. 2014. New criteria for supplementation of selected micronutrients in the era of nutrigenetics and nutrigenomics. Int J Food Sci Nutr 65:529–538
  • Scorletti E, Byrne CD. 2013. Omega-3 fatty acids, hepatic lipid metabolism, and nonalcoholic fatty liver disease. Annu Rev Nutr 33:231–248
  • Serhan CN. 2010. Novel lipid mediators and resolution mechanisms in acute inflammation: to resolve or not? Am J Pathol 177:1576–1591
  • Serini S, Fasano E, Piccioni E, Cittadini AR, Calviello G. 2011. Differential anti-cancer effects of purified EPA and DHA and possible mechanisms involved. Curr Med Chem 18:4065–4075
  • Serini S, Piccioni E, Merendino N, Calviello G. 2009. Dietary polyunsaturated fatty acids as inducers of apoptosis: implications for cancer. Apoptosis 14:135–152
  • Shen XJ, Zhou JD, Dong JY, Ding WQ, Wu JC. 2012. Dietary intake of n-3 fatty acids and colorectal cancer risk: a meta-analysis of data from 489 000 individuals. Br J Nutr 108:1550–1556
  • Shoji T, Kakiya R, Hayashi T, Tsujimoto Y, Sonoda M, Shima H, Mori K, et al. 2013. Serum n-3 and n-6 polyunsaturated fatty acid profile as an independent predictor of cardiovascular events in hemodialysis patients. Am J Kidney Dis 62:568–576
  • Simopoulos AP. 2006. Evolutionary aspects of diet, the omega-6/omega-3 ratio and genetic variation: nutritional implications for chronic diseases. Biomed Pharmacother 60:502–507
  • Simopoulos AP. 2008. The importance of the omega-6/omega-3 fatty acid ratio in cardiovascular disease and other chronic diseases. Exp Biol Med (Maywood) 233:674–688
  • Simopoulos AP. 2009. Evolutionary aspects of the dietary omega-6:omega-3 fatty acid ratio: medical implications. World Rev Nutr Diet 100:1–21
  • Skender B, Vaculova AH, Hofmanova J. 2012. Docosahexaenoic fatty acid (DHA) in the regulation of colon cell growth and cell death: a review. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 156:186–199
  • Sofi F, Macchi C, Abbate R, Gensini GF, Casini A. 2014. Mediterranean diet and health status: an updated meta-analysis and a proposal for a literature-based adherence score. Public Health Nutr 17:2769–2782
  • Song Z, Yang L, Shu G, Lu H, Sun G. 2013. Effects of the n-6/n-3 polyunsaturated fatty acids ratio on postprandial metabolism in hypertriacylglycerolemia patients. Lipids Health Dis 12:181
  • Spencer L, Mann C, Metcalfe M, Webb M, Pollard C, Spencer D, Berry D, et al. 2009. The effect of omega-3 FAs on tumour angiogenesis and their therapeutic potential. Eur J Cancer 45:2077–2086
  • Sublette ME, Galfalvy HC, Hibbeln JR, Keilp JG, Malone KM, Oquendo MA, Mann JJ. 2014. Polyunsaturated fatty acid associations with dopaminergic indices in major depressive disorder. Int J Neuropsychopharmacol 17:383–391
  • Taha AY, Cheon Y, Faurot KF, Macintosh B, Majchrzak-Hong SF, Mann JD, Hibbeln JR, et al. 2014. Dietary omega-6 fatty acid lowering increases bioavailability of omega-3 polyunsaturated fatty acids in human plasma lipid pools. Prostaglandins Leukot Essent Fatty Acids 90:151–157
  • Thiebaut AC, Chajes V, Gerber M, Boutron-Ruault MC, Joulin V, Lenoir G, Berrino F, et al. 2009. Dietary intakes of omega-6 and omega-3 polyunsaturated fatty acids and the risk of breast cancer. Int J Cancer 124:924–931
  • Tsai AC, Lucas M, Okereke OI, O'reilly EJ, Mirzaei F, Kawachi I, Ascherio A, Willett WC. 2014. Suicide mortality in relation to dietary intake of n-3 and n-6 polyunsaturated fatty acids and fish: equivocal findings from 3 large US cohort studies. Am J Epidemiol 179:1458–1466
  • Vafeiadou K, Weech M, Sharma V, Yaqoob P, Todd S, Williams CM, Jackson KG, Lovegrove JA. 2012. A review of the evidence for the effects of total dietary fat, saturated, monounsaturated and n-6 polyunsaturated fatty acids on vascular function, endothelial progenitor cells and microparticles. Br J Nutr 107:303–324
  • Valenzuela R, Videla LA. 2011. The importance of the long-chain polyunsaturated fatty acid n-6/n-3 ratio in development of non-alcoholic fatty liver associated with obesity. Food Funct 2:644–648
  • Vaz JS, Kac G, Nardi AE, Hibbeln JR. 2014. Omega-6 fatty acids and greater likelihood of suicide risk and major depression in early pregnancy. J Affect Disord 152–154:76–82
  • Venna VR, Deplanque D, Allet C, Belarbi K, Hamdane M, Bordet R. 2009. PUFA induce antidepressant-like effects in parallel to structural and molecular changes in the hippocampus. Psychoneuroendocrinology 34:199–211
  • Wall R, Ross RP, Fitzgerald GF, Stanton C. 2010. Fatty acids from fish: the anti-inflammatory potential of long-chain omega-3 fatty acids. Nutr Rev 68:280–289
  • Wan JB, Huang LL, Rong R, Tan R, Wang J, Kang JX. 2010. Endogenously decreasing tissue n-6/n-3 fatty acid ratio reduces atherosclerotic lesions in apolipoprotein E-deficient mice by inhibiting systemic and vascular inflammation. Arterioscler Thromb Vasc Biol 30:2487–2494
  • Wang Q, Liang X, Wang L, Lu X, Huang J, Cao J, Li H, Gu D. 2012. Effect of omega-3 fatty acids supplementation on endothelial function: a meta-analysis of randomized controlled trials. Atherosclerosis 221:536–543
  • Wen YT, Dai JH, Gao Q. 2014. Effects of Omega-3 fatty acid on major cardiovascular events and mortality in patients with coronary heart disease: a meta-analysis of randomized controlled trials. Nutr Metab Cardiovasc Dis 24:470–475
  • Wolfe AR, Ogbonna EM, Lim S, Li Y, Zhang J. 2009. Dietary linoleic and oleic fatty acids in relation to severe depressed mood: 10 years follow-up of a national cohort. Prog Neuropsychopharmacol Biol Psychiatry 33:972–977
  • Yamashita T, Oda E, Sano T, Yamashita T, Ijiru Y, Giddings JC, Yamamoto J. 2005. Varying the ratio of dietary n-6/n-3 polyunsaturated fatty acid alters the tendency to thrombosis and progress of atherosclerosis in apoE-/- LDLR-/- double knockout mouse. Thromb Res 116:393–401
  • Yang Y, Lu N, Chen D, Meng L, Zheng Y, Hui R. 2012. Effects of n-3 PUFA supplementation on plasma soluble adhesion molecules: a meta-analysis of randomized controlled trials. Am J Clin Nutr 95:972–980
  • Zhao YT, Chen Q, Sun YX, Li XB, Zhang P, Xu Y, Guo JH. 2009. Prevention of sudden cardiac death with omega-3 fatty acids in patients with coronary heart disease: a meta-analysis of randomized controlled trials. Ann Med 41:301–310
  • Zheng JS, Hu XJ, Zhao YM, Yang J, Li D. 2013. Intake of fish and marine n-3 polyunsaturated fatty acids and risk of breast cancer: meta-analysis of data from 21 independent prospective cohort studies. BMJ 346:f3706
  • Zock PL, Katan MB. 1998. Linoleic acid intake and cancer risk: a review and meta-analysis. Am J Clin Nutr 68:142–153

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.