In the last decades, the development of new technologies applied to lipidomics has revitalized the analysis of lipid profile alterations and the understanding of the underlying molecular mechanisms of lipid metabolism, together with their involvement in the occurrence of human disease. Of particular interest is the study of omega-3 and omega-6 long chain polyunsaturated fatty acids (LC-PUFAs), notably EPA (eicosapentaenoic acid, 20:5n-3), DHA (docosahexaenoic acid, 22:6n-3), and ARA (arachidonic acid, 20:4n-6), and their transformation into bioactive lipid mediators. In this sense, new families of PUFA-derived lipid mediators, including resolvins derived from EPA and DHA, and protectins and maresins derived from DHA, are being increasingly investigated because of their active role in the "return to homeostasis" process and resolution of inflammation. Recent findings reviewed in the present study highlight that the omega-6 fatty acid ARA appears increased, and omega-3 EPA and DHA decreased in most cancer tissues compared to normal ones, and that increments in omega-3 LC-PUFAs consumption and an omega-6/omega-3 ratio of 2-4:1, are associated with a reduced risk of breast, prostate, colon and renal cancers. Along with their lipid-lowering properties, omega-3 LC-PUFAs also exert cardioprotective functions, such as reducing platelet aggregation and inflammation, and controlling the presence of DHA in our body, especially in our liver and brain, which is crucial for optimal brain functionality. Considering that DHA is the principal omega-3 FA in cortical gray matter, the importance of DHA intake and its derived lipid mediators have been recently reported in patients with major depressive and bipolar disorders, Alzheimer disease, Parkinson's disease, and amyotrophic lateral sclerosis. The present study reviews the relationships between major diseases occurring today in the Western world and LC-PUFAs. More specifically this review focuses on the dietary omega-3 LC-PUFAs and the omega-6/omega-3 balance, in a wide range of inflammation disorders, including autoimmune diseases. This review suggests that the current recommendations of consumption and/or supplementation of omega-3 FAs are specific to particular groups of age and physiological status, and still need more fine tuning for overall human health and well being.

Canary Islands Cancer Research Institute Ave La Trinidad 61 Torre A Arévalo 7th floor 38204 La Laguna Tenerife Spain

Centre Algatech Institute of Microbiology Academy of Sciences of the Czech Republic Třeboň Czech Republic

Department of Animal Biology Soil Science and Geology Faculty of Sciences Universidad de La Laguna Ave Astrofísico Francisco Sánchez s n 38206 La Laguna Tenerife Spain

Department of Nutrition and Preventive Medicine Norwich Medical School University of East Anglia Norwich NR4 7UQ UK

Institute of Biomedical Technologies Universidad de La Laguna Campus de Ofra 38071 La Laguna Tenerife Spain

See more in PubMed

Bogyo M, Rudd PM. New technologies and their impact on ‘omics’ research. Curr Opin Chem Biol. 2013;17(1):1–3. doi: 10.1016/j.cbpa.2013.01.005. PubMed DOI

Simo C, Cifuentes A, GarciaCanas V. Fundamentals of advanced omics technologies: from genes to metabolites. Amsterdam: Elsevier Science Bv; 2014.

Debnath M, Prasad GBKS, Bisen PS. Omics technology. molecular diagnostics: promises and possibilities. Dordrecht: Springer Netherlands; 2010. pp. 11–31.

Dennis EA. Lipidomics joins the omics evolution. Proc Natl Acad Sci USA. 2009;106(7):2089–2090. doi: 10.1073/pnas.0812636106. PubMed DOI PMC

Brown HA. Lipidomics: when apocrypha becomes canonical. Curr Opin Chem Biol. 2012;16(1–2):221–226. doi: 10.1016/j.cbpa.2012.02.003. PubMed DOI PMC

Hu CX, van der Heijden R, Wang M, van der Greef J, Hankemeier T, Xua GW. Analytical strategies in lipidomics and applications in disease biomarker discovery. J Chromatogr B. 2009;877(26):2836–2846. doi: 10.1016/j.jchromb.2009.01.038. PubMed DOI

Köfeler HC, Fauland A, Rechberger GN, Trötzmüller M. Mass spectrometry based lipidomics: an overview of technological platforms. Metabolites. 2012;2(1):19–38. doi: 10.3390/metabo2010019. PubMed DOI PMC

Dewick PM (2001) The acetate pathway: fatty acids and polyketides. In: Medicinal natural products: A biosynthetic approach, 2nd edn. Wiley, Chichester, p 35–120

Christie WW, Han X. Lipid analysis isolation, separation, identification and lipidomic analysis. 4. Bridgewater: Oily Press; 2010.

Calder PC. Functional roles of fatty acids and their effects on human health. J Parenter Enteral Nutr. 2015;39(Suppl 1):18–32. doi: 10.1177/0148607115595980. PubMed DOI

Sayanova OV, Napier JA. Eicosapentaenoic acid: biosynthetic routes and the potential for synthesis in transgenic plants. Phytochemistry. 2004;65(2):147–158. doi: 10.1016/j.phytochem.2003.10.017. PubMed DOI

Sprecher H, Chen Q, Yin FQ. Regulation of the biosynthesis of 22: 5n-6 and 22: 6n-3: a complex intracellular process. Lipids. 1999;34(1):153–156. doi: 10.1007/BF02562271. PubMed DOI

Buzzi M, Henderson RJ, Sargent JR. Biosynthesis of docosahexaenoic acid in trout hepatocytes proceeds via 24-carbon intermediates. Comp Biochem Physiol B Biochem Mol Biol. 1997;116(2):263–267. doi: 10.1016/S0305-0491(96)00210-6. PubMed DOI

Rodríguez C, Pérez JA, Henderson RJ. The esterification and modification of n-3 and n-6 polyunsaturated fatty acids by hepatocytes and liver microsomes of turbot (Scophthalmus maximus) Comp Biochem Physiol B Biochem Mol Biol. 2002;132(3):559–570. doi: 10.1016/S1096-4959(02)00072-6. PubMed DOI

Venegas-Calerón M, Beaudoin F, Sayanova O, Napier JA. Co-transcribed Genes for Long Chain Polyunsaturated Fatty Acid Biosynthesis in the Protozoon Perkinsus marinus include a plant-like FAE1 3-ketoacyl coenzyme a synthase. J Biol Chem. 2007;282(5):2996–3003. doi: 10.1074/jbc.M607051200. PubMed DOI

Kothapalli KS, Ye K, Gadgil MS, Carlson SE, O’Brien KO, Zhang JY, et al. Positive selection on a regulatory insertion-deletion polymorphism in FADS2 influences apparent endogenous synthesis of arachidonic acid. Mol Biol Evol. 2016;29:msw049. PubMed PMC

Burdge GC, Jones AE, Wootton SA. Eicosapentaenoic and docosapentaenoic acids are the principal products of α-linolenic acid metabolism in young men. Br J Nutr. 2002;88(04):355–363. doi: 10.1079/BJN2002662. PubMed DOI

Hussein N, Ah-Sing E, Wilkinson P, Leach C, Griffin BA, Millward DJ. Long-chain conversion of [13C]linoleic acid and α-linolenic acid in response to marked changes in their dietary intake in men. J Lipid Res. 2005;46(2):269–280. doi: 10.1194/jlr.M400225-JLR200. PubMed DOI

Bradbury J. Docosahexaenoic acid (DHA): an ancient nutrient for the modern human brain. Nutrients. 2011;3(5):529–554. doi: 10.3390/nu3050529. PubMed DOI PMC

Plourde M, Cunnane SC. Extremely limited synthesis of long chain polyunsaturates in adults: implications for their dietary essentiality and use as supplements. Appl Physiol Nutr Metab. 2007;32(4):619–634. doi: 10.1139/H07-034. PubMed DOI

Jacobson DL, Gange SJ, Rose NR, Graham NMH. Epidemiology and estimated population burden of selected autoimmune diseases in the United States. Clin Immunol Immunopathol. 1997;84(3):223–243. doi: 10.1006/clin.1997.4412. PubMed DOI

Davidson A, Diamond B. Autoimmune diseases. New Engl J Medicine Adv Inmunol. 2001;345:340–350. doi: 10.1056/NEJM200108023450506. PubMed DOI

Nakazawa DJ. The autoimmune epidemic: bodies gone haywire in a world out of balance. New York: Touchstone/Simon & Schuster; 2009.

Simopoulos AP. Evolutionary aspects of diet and essential fatty acids. Fatty Acids Lipids New Find: Karger Publishers; 2001. PubMed

Simopoulos AP. An increase in the omega-6/omega-3 fatty acid ratio increases the risk for obesity. Nutrients. 2016;8(3):1–17. doi: 10.3390/nu8030128. PubMed DOI PMC

Borges MC, Santos FDM, Telles RW, Correia M, Lanna CCD. Polyunsaturated omega-3 fatty acids and systemic lupus erythematosus: what do we know? Rev Bras Reumatol. 2014;54(6):459–466. doi: 10.1016/j.rbr.2013.12.002. PubMed DOI

Calder PC. Fatty acids and inflammation: the cutting edge between food and pharma. Eur J Pharmacol. 2011;668(Suppl):50–58. doi: 10.1016/j.ejphar.2011.05.085. PubMed DOI

Calder PC. Omega-3 polyunsaturated fatty acids and inflammatory processes: nutrition or pharmacology? Br J Clin Pharmacol. 2013;75(3):645–662. doi: 10.1111/j.1365-2125.2012.04374.x. PubMed DOI PMC

Calder PC. Mechanisms of Action of (n-3) Fatty Acids. J Nutr. 2012;142(3):592S–599S. doi: 10.3945/jn.111.155259. PubMed DOI

Buczynski MW, Dumlao DS, Dennis EA. An integrated omics analysis of eicosanoid biology. J Lipid Res. 2009;50(6):1015–1038. doi: 10.1194/jlr.R900004-JLR200. PubMed DOI PMC

Smith WL, DeWitt DL, Garavito RM. Cyclooxygenases: structural, cellular, and molecular biology. Annu Rev Biochem. 2000;69:145–182. doi: 10.1146/annurev.biochem.69.1.145. PubMed DOI

Kuhn H, O’Donnell VB. Inflammation and immune regulation by 12/15-lipoxygenases. Prog Lipid Res. 2006;45(4):334–356. doi: 10.1016/j.plipres.2006.02.003. PubMed DOI

Morisseau C, Hammock BD. Impact of soluble epoxide hydrolase and epoxyeicosanoids on human health. Annu Rev Pharmacol Toxicol. 2013;53:37–58. doi: 10.1146/annurev-pharmtox-011112-140244. PubMed DOI PMC

Serhan CN, Chiang N, Dalli J, Levy BD. Lipid mediators in the resolution of inflammation. Cold Spring Harbor Perspect Biol. 2015;7(2):a016311. doi: 10.1101/cshperspect.a016311. PubMed DOI PMC

Gross O, Thomas CJ, Guarda G, Tschopp J. The inflammasome: an integrated view. Immunol Rev. 2011;243:136–151. doi: 10.1111/j.1600-065X.2011.01046.x. PubMed DOI

Latz E, Xiao TS, Stutz A. Activation and regulation of the inflammasomes. Nat Rev Immunol. 2013;13(6):397–411. doi: 10.1038/nri3452. PubMed DOI PMC

Dennis EA, Norris PC. Eicosanoid storm in infection and inflammation. Nat Rev Immunol. 2015;15(8):511–523. doi: 10.1038/nri3859. PubMed DOI PMC

Pieters DJM, Mensink RP. Effects of stearidonic acid on serum triacylglycerol concentrations in overweight and obese subjects: a randomized controlled trial. Eur J Clin Nutr. 2015;69(1):121–126. doi: 10.1038/ejcn.2014.193. PubMed DOI

Klemens CM, Berman DR, Mozurkewich EL. The effect of perinatal omega-3 fatty acid supplementation on inflammatory markers and allergic diseases: a systematic review. BJOG. 2011;118(8):916–925. doi: 10.1111/j.1471-0528.2010.02846.x. PubMed DOI

Norris PC, Dennis EA. Omega-3 fatty acids cause dramatic changes in TLR4 and purinergic eicosanoid signaling. Proc Natl Acad Sci USA. 2012;109(22):8517–8522. doi: 10.1073/pnas.1200189109. PubMed DOI PMC

Maskrey BH, Megson IL, Rossi AG, Whitfield PD. Emerging importance of omega-3 fatty acids in the innate immune response: molecular mechanisms and lipidomic strategies for their analysis. Mol Nutr Food Res. 2013;57(8):1390–1400. doi: 10.1002/mnfr.201200723. PubMed DOI

Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, et al. Heart disease and stroke statistics-2017 update a report from the American Heart Association. Circulation. 2017;135(10):E146–E603. doi: 10.1161/CIR.0000000000000485. PubMed DOI PMC

Cannon CP. Cardiovascular disease and modifiable cardiometabolic risk factors. Clin Cornerstone. 2007;8(3):11–28. doi: 10.1016/S1098-3597(07)80025-1. PubMed DOI

Mozaffarian D, Appel LJ, Van Horn L. Components of a cardioprotective diet new insights. Circulation. 2011;123(24):2870–2891. doi: 10.1161/CIRCULATIONAHA.110.968735. PubMed DOI PMC

Saravanan P, Davidson NC, Schmidt EB, Calder PC. Cardiovascular effects of marine omega-3 fatty acids. Lancet. 2010;376(9740):540–550. doi: 10.1016/S0140-6736(10)60445-X. PubMed DOI

Cunnane S, Drevon C, Harris W, Sinclair A, Spector A. Recommendations for intakes of polyunsaturated fatty acids in healthy adults. ISSFAL Newsl. 2004;11(2):12–25.

Scientific Advisory Committee on Nutrition (2004) Advice on fish consumption: benefits and risks. Stationery office. TSO, Norwich. ISBN 0 11 243083 X. https://cot.food.gov.uk/sites/default/files/cot/fishreport200401.pdf

Kris-Etherton PM, Harris WS, Appel LJ, Nutrition C. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation. 2002;106(21):2747–2757. doi: 10.1161/01.CIR.0000038493.65177.94. PubMed DOI

Harris WS, Miller M, Tighe AP, Davidson MH, Schaefer EJ. Omega-3 fatty acids and coronary heart disease risk: clinical and mechanistic perspectives. Atherosclerosis. 2008;197(1):12–24. doi: 10.1016/j.atherosclerosis.2007.11.008. PubMed DOI

Mozaffarian D, Wu JHY. Omega-3 fatty acids and cardiovascular disease effects on risk factors, molecular pathways, and clinical events. J Am Coll Cardiol. 2011;58(20):2047–2067. doi: 10.1016/j.jacc.2011.06.063. PubMed DOI

Huang CW, Chien YS, Chen YJ, Ajuwon KM, Mersmann HM, Ding ST. Role of n-3 polyunsaturated fatty acids in ameliorating the obesity-induced metabolic syndrome in animal models and humans. Int J Mol Sci. 2016;17(10):29. PubMed PMC

Lalia AZ, Lanza IR. Insulin-sensitizing effects of omega-3 fatty acids: lost in translation? Nutrients. 2016;8(6):24. doi: 10.3390/nu8060329. PubMed DOI PMC

Ricciotti E, FitzGerald GA. Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol. 2011;31(5):986–1000. doi: 10.1161/ATVBAHA.110.207449. PubMed DOI PMC

Imig JD. Epoxides and soluble epoxide hydrolase in cardiovascular physiology. Physiol Rev. 2012;92(1):101–130. doi: 10.1152/physrev.00021.2011. PubMed DOI PMC

Harris TR, Hammock BD. Soluble epoxide hydrolase: gene structure, expression and deletion. Gene. 2013;526(2):61–74. doi: 10.1016/j.gene.2013.05.008. PubMed DOI PMC

Serhan CN, Petasis NA. Resolvins and protectins in inflammation resolution. Chem Rev. 2011;111(10):5922–5943. doi: 10.1021/cr100396c. PubMed DOI PMC

Ulu A, Harris TR, Morisseau C, Miyabe C, Inoue H, Schuster G, et al. Anti-inflammatory effects of omega-3 polyunsaturated fatty acids and soluble epoxide hydrolase inhibitors in angiotensin-II-dependent hypertension. J Cardiovasc Pharmacol. 2013;62(3):285–297. doi: 10.1097/FJC.0b013e318298e460. PubMed DOI PMC

Morin C, Fortin S, Rousseau E. 19,20-EpDPE, a bioactive CYP450 metabolite of DHA monoacyglyceride, decreases Ca²⁺ sensitivity in human pulmonary arteries. Am J Physiol Heart Circ Physiol. 2011;301(4):H1311–H1318. doi: 10.1152/ajpheart.00380.2011. PubMed DOI

De Lorgeril M, Salen P, Defaye P, Rabaeus M. Recent findings on the health effects of omega-3 fatty acids and statins, and their interactions: do statins inhibit omega-3? BMC medicine. 2013;11(1):5. doi: 10.1186/1741-7015-11-5. PubMed DOI PMC

Hooper L, Thompson RL, Harrison RA, Summerbell CD, Ness AR, Moore HJ, et al. Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review. BMJ. 2006;332(7544):752–760. doi: 10.1136/bmj.38755.366331.2F. PubMed DOI PMC

Rizos EC, Ntzani EE, Bika E, Kostapanos MS, Elisaf MS. Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: a systematic review and meta-analysis. JAMA. 2012;308(10):1024–1033. doi: 10.1001/2012.jama.11374. PubMed DOI

Bang HO, Dyerberg J. Lipid metabolism and ischemic heart disease in Greenland Eskimos. In: Draper HH, editor. Advances in nutritional research. Boston: Springer; 1980. pp. 1–22.

Burr ML, Gilbert JF, Holliday RM, Elwood PC, Fehily AM, Rogers S, et al. Effects of changes in fat, fish and fiber intakes on death and myocardial reinfarction—diet and reinfarction trial (DART) Lancet. 1989;2(8666):757–761. doi: 10.1016/S0140-6736(89)90828-3. PubMed DOI

Investigators GI-P. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Lancet. 1999;354(9177):447–455. doi: 10.1016/S0140-6736(99)07072-5. PubMed DOI

Tavazzi L, Maggioni AP, Marchioli R, Barlera S, Franzosi MG, Latini R, et al. Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372(9645):1223–1230. doi: 10.1016/S0140-6736(08)61239-8. PubMed DOI

Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised openlabel, blinded endpoint analysis. Lancet. 2007;369(9567):1090–1098. doi: 10.1016/S0140-6736(07)60527-3. PubMed DOI

Kromhout D, Giltay EJ, Geleijnse JM. n-3 fatty acids and cardiovascular events after myocardial infarction. N Engl J Med. 2010;363(21):2015–2026. doi: 10.1056/NEJMoa1003603. PubMed DOI

Kromhout D, Geleijnse JM, de Goede J, Griep LMO, Mulder BJM, de Boer MJ, et al. n-3 fatty acids, ventricular arrhythmia-related events, and fatal myocardial infarction in postmyocardial infarction patients with diabetes. Diabetes Care. 2011;34(12):2515–2520. doi: 10.2337/dc11-0896. PubMed DOI PMC

Bowen KJ, Harris WS, Kris-Etherton PM. Omega-3 fatty acids and cardiovascular disease: are there benefits? Curr Treat Options Cardiovasc Med. 2016;18(11):69. doi: 10.1007/s11936-016-0487-1. PubMed DOI PMC

Harris WS, von Schacky C. The omega-3 index: a new risk factor for death from coronary heart disease? Prev Med. 2004;39(1):212–220. doi: 10.1016/j.ypmed.2004.02.030. PubMed DOI

Warburg O. On the origin of cancer cells. Science. 1956;123(3191):309–314. doi: 10.1126/science.123.3191.309. PubMed DOI

Tasevska N, Jiao L, Cross AJ, Kipnis V, Subar AF, Hollenbeck A, et al. Sugars in diet and risk of cancer in the NIH-AARP diet and health study. Int J Cancer. 2012;130(1):159–169. doi: 10.1002/ijc.25990. PubMed DOI PMC

Yao CH, Fowle-Grider R, Mahieu NG, Liu GY, Chen Y, Wang RC, et al. Exogenous fatty acids are the preferred source of membrane lipids in proliferating fibroblasts. Cell Chem Biol. 2016;23(4):483–493. doi: 10.1016/j.chembiol.2016.03.007. PubMed DOI PMC

Bergers G, Benjamin LE. Tumorigenesis and the angiogenic switch. Nat Rev Cancer. 2003;3(6):401–410. doi: 10.1038/nrc1093. PubMed DOI

Gupta GP, Massague J. Cancer metastasis: building a framework. Cell. 2006;127(4):679–695. doi: 10.1016/j.cell.2006.11.001. PubMed DOI

Currie E, Schulze A, Zechner R, Walther TC, Farese RV. Cellular fatty acid metabolism and cancer. Cell Metab. 2013;18(2):153–161. doi: 10.1016/j.cmet.2013.05.017. PubMed DOI PMC

Zhang F, Du G. Dysregulated lipid metabolism in cancer. World J Biol Chem. 2012;3(8):167–174. doi: 10.4331/wjbc.v3.i8.167. PubMed DOI PMC

Kelloff G, Hoffman JM, Johnson B, Scher HI, Siegel BA, Cheng EY, et al. Progress and promise of FDG-PET imaging for cancer patient management and oncologic drug development. Clin Cancer Res. 2005;11(8):2785–2808. doi: 10.1158/1078-0432.CCR-04-2626. PubMed DOI

Santos CR, Schulze A. Lipid metabolism in cancer. FEBS J. 2012;279(15):2610–2623. doi: 10.1111/j.1742-4658.2012.08644.x. PubMed DOI

Beloribi-Djefaflia S, Vasseur S, Guillaumond F. Lipid metabolic reprogramming in cancer cells. Oncogenesis. 2016;5(1):e189. doi: 10.1038/oncsis.2015.49. PubMed DOI PMC

Menendez JA, Lupu R. Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nat Rev Cancer. 2007;7(10):763–777. doi: 10.1038/nrc2222. PubMed DOI

Zaidi N, Swinnen JV, Smans K. ATP-citrate lyase: a key player in cancer metabolism. Cancer Res. 2012;72(15):3709–3714. doi: 10.1158/0008-5472.CAN-11-4112. PubMed DOI

Baenke F, Peck B, Miess H, Schulze A. Hooked on fat: the role of lipid synthesis in cancer metabolism and tumour development. Dis Model Mech. 2013;6(6):1353–1363. doi: 10.1242/dmm.011338. PubMed DOI PMC

Miryaghoubzadeh J, Darabi M, Madaen K, Shaaker M, Mehdizadeh A, Hajihosseini R. Tissue fatty acid composition in human urothelial carcinoma. Br J Biomed Sci. 2013;70(1):1–5. doi: 10.1080/09674845.2013.11669921. PubMed DOI

Jurczyszyn A, Czepiel J, Gdula-Argasinska J, Pasko P, Czapkiewicz A, Librowski T, et al. Plasma fatty acid profile in multiple myeloma patients. Leuk Res. 2015;39(4):400–405. doi: 10.1016/j.leukres.2014.12.010. PubMed DOI

Mohammadzadeh F, Mosayebi G, Montazeri V, Darabi M, Fayezi S, Shaaker M, et al. Fatty acid composition of tissue cultured breast carcinoma and the effect of stearoyl-CoA desaturase 1 inhibition. J Breast Cancer. 2014;17(2):136–142. doi: 10.4048/jbc.2014.17.2.136. PubMed DOI PMC

Omabe M, Ezeani M, Omabe KN. Lipid metabolism and cancer progression: the missing target in metastatic cancer treatment. J Appl Biomed. 2015;13(1):47–59. doi: 10.1016/j.jab.2014.09.004. DOI

Balaban S, Lee LS, Schreuder M, Hoy AJ. Obesity and cancer progression: is there a role of fatty acid metabolism? Biomed Res Int. 2015;2015:1–17. doi: 10.1155/2015/274585. PubMed DOI PMC

Zamaria N. Alteration of polyunsaturated fatty acid status and metabolism in health and disease. Reprod Nutr Dev. 2004;44(3):273–282. doi: 10.1051/rnd:2004034. PubMed DOI

Gleissman H, Johnsen JI, Kogner P. Omega-3 fatty acids in cancer, the protectors of good and the killers of evil? Exp Cell Res. 2010;316(8):1365–1373. doi: 10.1016/j.yexcr.2010.02.039. PubMed DOI

Simopoulos AP. The importance of the omega-6/omega-3 fatty acid ratio in cardiovascular disease and other chronic diseases. Exp Biol Med. 2008;233(6):674–688. doi: 10.3181/0711-MR-311. PubMed DOI

Huang CF, Freter C. Lipid metabolism, apoptosis and cancer therapy. Int J Mol Sci. 2015;16(1):924–949. doi: 10.3390/ijms16010924. PubMed DOI PMC

Cai W, Zhang K, Li PY, Zhu L, Xu J, Yang BY, et al. Dysfunction of the neurovascular unit in ischemic stroke and neurodegenerative diseases: an aging effect. Ageing Res Rev. 2017;34:77–87. doi: 10.1016/j.arr.2016.09.006. PubMed DOI PMC

Bertram L, Tanzi RE. The genetic epidemiology of neurodegenerative disease. J Clin Investig. 2005;115(6):1449–1457. doi: 10.1172/JCI24761. PubMed DOI PMC

Tsuji S. Genetics of neurodegenerative diseases: insights from high-throughput resequencing. Hum Mol Genet. 2010;19(R1):R65–R70. doi: 10.1093/hmg/ddq162. PubMed DOI PMC

Cunnane SC, Plourde M, Pifferi F, Begin M, Feart C, Barberger-Gateau P. Fish, docosahexaenoic acid and Alzheimer’s disease. Prog Lipid Res. 2009;48(5):239–256. doi: 10.1016/j.plipres.2009.04.001. PubMed DOI

McNamara RK. DHA deficiency and prefrontal cortex neuropathology in recurrent affective disorders. J Nutr. 2010;140(4):864–868. doi: 10.3945/jn.109.113233. PubMed DOI PMC

Torres M, Price SL, Fiol-deRoque MA, Marcilla-Etxenike A, Ahyayauch H, Barcelo-Coblijn G, et al. Membrane lipid modifications and therapeutic effects mediated by hydroxydocosahexaenoic acid on Alzheimer’s disease. Biochim Biophys Acta Biomembr. 2014;1838(6):1680–1692. doi: 10.1016/j.bbamem.2013.12.016. PubMed DOI

Blennow K, de Leon MJ, Zetterberg H. Alzheimer’s disease. Lancet. 2006;368(9533):387–403. doi: 10.1016/S0140-6736(06)69113-7. PubMed DOI

Bazan NG. Cellular and molecular events mediated by docosahexaenoic acid-derived neuroprotectin D1 signaling in photoreceptor cell survival and brain protection. Prostaglandins Leukot Essent Fatty Acids. 2009;81(2–3):205–211. doi: 10.1016/j.plefa.2009.05.024. PubMed DOI PMC

McNamara RK, Jandacek R, Rider T, Tso P, Dwivedi Y, Pandey GN. Selective deficits in erythrocyte docosahexaenoic acid composition in adult patients with bipolar disorder and major depressive disorder. J Affect Disord. 2010;126(1–2):303–311. doi: 10.1016/j.jad.2010.03.015. PubMed DOI PMC

Astarita G, Jung KM, Berchtold NC, Nguyen VQ, Gillen DL, Head E, et al. Deficient liver biosynthesis of docosahexaenoic acid correlates with cognitive impairment in Alzheimer’s Disease. PLoS ONE. 2010;5(9):1–8. doi: 10.1371/journal.pone.0012538. PubMed DOI PMC

Nasaruddin ML, Hölscher C, Kehoe P, Graham SF, Green BD. Wide-ranging alterations in the brain fatty acid complement of subjects with late Alzheimer’s disease as detected by GC–MS. Am J Transl Res. 2016;8(1):154–165. PubMed PMC

Cunnane SC, Schneider JA, Tangney C, Tremblay-Mercier J, Fortier M, Bennett DA, et al. Plasma and brain fatty acid profiles in mild cognitive impairment and Alzheimer’s disease. J Alzheimers Dis. 2012;29(3):691–697. PubMed PMC

Shahar DR, Schwarzfuchs D, Fraser D, Vardi H, Thiery J, Fiedler GM, et al. Dairy calcium intake, serum vitamin D, and successful weight loss. Am J Clin Nutr. 2010;92(5):1017–1022. doi: 10.3945/ajcn.2010.29355. PubMed DOI

Dyall SC. Long-chain omega-3 fatty acids and the brain: a review of the independent and shared effects of EPA, DPA and DHA. Front Aging Neurosci. 2015;7:52. doi: 10.3389/fnagi.2015.00052. PubMed DOI PMC

Samieri C, Maillard P, Crivello F, Proust-Lima C, Peuchant E, Helmer C, et al. Plasma long-chain omega-3 fatty acids and atrophy of the medial temporal lobe. Neurology. 2012;79(7):642–650. doi: 10.1212/WNL.0b013e318264e394. PubMed DOI

Heppner FL, Ransohoff RM, Becher B. Immune attack: the role of inflammation in Alzheimer disease. Nat Rev Neurosci. 2015;16(6):358–372. doi: 10.1038/nrn3880. PubMed DOI

Heras-Sandoval D, Pedraza-Chaverri J, Perez-Rojas JM. Role of docosahexaenoic acid in the modulation of glial cells in Alzheimer’s disease. J Neuroinflamm. 2016;13:61. doi: 10.1186/s12974-016-0525-7. PubMed DOI PMC

Hashimoto M, Shahdat HM, Yamashita S, Katakura M, Tanabe Y, Fujiwara H, et al. Docosahexaenoic acid disrupts in vitro amyloid beta(1-40) fibrillation and concomitantly inhibits amyloid levels in cerebral cortex of Alzheimer’s disease model rats. J Neurochem. 2008;107(6):1634–1646. doi: 10.1111/j.1471-4159.2008.05731.x. PubMed DOI

Grimm MOW, Mett J, Stahlmann CP, Haupenthal VJ, Blumel T, Stotzel H, et al. Eicosapentaenoic acid and docosahexaenoic acid increase the degradation of amyloid-beta by affecting insulin-degrading enzyme. Biochem Cell Biol. 2016;94(6):534–542. doi: 10.1139/bcb-2015-0149. PubMed DOI

Morgese MG, Tucci P, Mhillaj E, Bove M, Schiavone S, Trabace L, et al. Lifelong nutritional omega-3 deficiency evokes depressive-like state through soluble beta amyloid. Mol Neurobiol. 2017;54(3):2079–2089. doi: 10.1007/s12035-016-9809-2. PubMed DOI PMC

Colaianna M, Tucci P, Zotti M, Morgese MG, Schiavone S, Govoni S, et al. Soluble β amyloid1-42: a critical player in producing behavioural and biochemical changes evoking depressive-related state? Br J Pharmacol. 2010;159(8):1704–1715. doi: 10.1111/j.1476-5381.2010.00669.x. PubMed DOI PMC

Osorio RS, Gumb T, Pomara N. Soluble amyloid-beta levels and late-life depression. Curr Pharm Des. 2014;20(15):2547–2554. doi: 10.2174/13816128113199990502. PubMed DOI PMC

Pomara N, Bruno D. Major depression may lead to elevations in potentially neurotoxic amyloid beta species independently of Alzheimer Disease. Am J Geriatr Psychiatr. 2016;24(9):773–775. doi: 10.1016/j.jagp.2016.05.003. PubMed DOI

Hashimoto M, Katakura M, Hossain S, Rahman A, Shimada T, Shido O. Docosahexaenoic acid withstands the a beta(25-35)-induced neurotoxicity in SH-SY5Y cells. J Nutr Biochem. 2011;22(1):22–29. doi: 10.1016/j.jnutbio.2009.11.005. PubMed DOI

Ledo JH, Azevedo EP, Clarke JR, Ribeiro FC, Figueiredo CP, Foguel D, et al. Amyloid-beta oligomers link depressive-like behavior and cognitive deficits in mice. Mol Psychiatr. 2013;18(10):1053–1054. doi: 10.1038/mp.2012.168. PubMed DOI PMC

Ren HX, Luo CM, Feng YQ, Yao XL, Shi Z, Liang FY, et al. Omega-3 polyunsaturated fatty acids promote amyloid-beta clearance from the brain through mediating the function of the glymphatic system. Faseb J. 2017;31(1):282–293. doi: 10.1096/fj.201600896. PubMed DOI

Oster T, Pillot T. Docosahexaenoic acid and synaptic protection in Alzheimer’s disease mice. Biochim Biophys Acta Mol Cell Biol Lipids. 2010;1801(8):791–798. doi: 10.1016/j.bbalip.2010.02.011. PubMed DOI

Bazan NG. Neuroprotectin D1-mediated anti-inflammatory and survival signaling in stroke, retinal degenerations, and Alzheimer’s disease. J Lipid Res. 2009;50(Suppl):400–405. doi: 10.1194/jlr.R800068-JLR200. PubMed DOI PMC

Goetz CG. The history of Parkinson’s disease: early clinical descriptions and neurological therapies. Cold Spring Harb Perspect Med. 2011;1:1. doi: 10.1101/cshperspect.a008862. PubMed DOI PMC

Vinot N, Jouin M, Lhomme-Duchadeuil A, Guesnet P, Alessandri JM, Aujard F, et al. Omega-3 Fatty acids from fish oil lower anxiety, improve cognitive functions and reduce spontaneous locomotor activity in a non-human primate. PLoS ONE. 2011;6:6. doi: 10.1371/journal.pone.0020491. PubMed DOI PMC

Bousquet M, Saint-Pierre M, Julien C, Salem N, Cicchetti F, Calon F. Beneficial effects of dietary omega-3 polyunsaturated fatty acid on toxin-induced neuronal degeneration in an animal model of Parkinson’s disease. Faseb J. 2008;22(4):1213–1225. doi: 10.1096/fj.07-9677com. PubMed DOI

Ozkan A, Parlak H, Tanriover G, Dilmac S, Ulker SN, Birsen L, et al. The protective mechanism of docosahexaenoic acid in mouse model of Parkinson: the role of heme oxygenase. Neurochem Int. 2016;101:110–119. doi: 10.1016/j.neuint.2016.10.012. PubMed DOI

Bousquet M, Gue K, Emond V, Julien P, Kang JX, Cicchetti F, et al. Transgenic conversion of omega-6 into omega-3 fatty acids in a mouse model of Parkinson’s disease. J Lipid Res. 2011;52(2):263–271. doi: 10.1194/jlr.M011692. PubMed DOI PMC

Ozsoy O, Seval-Celik Y, Hacioglu G, Yargicoglu P, Demir R, Agar A, et al. The influence and the mechanism of docosahexaenoic acid on a mouse model of Parkinson’s disease. Neurochem Int. 2011;59(5):664–670. doi: 10.1016/j.neuint.2011.06.012. PubMed DOI

Pomponi M, Loria G, Salvati S, Di Biase A, Conte G, Villella C, et al. DHA effects in Parkinson disease depression. Basal Ganglia. 2014;4(2):61–66. doi: 10.1016/j.baga.2014.03.004. DOI

da Silva TM, Munhoz RP, Alvarez C, Naliwaiko K, Kiss A, Andreatini R, et al. Depression in Parkinson’s disease: a double-blind, randomized, placebo-controlled pilot study of omega-3 fatty-acid supplementation. J Affect Disord. 2008;111(2–3):351–359. doi: 10.1016/j.jad.2008.03.008. PubMed DOI

Darios F, Davletov B. Omega-3 and omega-6 fatty acids stimulate cell membrane expansion by acting on syntaxin 3. Nature. 2006;440(7085):813–817. doi: 10.1038/nature04598. PubMed DOI

Chytrova G, Ying Z, Gomez-Pinilla F. Exercise contributes to the effects of DHA dietary supplementation by acting on membrane-related synaptic systems. Brain Res. 2010;1341:32–40. doi: 10.1016/j.brainres.2009.05.018. PubMed DOI PMC

Alessandri J-M, Guesnet P, Vancassel S, Astorg P, Denis I, Langelier B, et al. Polyunsaturated fatty acids in the central nervous system: evolution of concepts and nutritional implications throughout life. Reprod Nutr Dev. 2004;44(6):509–538. doi: 10.1051/rnd:2004063. PubMed DOI

Arima H, Omura T, Hayasaka T, Masaki N, Hanada M, Xu D, et al. Reductions of docosahexaenoic acid-containing phosphatidylcholine levels in the anterior horn of and ALS mouse model. Neuroscience. 2015;297:127–136. doi: 10.1016/j.neuroscience.2015.03.060. PubMed DOI

Ilieva EV, Ayala V, Jové M, Dalfó E, Cacabelos D, Povedano M, et al. Oxidative and endoplasmic reticulum stress interplay in sporadic amyotrophic lateral sclerosis. Brain. 2007;130(12):3111–3123. doi: 10.1093/brain/awm190. PubMed DOI

Ayala V, Granado-Serrano AB, Cacabelos D, Naudi A, Ilieva EV, Boada J, et al. Cell stress induces TDP-43 pathological changes associated with ERK1/2 dysfunction: implications in ALS. Acta Neuropathol. 2011;122(3):259–270. doi: 10.1007/s00401-011-0850-y. PubMed DOI

Cacabelos D, Ayala V, Granado-Serrano AB, Jove M, Torres P, Boada J, et al. Interplay between TDP-43 and docosahexaenoic acid-related processes in amyotrophic lateral sclerosis. Neurobiol Dis. 2016;88:148–160. doi: 10.1016/j.nbd.2016.01.007. PubMed DOI

Fitzgerald KC, O’Reilly ÉJ, Falcone GJ, et al. Dietary ω-3 polyunsaturated fatty acid intake and risk for amyotrophic lateral sclerosis. JAMA Neurol. 2014;71(9):1102–1110. doi: 10.1001/jamaneurol.2014.1214. PubMed DOI PMC

Pettit LK, Varsanyi C, Tadros J, Vassiliou E. Modulating the inflammatory properties of activated microglia with docosahexaenoic acid and aspirin. Lipids Health Dis. 2013;12:16. doi: 10.1186/1476-511X-12-16. PubMed DOI PMC

Yip PK, Pizzasegola C, Gladman S, Biggio ML, Marino M, Jayasinghe M, et al. The omega-3 fatty acid eicosapentaenoic acid accelerates disease progression in a model of amyotrophic lateral sclerosis. PLoS ONE. 2013;8:17. PubMed PMC

Shibata N, Yamada S, Uchida K, Hirano A, Sakoda S, Fujimura H, et al. Accumulation of protein-bound 4-hydroxy-2-hexenal in spinal cords from patients with sporadic amyotrophic lateral sclerosis. Brain Res. 2004;1019(1–2):170–177. doi: 10.1016/j.brainres.2004.05.110. PubMed DOI

Siriwardhana N, Kalupahana NS, Moustaid-Moussa N. Health benefits of n-3 polyunsaturated fatty acids: eicosapentaenoic acid and docosahexaenoic acid. In: Kim SK, editor. Advances in food and nutrition research, vol 65 implications and applications—animals and microbes. San Diego: Elsevier Academic Press Inc; 2012. pp. 211–222. PubMed

Hussein JS. Cell membrane fatty acids and health. Int J Pharm Pharm Sci. 2013;5(3):38–46.

Simopoulos AP. Dietary omega-3 fatty acid deficiency and high fructose intake in the development of metabolic syndrome, brain metabolic abnormalities, and non-alcoholic fatty liver disease. Nutrients. 2013;5(8):2901–2923. doi: 10.3390/nu5082901. PubMed DOI PMC

Fritsche KL. The science of fatty acids and inflammation. Adv Nutr. 2015;6(3):293S–301S. doi: 10.3945/an.114.006940. PubMed DOI PMC

Domenichiello AF, Kitson AP, Bazinet RP. Is docosahexaenoic acid synthesis from a-linolenic acid sufficient to supply the adult brain? Prog Lipid Res. 2015;59:54–66. doi: 10.1016/j.plipres.2015.04.002. PubMed DOI

Global Organization for EPA and DHA Omega-3s (2015) Global recommendations for EPA and DHA intake. p. 17

FAO Fats and fatty acids in human nutrition. Report of an expert consultation. FAO Food Nutr Pap. 2010;1:1–166. PubMed

Authority EFS Scientific opinion on dietary reference values for fats, including saturated fatty acids, polyunsaturated fatty acids, monounsaturated fatty acids, trans fatty acids, and cholesterol. EFSA J. 2010;8(3):1461. doi: 10.2903/j.efsa.2010.1461. DOI

Kus-Yamashita MMM, Mcdonald B, Ravacci G, Rogero MM, Santos RD, Waitzberg D, et al. Polyunsaturated fatty acids: health impacts. Eur J Nutr Food Saf. 2016;6(3):111–131. doi: 10.9734/EJNFS/2016/23018. DOI

Jensen CL. Effects of n-3 fatty acids during pregnancy and lactation. Am J Clin Nutr. 2006;83(Suppl):1452–1457. PubMed

Koletzko B, Cetin I, Brenna JT, Grp P. Dietary fat intakes for pregnant and lactating women. Br J Nutr. 2007;98(5):873–877. doi: 10.1017/S0007114507764747. PubMed DOI

Morgese M, Trabace L. Maternal malnutrition in the etiopathogenesis of psychiatric diseases: role of polyunsaturated fatty acids. Brain Sci. 2016;6(3):24. doi: 10.3390/brainsci6030024. PubMed DOI PMC

Sanders TAB, Reddy S. The influence of a vegetarian diet on the fatty-acid composition of human-milk and the essential fatty-acid status of the infant. J Pediatr. 1992;120(Suppl):71–77. doi: 10.1016/S0022-3476(05)81239-9. PubMed DOI

The State of World Fisheries and Aquaculture (2016) Contributing to food security and nutrition for all. FAO

Zárate R, el Jaber-Vazdekis N, Ramírez-Moreno R. Importance of polyunsaturated fatty acids from marine algae. In: Hegde MV, Zanwar AA, Adekar SP, editors. Omega-3 fatty acids: keys to nutritional health. Cham: Springer International Publishing; 2016. pp. 101–126.

Microelements, Fatty Acid Profile, and Selected Biomarkers in Grass Carp (Ctenopharyngodon idella) Muscle Tissue: Seasonal Variations and Health Risk Assessment

Marine microalgae Schizochytrium demonstrates strong production of essential fatty acids in various cultivation conditions, advancing dietary self-sufficiency

Dietary n-3/n-6 polyunsaturated fatty acid ratio modulates growth performance in spotted seabass (Lateolabrax maculatus) through regulating lipid metabolism, hepatic antioxidant capacity and intestinal health

The fatty acid composition of serum phospholipids in adolescents is associated with body composition in early adulthoods: an eight-year follow-up study

Partial fads2 Gene Knockout Diverts LC-PUFA Biosynthesis via an Alternative Δ8 Pathway with an Impact on the Reproduction of Female Zebrafish (Danio rerio)

Potential of Nanonutraceuticals in Increasing Immunity

Negative Energy Balance Influences Nutritional Quality of Milk from Czech Fleckvieh Cows due Changes in Proportion of Fatty Acids

Assessment of Fatty Acid Desaturase (Fads2) Structure-Function Properties in Fish in the Context of Environmental Adaptations and as a Target for Genetic Engineering