Journal of Physiology and Biochemistry

, Volume 71, Issue 2, pp 341–349 | Cite as

An update on the role of omega-3 fatty acids on inflammatory and degenerative diseases

  • Silvia Lorente-Cebrián
  • André G. V. Costa
  • Santiago Navas-Carretero
  • María Zabala
  • Laura M. Laiglesia
  • J. Alfredo Martínez
  • María J. Moreno-AliagaEmail author
Mini Review


Inflammation is involved in the pathophysiology of many chronic diseases, such as rheumatoid arthritis and neurodegenerative diseases. Several studies have evidenced important anti-inflammatory and immunomodulatory properties of omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs). This review illustrates current knowledge about the efficacy of n-3 LC-PUFAs (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), particularly) in preventing and/or treating several chronic inflammatory conditions (inflammatory bowel diseases and rheumatoid arthritis) as well as their potential benefits on neurodegenerative diseases. It is well established that n-3 LC-PUFAs are substrates for synthesis of novel series of lipid mediators (e.g., resolvins, protectins, and maresins) with potent anti-inflammatory and pro-resolving properties, which have been proposed to partly mediate the protective and beneficial actions of n-3 LC-PUFAs. Here, we briefly summarize current knowledge from preclinical studies analyzing the actions of EPA- and DHA-derived resolvins and protectins on pathophysiological models of rheumatoid arthritis, Alzheimer, and irritable bowel syndrome.


Omega-3 n-3 LC-PUFAs Inflammatory diseases Neurodegenerative diseases 


Conflict of interest



  1. 1.
    Adam O, Beringer C, Kless T, Lemmen C, Adam A, Wiseman M, Adam P, Klimmek R, Forth W (2003) Anti-inflammatory effects of a low arachidonic acid diet and fish oil in patients with rheumatoid arthritis. Rheumatol Int 23:27–36PubMedGoogle Scholar
  2. 2.
    Akabas SR, Deckelbaum RJ (2006) Summary of a workshop on n-3 fatty acids: current status of recommendations and future directions. Am J Clin Nutr 83:1536S–1538SPubMedGoogle Scholar
  3. 3.
    Almallah YZ, Richardson S, O’Hanrahan T, Mowat NA, Brunt PW, Sinclair TS, Ewen S, Heys SD, Eremin O (1998) Distal procto-colitis, natural cytotoxicity, and essential fatty acids. Am J Gastroenterol 93:804–809CrossRefPubMedGoogle Scholar
  4. 4.
    Arita M, Yoshida M, Hong S, Tjonahen E, Glickman JN, Petasis NA, Blumberg RS, Serhan CN (2005) Resolvin E1, an endogenous lipid mediator derived from omega-3 eicosapentaenoic acid, protects against 2,4,6-trinitrobenzene sulfonic acid-induced colitis. Proc Natl Acad Sci U S A 102:7671–7676CrossRefPubMedCentralPubMedGoogle Scholar
  5. 5.
    Barberger-Gateau P, Raffaitin C, Letenneur L, Berr C, Tzourio C, Dartigues JF, Alperovitch A (2007) Dietary patterns and risk of dementia: the Three-City cohort study. Neurology 69:1921–1930CrossRefPubMedGoogle Scholar
  6. 6.
    Bazan NG (2009) Neuroprotectin D1-mediated anti-inflammatory and survival signaling in stroke, retinal degenerations, and Alzheimer’s disease. J Lipid Res 50(Suppl):S400–S405PubMedCentralPubMedGoogle Scholar
  7. 7.
    Belluzzi A, Brignola C, Campieri M, Pera A, Boschi S, Miglioli M (1996) Effect of an enteric-coated fish-oil preparation on relapses in Crohn’s disease. N Engl J Med 334:1557–1560CrossRefPubMedGoogle Scholar
  8. 8.
    Bento AF, Marcon R, Dutra RC, Claudino RF, Cola M, Leite DF, Calixto JB (2011) Beta-caryophyllene inhibits dextran sulfate sodium-induced colitis in mice through CB2 receptor activation and PPARgamma pathway. Am J Pathol 178:1153–1166CrossRefPubMedCentralPubMedGoogle Scholar
  9. 9.
    Berbert AA, Kondo CR, Almendra CL, Matsuo T, Dichi I (2005) Supplementation of fish oil and olive oil in patients with rheumatoid arthritis. Nutrition 21:131–136CrossRefPubMedGoogle Scholar
  10. 10.
    Beydoun MA, Kaufman JS, Satia JA, Rosamond W, Folsom AR (2007) Plasma n-3 fatty acids and the risk of cognitive decline in older adults: the Atherosclerosis Risk in Communities Study. Am J Clin Nutr 85:1103–1111PubMedGoogle Scholar
  11. 11.
    Calder PC (2006) n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr 83:1505S–1519SPubMedGoogle Scholar
  12. 12.
    Calder PC (2008) Polyunsaturated fatty acids, inflammatory processes and inflammatory bowel diseases. Mol Nutr Food Res 52:885–897CrossRefPubMedGoogle Scholar
  13. 13.
    Calder PC (2014) Marine omega-3 fatty acids and inflammatory processes: effects, mechanisms and clinical relevance. Biochim Biophys Acta 1851(4):469–484CrossRefPubMedGoogle Scholar
  14. 14.
    Connor WE, Connor SL (2007) The importance of fish and docosahexaenoic acid in Alzheimer disease. Am J Clin Nutr 85:929–930PubMedGoogle Scholar
  15. 15.
    Dichi I, Frenhane P, Dichi JB, Correa CR, Angeleli AY, Bicudo MH, Rodrigues MA, Victoria CR, Burini RC (2000) Comparison of omega-3 fatty acids and sulfasalazine in ulcerative colitis. Nutrition 16:87–90CrossRefPubMedGoogle Scholar
  16. 16.
    Dullemeijer C, Durga J, Brouwer IA, van de Rest O, Kok FJ, Brummer RJ, van Boxtel MP, Verhoef P (2007) n 3 fatty acid proportions in plasma and cognitive performance in older adults. Am J Clin Nutr 86:1479–1485PubMedGoogle Scholar
  17. 17.
    Feagan BG, Sandborn WJ, Mittmann U, Bar-Meir S, D’Haens G, Bradette M, Cohen A, Dallaire C, Ponich TP, McDonald JW, Hebuterne X, Pare P, Klvana P, Niv Y, Ardizzone S, Alexeeva O, Rostom A, Kiudelis G, Spleiss J, Gilgen D, Vandervoort MK, Wong CJ, Zou GY, Donner A, Rutgeerts P (2008) Omega-3 free fatty acids for the maintenance of remission in Crohn disease: the EPIC Randomized Controlled Trials. JAMA 299:1690–1697CrossRefPubMedGoogle Scholar
  18. 18.
    Feart C, Peuchant E, Letenneur L, Samieri C, Montagnier D, Fourrier-Reglat A, Barberger-Gateau P (2008) Plasma eicosapentaenoic acid is inversely associated with severity of depressive symptomatology in the elderly: data from the Bordeaux sample of the Three-City Study. Am J Clin Nutr 87:1156–1162PubMedGoogle Scholar
  19. 19.
    Freund Levi Y, Vedin I, Cederholm T, Basun H, Faxen Irving G, Eriksdotter M, Hjorth E, Schultzberg M, Vessby B, Wahlund LO, Salem N Jr, Palmblad J (2014) Transfer of omega-3 fatty acids across the blood-brain barrier after dietary supplementation with a docosahexaenoic acid-rich omega-3 fatty acid preparation in patients with Alzheimer’s disease: the OmegAD study. J Intern Med 275:428–436CrossRefPubMedGoogle Scholar
  20. 20.
    Freund-Levi Y, Eriksdotter-Jonhagen M, Cederholm T, Basun H, Faxen-Irving G, Garlind A, Vedin I, Vessby B, Wahlund LO, Palmblad J (2006) Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: a randomized double-blind trial. Arch Neurol 63:1402–1408CrossRefPubMedGoogle Scholar
  21. 21.
    Freund-Levi Y, Vedin I, Hjorth E, Basun H, Faxen Irving G, Schultzberg M, Eriksdotter M, Palmblad J, Vessby B, Wahlund LO, Cederholm T, Basu S (2014) Effects of supplementation with omega-3 fatty acids on oxidative stress and inflammation in patients with Alzheimer’s disease: the OmegAD study. J Alzheimers Dis 42:823–831PubMedGoogle Scholar
  22. 22.
    Galarraga B, Ho M, Youssef HM, Hill A, McMahon H, Hall C, Ogston S, Nuki G, Belch JJ (2008) Cod liver oil (n-3 fatty acids) as an non-steroidal anti-inflammatory drug sparing agent in rheumatoid arthritis. Rheumatology (Oxford) 47:665–669CrossRefGoogle Scholar
  23. 23.
    Grogan JL, Casson DH, Terry A, Burdge GC, El-Matary W, Dalzell AM (2012) Enteral feeding therapy for newly diagnosed pediatric Crohn’s disease: a double-blind randomized controlled trial with two years follow-up. Inflamm Bowel Dis 18:246–253CrossRefPubMedGoogle Scholar
  24. 24.
    Hedin CR, Mullard M, Sharratt E, Jansen C, Sanderson JD, Shirlaw P, Howe LC, Djemal S, Stagg AJ, Lindsay JO, Whelan K (2010) Probiotic and prebiotic use in patients with inflammatory bowel disease: a case-control study. Inflamm Bowel Dis 16:2099–2108CrossRefPubMedGoogle Scholar
  25. 25.
    Ishida T, Yoshida M, Arita M, Nishitani Y, Nishiumi S, Masuda A, Mizuno S, Takagawa T, Morita Y, Kutsumi H, Inokuchi H, Serhan CN, Blumberg RS, Azuma T (2010) Resolvin E1, an endogenous lipid mediator derived from eicosapentaenoic acid, prevents dextran sulfate sodium-induced colitis. Inflamm Bowel Dis 16:87–95CrossRefPubMedCentralPubMedGoogle Scholar
  26. 26.
    Jazayeri S, Tehrani-Doost M, Keshavarz SA, Hosseini M, Djazayery A, Amini H, Jalali M, Peet M (2008) Comparison of therapeutic effects of omega-3 fatty acid eicosapentaenoic acid and fluoxetine, separately and in combination, in major depressive disorder. Aust N Z J Psychiatry 42:192–198CrossRefPubMedGoogle Scholar
  27. 27.
    Ji RR, Xu ZZ, Strichartz G, Serhan CN (2011) Emerging roles of resolvins in the resolution of inflammation and pain. Trends Neurosci 34:599–609CrossRefPubMedCentralPubMedGoogle Scholar
  28. 28.
    John S, Luben R, Shrestha SS, Welch A, Khaw KT, Hart AR (2010) Dietary n-3 polyunsaturated fatty acids and the aetiology of ulcerative colitis: a UK prospective cohort study. Eur J Gastroenterol Hepatol 22:602–606CrossRefPubMedGoogle Scholar
  29. 29.
    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 69:217–224CrossRefPubMedCentralPubMedGoogle Scholar
  30. 30.
    Kremer JM, Bigauoette J, Michalek AV, Timchalk MA, Lininger L, Rynes RI, Huyck C, Zieminski J, Bartholomew LE (1985) Effects of manipulation of dietary fatty acids on clinical manifestations of rheumatoid arthritis. Lancet 1:184–187CrossRefPubMedGoogle Scholar
  31. 31.
    Lee TK, Clandinin MT, Hebert M, MacDonald IM (2010) Effect of docosahexaenoic acid supplementation on the macular function of patients with Best vitelliform macular dystrophy: randomized clinical trial. Can J Ophthalmol 45:514–519CrossRefPubMedGoogle Scholar
  32. 32.
    MacLean CH, Mojica WA, Morton SC, Pencharz J, Hasenfeld Garland R, Tu W, Newberry SJ, Jungvig LK, Grossman J, Khanna P, Rhodes S and Shekelle P (2004) Effects of omega-3 fatty acids on lipids and glycemic control in type II diabetes and the metabolic syndrome and on inflammatory bowel disease, rheumatoid arthritis, renal disease, systemic lupus erythematosus, and osteoporosis. Evid Rep Technol Assess (Summ):1–4Google Scholar
  33. 33.
    Marcon R, Bento AF, Dutra RC, Bicca MA, Leite DF, Calixto JB (2013) Maresin 1, a proresolving lipid mediator derived from omega-3 polyunsaturated fatty acids, exerts protective actions in murine models of colitis. J Immunol 191:4288–4298CrossRefPubMedGoogle Scholar
  34. 34.
    Middleton SJ, Naylor S, Woolner J, Hunter JO (2002) A double-blind, randomized, placebo-controlled trial of essential fatty acid supplementation in the maintenance of remission of ulcerative colitis. Aliment Pharmacol Ther 16:1131–1135CrossRefPubMedGoogle Scholar
  35. 35.
    Mizwicki MT, Liu G, Fiala M, Magpantay L, Sayre J, Siani A, Mahanian M, Weitzman R, Hayden EY, Rosenthal MJ, Nemere I, Ringman J, Teplow DB (2013) 1alpha,25-dihydroxyvitamin D3 and resolvin D1 retune the balance between amyloid-beta phagocytosis and inflammation in Alzheimer’s disease patients. J Alzheimers Dis 34:155–170PubMedCentralPubMedGoogle Scholar
  36. 36.
    Nurk E, Drevon CA, Refsum H, Solvoll K, Vollset SE, Nygard O, Nygaard HA, Engedal K, Tell GS, Smith AD (2007) Cognitive performance among the elderly and dietary fish intake: the Hordaland Health Study. Am J Clin Nutr 86:1470–1478PubMedGoogle Scholar
  37. 37.
    Peyrin-Biroulet L, Beisner J, Wang G, Nuding S, Oommen ST, Kelly D, Parmentier-Decrucq E, Dessein R, Merour E, Chavatte P, Grandjean T, Bressenot A, Desreumaux P, Colombel JF, Desvergne B, Stange EF, Wehkamp J, Chamaillard M (2010) Peroxisome proliferator-activated receptor gamma activation is required for maintenance of innate antimicrobial immunity in the colon. Proc Natl Acad Sci U S A 107:8772–8777CrossRefPubMedCentralPubMedGoogle Scholar
  38. 38.
    Quinn JF, Raman R, Thomas RG, Yurko-Mauro K, Nelson EB, Van Dyck C, Galvin JE, Emond J, Jack CR Jr, Weiner M, Shinto L, Aisen PS (2010) Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: a randomized trial. JAMA 304:1903–1911CrossRefPubMedCentralPubMedGoogle Scholar
  39. 39.
    Remans PH, Sont JK, Wagenaar LW, Wouters-Wesseling W, Zuijderduin WM, Jongma A, Breedveld FC, Van Laar JM (2004) Nutrient supplementation with polyunsaturated fatty acids and micronutrients in rheumatoid arthritis: clinical and biochemical effects. Eur J Clin Nutr 58:839–845CrossRefPubMedGoogle Scholar
  40. 40.
    Rondanelli M, Giacosa A, Opizzi A, Pelucchi C, La Vecchia C, Montorfano G, Negroni M, Berra B, Politi P, Rizzo AM (2011) Long chain omega 3 polyunsaturated fatty acids supplementation in the treatment of elderly depression: effects on depressive symptoms, on phospholipids fatty acids profile and on health-related quality of life. J Nutr Health Aging 15:37–44CrossRefPubMedGoogle Scholar
  41. 41.
    Samieri C, Feart C, Letenneur L, Dartigues JF, Peres K, Auriacombe S, Peuchant E, Delcourt C, Barberger-Gateau P (2008) Low plasma eicosapentaenoic acid and depressive symptomatology are independent predictors of dementia risk. Am J Clin Nutr 88:714–721PubMedGoogle Scholar
  42. 42.
    SanGiovanni JP, Chew EY, Agron E, Clemons TE, Ferris FL 3rd, Gensler G, Lindblad AS, Milton RC, Seddon JM, Klein R, Sperduto RD (2008) The relationship of dietary omega-3 long-chain polyunsaturated fatty acid intake with incident age-related macular degeneration: AREDS report no. 23. Arch Ophthalmol 126:1274–1279CrossRefPubMedCentralPubMedGoogle Scholar
  43. 43.
    Serhan CN, Arita M, Hong S, Gotlinger K (2004) Resolvins, docosatrienes, and neuroprotectins, novel omega-3-derived mediators, and their endogenous aspirin-triggered epimers. Lipids 39:1125–1132CrossRefPubMedGoogle Scholar
  44. 44.
    Shinto L, Quinn J, Montine T, Dodge HH, Woodward W, Baldauf-Wagner S, Waichunas D, Bumgarner L, Bourdette D, Silbert L, Kaye J (2014) A randomized placebo-controlled pilot trial of omega-3 fatty acids and alpha lipoic acid in Alzheimer’s disease. J Alzheimers Dis 38:111–120PubMedGoogle Scholar
  45. 45.
    Sinn N, Bryan J, Wilson C (2008) Cognitive effects of polyunsaturated fatty acids in children with attention deficit hyperactivity disorder symptoms: a randomised controlled trial. Prostaglandins Leukot Essent Fatty Acids 78:311–326CrossRefPubMedGoogle Scholar
  46. 46.
    Sinn N, Milte CM, Street SJ, Buckley JD, Coates AM, Petkov J, Howe PR (2012) Effects of n-3 fatty acids, EPA v. DHA, on depressive symptoms, quality of life, memory and executive function in older adults with mild cognitive impairment: a 6-month randomised controlled trial. Br J Nutr 107:1682–1693CrossRefPubMedGoogle Scholar
  47. 47.
    Sperling RI, Weinblatt M, Robin JL, Ravalese J 3rd, Hoover RL, House F, Coblyn JS, Fraser PA, Spur BW, Robinson DR et al (1987) Effects of dietary supplementation with marine fish oil on leukocyte lipid mediator generation and function in rheumatoid arthritis. Arthritis Rheum 30:988–997CrossRefPubMedGoogle Scholar
  48. 48.
    Stafford MR, Jackson H, Mayo-Wilson E, Morrison AP, Kendall T (2013) Early interventions to prevent psychosis: systematic review and meta-analysis. BMJ 346:f185CrossRefPubMedCentralPubMedGoogle Scholar
  49. 49.
    Sydenham E, Dangour AD, Lim WS (2012) Omega 3 fatty acid for the prevention of cognitive decline and dementia. Cochrane Database Syst Rev 6:CD005379PubMedGoogle Scholar
  50. 50.
    Turner D, Shah PS, Steinhart AH, Zlotkin S, Griffiths AM (2011) Maintenance of remission in inflammatory bowel disease using omega-3 fatty acids (fish oil): a systematic review and meta-analyses. Inflamm Bowel Dis 17:336–345CrossRefPubMedGoogle Scholar
  51. 51.
    van Gelder BM, Tijhuis M, Kalmijn S, Kromhout D (2007) Fish consumption, n-3 fatty acids, and subsequent 5-y cognitive decline in elderly men: the Zutphen Elderly Study. Am J Clin Nutr 85:1142–1147PubMedGoogle Scholar
  52. 52.
    Volker D, Fitzgerald P, Major G, Garg M (2000) Efficacy of fish oil concentrate in the treatment of rheumatoid arthritis. J Rheumatol 27:2343–2346PubMedGoogle Scholar
  53. 53.
    Zhao Y, Calon F, Julien C, Winkler JW, Petasis NA, Lukiw WJ, Bazan NG (2011) Docosahexaenoic acid-derived neuroprotectin D1 induces neuronal survival via secretase- and PPARgamma-mediated mechanisms in Alzheimer’s disease models. PLoS One 6:e15816CrossRefPubMedCentralPubMedGoogle Scholar

Copyright information

© University of Navarra 2015

Authors and Affiliations

  • Silvia Lorente-Cebrián
    • 1
  • André G. V. Costa
    • 1
    • 2
  • Santiago Navas-Carretero
    • 1
    • 3
  • María Zabala
    • 1
  • Laura M. Laiglesia
    • 1
  • J. Alfredo Martínez
    • 1
    • 3
  • María J. Moreno-Aliaga
    • 1
    • 3
    Email author
  1. 1.Department of Nutrition, Food Science and Physiology and Center for Nutrition ResearchUniversity of NavarraPamplonaSpain
  2. 2.Department of Pharmacy and Nutrition, Center for Agrarian SciencesFederal University of Espírito SantoAlegreBrazil
  3. 3.CIBERobn Physiopathology of Obesity and NutritionMadridSpain

Personalised recommendations