Clinical Oral Investigations

, Volume 20, Issue 5, pp 879–894 | Cite as

Omega-3 fatty acids as an adjunct for periodontal therapy—a review

  • B. Chee
  • B. Park
  • T. Fitzsimmons
  • A. M. Coates
  • P. M. Bartold



The aim of this article is to present an overview of omega-3 fatty acids, their anti-inflammatory properties and potential use as an adjunct for periodontal therapy.

Materials and methods

A general literature search was conducted to provide an overview of omega-3 fatty acids, their metabolism and anti-inflammatory properties. A more specific literature search of PubMed and EMBASE was conducted to identify articles dealing studies investigating the effects of omega-3 fatty acids in the treatment of periodontitis in animals and humans and included cross-sectional, longitudinal and intervention designs.


To date, there is good emerging evidence that dietary supplementation with fish oil may be of some benefit and this is enhanced if combined with aspirin. All clinical intervention studies to date have been on small sample sizes, and this indicates there is need for larger and more robust clinical trials to verify these initial findings.


Dietary supplementation with fish oil could be a cost-effective adjunctive therapy to the management of periodontal disease.

Clinical relevance

The host modulatory properties of omega-3 fatty acids warrant further assessment of their use as an adjunct in the management of periodontitis.


Omega-3 fatty acids Periodontitis Host response 


  1. 1.
    Eke PI, Dye BA, Wei L, Thornton-Evans GO, Genco RJ (2012) Prevalence of periodontitis in adults in the United States: 2009 and 2010. J Dent Res 91:914–920PubMedCrossRefGoogle Scholar
  2. 2.
    Löe H, Thielade E, Jensen SB (1965) Experimental gingivitis in man. J Periodontol 36:177–187PubMedCrossRefGoogle Scholar
  3. 3.
    Salvi GE, Lang NP (2005) Host response modulation in the management of periodontal diseases. J Clin Periodontol 32(Suppl 6):108–129PubMedCrossRefGoogle Scholar
  4. 4.
    Williams RC (2008) Host modulation for the treatment of periodontal disease. Compend Contin Educ Dent 29:160–162, 164, 166–168 PubMedGoogle Scholar
  5. 5.
    Bhatavadekar NB, Williams RC (2009) New directions in host modulation for the management of periodontal disease. J Clin Periodontol 36:124–126PubMedCrossRefGoogle Scholar
  6. 6.
    Kornman KS (2008) Mapping the pathogenesis of periodontitis: a new look. J Periodontol 79:1560–1568PubMedCrossRefGoogle Scholar
  7. 7.
    Preshaw PM, Taylor J (2011) How has research into cytokine interactions and their role in driving immune responses impacted our understanding of periodontitis? J Clin Periodontol 38:60–84PubMedCrossRefGoogle Scholar
  8. 8.
    Bartold PM, Walsh LJ, Narayanan AS (2000) Molecular and cell biology of the gingiva. Periodontol 2000 24:28–55PubMedCrossRefGoogle Scholar
  9. 9.
    Page RC, Offenbacher S, Schroeder HE, Seymour GJ, Kornman KS (1997) Advances in the pathogenesis of periodontitis: summary of developments, clinical implications and future directions. Periodontol 2000 14:216–248PubMedCrossRefGoogle Scholar
  10. 10.
    Kantarci A, Oyaizu K, Van Dyke TE (2003) Neutrophil-mediated tissue injury in periodontal disease pathogenesis: findings from localized aggressive periodontitis. J Periodontol 74:66–75PubMedCrossRefGoogle Scholar
  11. 11.
    Page RC, Schroeder HE (1976) Pathogenesis of inflammatory periodontal disease. A summary of current work. Lab Investig 34:235–249PubMedGoogle Scholar
  12. 12.
    Kornman KS, Page RC, Tonetti MS (1997) The host response to the microbial challenge in periodontitis: assembling the players. Periodontol 2000 14:33–53PubMedCrossRefGoogle Scholar
  13. 13.
    Nussbaum G, Shapira L (2011) How has neutrophil research improved our understanding of periodontal pathogenesis? J Clin Periodontol 38:49–59PubMedCrossRefGoogle Scholar
  14. 14.
    Sorsa T, Tjäderhane L, Konttinen YT, Lauhio A, Salo T, Lee HM, Golub LM, Brown DL, Mantyla P (2006) Matrix metalloproteinases: contribution to pathogenesis, diagnosis and treatment of periodontal inflammation. Ann Med 38:306–321PubMedCrossRefGoogle Scholar
  15. 15.
    Silva TA, Garlet GP, Fukada SY, Silva JS, Cunha FQ (2007) Chemokines in oral inflammatory diseases: apical periodontitis and periodontal disease. J Dent Res 86:306–319PubMedCrossRefGoogle Scholar
  16. 16.
    Gemmell E, Seymour GJ (2004) Immunoregulatory control of Th1/Th2 cytokine profiles in periodontal disease. Periodontol 2000 35:21–41PubMedCrossRefGoogle Scholar
  17. 17.
    Das UN (2013) Lipoxins, resolvins, protectins, maresins and nitrolipids, and their clinical implications with specific reference to diabetes mellitus and other diseases: part II. J Clin Lipidol 8:465–480CrossRefGoogle Scholar
  18. 18.
    Cobb CM, Jeffcoat MK (2002) Clinical significance of non-surgical periodontal therapy: an evidence-based perspective of scaling and root planing. J Clin Periodontol 29:6–16PubMedCrossRefGoogle Scholar
  19. 19.
    Hirschfeld L, Wasserman B (1978) A long-term survey of tooth loss in 600 treated periodontal patients. J Periodontol 49:225–237PubMedCrossRefGoogle Scholar
  20. 20.
    Renvert S, Wikstrom M, Dahlen G, Slots J, Egelberg J (1990) On the inability of root debridement and periodontal surgery to eliminate Actinobacillus actinomycetemcomitans from periodontal pockets. J Clin Periodontol 17:351–355PubMedCrossRefGoogle Scholar
  21. 21.
    Haffajee AD, Cugini MA, Dibart S, Smith C, Kent RL Jr, Socransky SS (1997) The effect of SRP on the clinical and microbiological parameters of periodontal diseases. J Clin Periodontol 24:324–334PubMedCrossRefGoogle Scholar
  22. 22.
    Haffajee AD, Teles RP, Socransky SS (2006) The effect of periodontal therapy on the composition of the subgingival microbiota. Periodontol 2000 42:219–258PubMedCrossRefGoogle Scholar
  23. 23.
    Magnusson I, Lindhe J, Yoneyama T, Liljenberg B (1984) Recolonization of a subgingival microbiota following scaling in deep pockets. J Clin Periodontol 11:193–207PubMedCrossRefGoogle Scholar
  24. 24.
    Axelsson P, Lindhe J (1981) The significance of maintenance care in the treatment of periodontal disease. J Clin Periodontol 8:281–294PubMedCrossRefGoogle Scholar
  25. 25.
    Lindhe J, Nyman S (1984) Long-term maintenance of patients treated for advanced periodontal disease. J Clin Periodontol 11:504–514PubMedCrossRefGoogle Scholar
  26. 26.
    Axelsson P, Nyström B, Lindhe J (2004) The long-term effect of a plaque control program on tooth mortality, caries and periodontal disease in adults. J Clin Periodontol 31:749–757PubMedCrossRefGoogle Scholar
  27. 27.
    Preshaw PM (2008) Host response modulation in periodontics. Periodontol 2000 48:92–110PubMedCrossRefGoogle Scholar
  28. 28.
    Nyman S, Schroeder HE, Lindhe J (1979) Suppression of inflammation and bone resorption by indomethacin during experimental periodontitis in dogs. J Periodontol 50:450–461PubMedCrossRefGoogle Scholar
  29. 29.
    Williams RC, Offenbacher S, Jeffcoat MK, Howell TH, Johnson HG, Hall CM, Wechter WJ, Goldhaber P (1988) Indomethacin or flurbiprofen treatment of periodontitis in beagles: effect on crevicular fluid arachidonic acid metabolites compared with effect on alveolar bone loss. J Periodontal Res 23:134–138PubMedCrossRefGoogle Scholar
  30. 30.
    Howell TH, Jefficoat MK, Goldhaber P, Reddy MS, Kaplan ML, Johnson HG, Hall CM, Williams RC (1991) Inhibition of alveolar bone loss in beagles with the NSAID naproxen. J Periodontal Res 26:498–501PubMedCrossRefGoogle Scholar
  31. 31.
    Offenbacher S, Williams RC, Jeffcoat MK, Howell TH, Odle BM, Smith MA, Hall CM, Johnson HG, Goldhaber P (1992) Effects of NSAID on beagle crevicular cyclooxygenase metabolites and periodontal bone loss. J Periodontal Res 27:207–213PubMedCrossRefGoogle Scholar
  32. 32.
    Waite IM, Saxton CA, Young A, Wagg BJ, Corbett M (1981) The periodontal status of subjects receiving non-steroidal anti-inflammatory drugs. J Periodontal Res 16:100–108PubMedCrossRefGoogle Scholar
  33. 33.
    Williams RC, Jeffcoat MK, Howell TH, Rolla A, Stubbs D, Teoh KW, Reddy MS, Goldhaber P (1989) Altering the progression of human alveolar bone loss with the non-steroidal anti-inflammatory drug flurbiprofen. J Periodontol 60:485–490PubMedCrossRefGoogle Scholar
  34. 34.
    Jeffcoat MK, Page R, Reddy M, Wannawisute A, Waite P, Palcanis K, Cogen R, Williams RC, Basch C (1991) Use of digital radiography to demonstrate the potential of naproxen as an adjunct in the treatment of rapidly progressive periodontitis. J Periodontal Res 26:415–421PubMedCrossRefGoogle Scholar
  35. 35.
    Jeffcoat MK, Reddy MS, Haigh S, Buchanan W, Doyle MJ, Meredith MP, Nelson SL, Goodale MB, Wehmeyer KR (1995) A comparison of topical ketorolac, systemic flurbiprofen, and placebo for the inhibition of bone loss in adult periodontitis. J Periodontol 66:329–338PubMedCrossRefGoogle Scholar
  36. 36.
    Reddy MS, Geurs NC, Gunsolley JC (2003) Periodontal host modulation with antiproteinase, anti-inflammatory, and bone-sparing agents. A systematic review. Ann Periodontol 8:12–37PubMedCrossRefGoogle Scholar
  37. 37.
    Drouganis A, Hirsch R (2001) Low-dose aspirin therapy and periodontal attachment loss in ex- and non-smokers. J Clin Periodontol 28:38–45PubMedCrossRefGoogle Scholar
  38. 38.
    Flemmig TF, Rumetsch M, Klaiber B (1996) Efficacy of systemically administered acetylsalicylic acid plus scaling on periodontal health and elastase-α1-proteinase inhibitor in gingival crevicular fluid. J Clin Periodontol 23:153–159PubMedCrossRefGoogle Scholar
  39. 39.
    Shiloah J, Bland PS, Scarbecz M, Patters MR, Stein SH, Tipton DA (2014) The effect of long-term aspirin intake on the outcome of non-surgical periodontal therapy in smokers: a double-blind, randomized pilot study. J Periodontal Res 49:102–109PubMedCrossRefGoogle Scholar
  40. 40.
    Bezerra MM, De Lima V, Alencar VBM, Vieira IB, Brito GAC, Ribeiro RA, Da Rocha FAC (2000) Selective cyclooxygenase-2 inhibition prevents alveolar bone loss in experimental periodontitis in rats. J Periodontol 71:1009–1014PubMedCrossRefGoogle Scholar
  41. 41.
    Yen CA, Damoulis PD, Stark PC, Hibberd PL, Singh M, Papas AS (2008) The effects of a selective cyclooxgenase-2 inhibitor [celecoxib] on chronic periodontitis. J Periodontol 79:104–113PubMedCrossRefGoogle Scholar
  42. 42.
    Reddy MS, Weatherford Iii TW, Smith CA, West BD, Jeffcoat MK, Jacks TM (1995) Alendronate treatment of naturally-occurring periodontitis in beagle dogs. J Periodontol 66:211–217PubMedCrossRefGoogle Scholar
  43. 43.
    Rocha M, Nava LE, Vazquez de la Torre C, Sanchez-Marin F, Garay-Sevilla ME, Malacara JM (2001) Clinical and radiological improvement of periodontal disease in patients with type 2 diabetes mellitus treated with alendronate: a randomized, placebo-controlled trial. J Periodontol 72:204–209PubMedCrossRefGoogle Scholar
  44. 44.
    Lane N, Armitage GC, Loomer P, Hsieh S, Majumdar S, Wang HY, Jeffcoat M, Munoz T (2005) Bisphosphonate therapy improves the outcome of conventional periodontal treatment: results of a 12-month, randomized, placebo-controlled study. J Periodontol 76:1113–1122PubMedCrossRefGoogle Scholar
  45. 45.
    Saver BG, Hujoel PP, Cunha-Cruz J, Maupomé G (2007) Are statins associated with decreased tooth loss in chronic periodontitis? J Clin Periodontol 34:214–219PubMedCrossRefGoogle Scholar
  46. 46.
    Golub LM, Lee HM, Lehrer G (1983) Minocycline reduces gingival collagenolytic activity during diabetes. Preliminary observations and a proposed new mechanism of action. J Periodontal Res 18:516–526PubMedCrossRefGoogle Scholar
  47. 47.
    Caton JG, Ciancio SG, Blieden TM, Bradshaw M, Crout RJ, Hefti AF, Massaro JM, Polson AM, Thomas J, Walker C (2000) Treatment with subantimicrobial dose doxycycline improves the efficacy of scaling and root planing in patients with adult periodontitis. J Periodontol 71:521–532PubMedCrossRefGoogle Scholar
  48. 48.
    Hirsch R, Deng H, Laohachai MN (2012) Azithromycin in periodontal treatment: more than an antibiotic. J Periodontal Res 47:137–148PubMedCrossRefGoogle Scholar
  49. 49.
    Bartold PM, du Bois AH, Gannon S, Haynes DR, Hirsch RS (2013) Antibacterial and immunomodulatory properties of azithromycin treatment implications for periodontitis. Inflammopharmacol 2:321–338CrossRefGoogle Scholar
  50. 50.
    Yuan H, Gupte R, Zelkha S, Amar S (2011) Receptor activator of nuclear factor kappa B ligand antagonists inhibit tissue inflammation and bone loss in experimental periodontitis. J Clin Periodontol 38:1029–1036PubMedCrossRefGoogle Scholar
  51. 51.
    Assuma R, Oates T, Cochran D, Amar S, Graves DT (1998) IL-1 and TNF antagonists inhibit the inflammatory response and bone loss in experimental periodontitis. J Immunol 160:403–409PubMedGoogle Scholar
  52. 52.
    Delima AJ, Oates T, Assuma R, Schwartz Z, Cochran D, Amar S, Graves DT (2001) Soluble antagonists to interleukin-1 [IL-1] and tumor necrosis factor [TNF] inhibits loss of tissue attachment in experimental periodontitis. J Clin Periodontol 28:233–240PubMedCrossRefGoogle Scholar
  53. 53.
    Ambili R, Santhi WS, Janam P, Nandakumar K, Pillai MR (2005) Expression of activated transcription factor nuclear factor-kappaB in periodontally diseased tissues. J Periodontol 76:1148–1153PubMedCrossRefGoogle Scholar
  54. 54.
    de Souza JAC, Rossa Junior C, Garlet GP, Nogueira AVB, Cirelli JA (2012) Modulation of host cell signaling pathways as a therapeutic approach in periodontal disease. J Appl Oral Sci 20:128–138PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Van Dyke TE (2007) Control of inflammation and periodontitis. Periodontol 2000 45:158–166PubMedCrossRefGoogle Scholar
  56. 56.
    Dawson DR, Branch-Mays G, Gonzalez OA, Ebersole JL (2014) Dietary modulation of the inflammatory cascade. Periodontol 2000 64:161–197PubMedCrossRefGoogle Scholar
  57. 57.
    Silva V, Barazzoni R, Singer P (2014) Biomarkers of fish oil omega-3 polyunsaturated fatty acids intake in humans. Nutr Clin Pract 29:63–72PubMedCrossRefGoogle Scholar
  58. 58.
    Simopoulos AP (2011) Importance of the omega-6/omega-3 balance in health and disease: evolutionary aspects of diet. World Rev Nutr Diet 102:10–21PubMedCrossRefGoogle Scholar
  59. 59.
    James MJ, Gibson RA, Cleland LG (2000) Dietary polyunsaturated fatty acids and inflammatory mediator production. Am J Clin Nutr 71:343S–348SPubMedGoogle Scholar
  60. 60.
    Cleland LG, James MJ, Proudman MS (2005) Fish oil: what the prescriber needs to know. Arthritis Res Ther 8:202PubMedCentralCrossRefGoogle Scholar
  61. 61.
    Yates CM, Calder PC, Ed Rainger G (2014) Pharmacology and therapeutics of omega-3 polyunsaturated fatty acids in chronic inflammatory disease. Pharmacol Ther 141:272–282PubMedCrossRefGoogle Scholar
  62. 62.
    Calder PC (2009) Polyunsaturated fatty acids and inflammatory processes: new twists in an old tale. Biochimie 91:791–795PubMedCrossRefGoogle Scholar
  63. 63.
    Meyer BJ, Mann NJ, Lewis JL, Milligan GC, Sinclair AJ, Howe PR (2003) Dietary intakes and food sources of omega-6 and omega-3 polyunsaturated fatty acids. Lipids 38:391–398PubMedCrossRefGoogle Scholar
  64. 64.
    Sugano M (1996) Characteristics of fats in Japanese diets and current recommendations. Lipids 31(Suppl):S283–S286PubMedCrossRefGoogle Scholar
  65. 65.
    Bang HO, Dyerberg J (1980) The bleeding tendency in Greenland Eskimos. Dan Med Bull 27:202–205PubMedGoogle Scholar
  66. 66.
    Astorg P, Arnault N, Czernichow S, Noisette N, Galan P, Hercberg S (2004) Dietary intakes and food sources of n − 6 and n − 3 PUFA in French adult men and women. Lipids 39:527–535PubMedCrossRefGoogle Scholar
  67. 67.
    Serhan CN (2007) Resolution phase of inflammation: novel endogenous anti-inflammatory and proresolving lipid mediators and pathways. Annu Rev Immunol 25:101–137PubMedCrossRefGoogle Scholar
  68. 68.
    Choi J-S, Park N-H, Hwang S-Y, Jae HS, Kwak I, Choi KK, Choi IS (2013) The antibacterial activity of various saturated and unsaturated fatty acids against several oral pathogens. J Environ Biol 34:673–676PubMedGoogle Scholar
  69. 69.
    Kelley D, Taylor P, Nelson G, Mackey B (1998) Arachidonic acid supplementation enhances synthesis of eicosanoids without suppressing immune functions in young healthy men. Lipids 33:125–130PubMedCrossRefGoogle Scholar
  70. 70.
    Peterson LD, Jeffery NM, Thies F, Sanderson P, Newsholme EA, Calder PC (1998) Eicosapentaenoic and docosahexaenoic acids alter rat spleen leukocyte fatty acid composition and prostaglandin E2 production but have different effects on lymphocyte functions and cell-mediated immunity. Lipids 33:171–180PubMedCrossRefGoogle Scholar
  71. 71.
    Vane JR, Bakhle YS, Botting RM (1998) Cyclooxygenases 1 and 2. Annu Rev Pharmacol Toxicol 38:97–120PubMedCrossRefGoogle Scholar
  72. 72.
    Calder PC (2006) n − 3 Polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr 83:S1505–S1519Google Scholar
  73. 73.
    Bagga D, Wang L, Farias-Eisner R, Glaspy JA, Reddy ST (2003) Differential effects of prostaglandin derived from ω-6 and ω-3 polyunsaturated fatty acids on COX-2 expression and IL-6 secretion. Proc Natl Acad Sci U S A 100:1751–1756PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Calder PC (2013) Omega-3 polyunsaturated fatty acids and inflammatory processes: nutrition or pharmacology? Br J Clin Pharmacol 75:645–662PubMedPubMedCentralGoogle Scholar
  75. 75.
    Tull SP, Yates CM, Maskrey BH, O'Donnell VB, Madden J, Grimble RF, Calder PC, Nash GB, Rainger GE (2009) Omega-3 fatty acids and inflammation: novel interactions reveal a new step in neutrophil recruitment. PLoS Biol 7, e1000177PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Goldman DW, Pickett WC, Goetzl EJ (1983) Human neutrophil chemotactic and degranulating activities of leukotriene B5 [LTB5] derived from eicosapentaenoic acid. Biochem Biophys Res Commun 117:282–288PubMedCrossRefGoogle Scholar
  77. 77.
    Galli C, Passeri G, Macaluso GM (2011) FoxOs, Wnts and oxidative stress-induced bone loss: new players in the periodontitis arena? J Periodontal Res 46:397–406PubMedCrossRefGoogle Scholar
  78. 78.
    Chapple ILC, Matthews JB (2007) The role of reactive oxygen and antioxidant species in periodontal tissue destruction. Periodontol 2000 43:160–232PubMedCrossRefGoogle Scholar
  79. 79.
    Luostarinen R, Saldeen T (1996) Dietary fish oil decreases superoxide generation by human neutrophils: relation to cyclooxygenase pathway and lysosomal enzyme release. Prostaglandins Leukot Essent Fat Acids 55:167–172CrossRefGoogle Scholar
  80. 80.
    Fisher M, Levine PH, Weiner BH, Johnson MH, Doyle EM, Ellis PA, Hoogasian JJ (1990) Dietary n-3 fatty acid supplementation reduces superoxide production and chemiluminescence in a monocyte-enriched preparation of leukocytes. Am J Clin Nutr 51:804–808PubMedGoogle Scholar
  81. 81.
    Healy DA, Wallace FA, Miles EA, Calder PC, Newsholme P (2000) Effect of low-to-moderate amounts of dietary fish oil on neutrophil lipid composition and function. Lipids 35:763–768PubMedCrossRefGoogle Scholar
  82. 82.
    Kew S, Banerjee T, Minihane AM, Finnegan YE, Muggli R, Albers R, Williams CM, Calder PC (2003) Lack of effect of foods enriched with plant- or marine-derived n − 3 fatty acids on human immune function. Am J Clin Nutr 77:1287–1295PubMedGoogle Scholar
  83. 83.
    Endres S, Ghorbani R, Kelley VE, Georgilis K, Lonnemann G, van der Meer JWM, Cannon JG, Rogers TS, Klempner MS, Weber PC, Schaefer EJ, Wolff SM, Dinarello CA (1989) The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells. N Engl J Med 320:265–271PubMedCrossRefGoogle Scholar
  84. 84.
    Caughey GE, Mantzioris E, Gibson RA, Cleland LG, James MJ (1996) The effect on human tumor necrosis factor alpha and interleukin 1 beta production of diets enriched in n-3 fatty acids from vegetable oil or fish oil. Am J Clin Nutr 63:116–122PubMedGoogle Scholar
  85. 85.
    Zhao Y, Joshi-Barve S, Barve S, Chen LH (2004) Eicosapentaenoic acid prevents LPS-induced TNF-α expression by preventing NF-κB activation. J Am Coll Nutr 23:71–78PubMedCrossRefGoogle Scholar
  86. 86.
    Kelley DS, Taylor PC, Nelson GJ, Schmidt P, Ferretti A, Erickson K, Yu R, Chandra R, Mackey BE (1999) Docosahexaenoic acid ingestion inhibits natural killer cell activity and production of inflammatory mediators in young healthy men. Lipids 34:317–324PubMedCrossRefGoogle Scholar
  87. 87.
    Vedin I, Cederholm T, Freund Levi Y, Basun H, Garlind A, Faxén Irving G, Jönhagen ME, Vessby B, Wahlund L-O, Palmblad J (2008) Effects of docosahexaenoic acid–rich n − 3 fatty acid supplementation on cytokine release from blood mononuclear leukocytes: the OmegAD study. Am J Clin Nutr 87:1616–1622PubMedGoogle Scholar
  88. 88.
    Miles EA, Calder PC (2012) Influence of marine n-3 polyunsaturated fatty acids on immune function and a systematic review of their effects on clinical outcomes in rheumatoid arthritis. Br J Nutr 107:S171–S184PubMedCrossRefGoogle Scholar
  89. 89.
    Schmitz G, Ecker J (2008) The opposing effects of n − 3 and n − 6 fatty acids. Prog Lipid Res 47:147–155PubMedCrossRefGoogle Scholar
  90. 90.
    Sculley DV (2014) Periodontal disease: modulation of the inflammatory cascade by dietary n-3 polyunsaturated fatty acids. J Periodontal Res 49:277–281PubMedCrossRefGoogle Scholar
  91. 91.
    Lo C-J, Chiu KC, Fu M, Lo R, Helton S (1999) Fish oil decreases macrophage tumor necrosis factor gene transcription by altering the NFκB activity. J Surg Res 82:216–221PubMedCrossRefGoogle Scholar
  92. 92.
    Novak TE, Babcock TA, Jho DH, Helton WS, Espat NJ (2003) NF-κB inhibition by ω-3 fatty acids modulates LPS-stimulated macrophage TNF-α-transcription. Am J Physiol Lung Cell Mol Physiol 284:L84–L89PubMedCrossRefGoogle Scholar
  93. 93.
    Sanlioglu S, Williams CM, Samavati L, Butler NS, Wang G, McCray PB, Ritchie TC, Hunninghake GW, Zandi E, Engelhardt JF (2001) Lipopolysaccharide induces Rac1-dependent reactive oxygen species formation and coordinates tumor necrosis factor-α secretion through IKK regulation of NF-κB. J Biol Chem 276:30188–30198PubMedCrossRefGoogle Scholar
  94. 94.
    Berger J, Moller DE (2002) The mechanisms of action of PPARs. Annu Rev Med 53:409–435PubMedCrossRefGoogle Scholar
  95. 95.
    Oh DY, Talukdar S, Bae EJ, Imamura T, Morinaga H, Fan W, Li P, Lu WJ, Watkins SM, Olefsky JM (2010) GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell 142:687–698PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Shaikh SR, Jolly CA, Chapkin RS (2012) n − 3 Polyunsaturated fatty acids exert immunomodulatory effects on lymphocytes by targeting plasma membrane molecular organization. Mol Asp Med 33:46–54CrossRefGoogle Scholar
  97. 97.
    Zeyda M, Stulnig TM (2006) Lipid Rafts & Co.: An integrated model of membrane organization in T cell activation. Prog Lipid Res 45:187–202PubMedCrossRefGoogle Scholar
  98. 98.
    Stulnig TM, Berger M, Sigmund T, Raederstorff D, Stockinger H, Waldhäusl W (1998) Polyunsaturated fatty acids inhibit t cell signal transduction by modification of detergent-insoluble membrane domains. J Cell Biol 143:637–644PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Fan Y-Y, Ly LH, Barhoumi R, McMurray DN, Chapkin RS (2004) Dietary docosahexaenoic acid suppresses T cell protein kinase Cθ lipid raft recruitment and IL-2 production. J Immunol 173:6151–6160PubMedCrossRefGoogle Scholar
  100. 100.
    Levy BD, Clish C, Schmidt B, Gronert K, Serhan CN (2001) Lipid mediator class switching during acute inflammation: signals in resolution. Nat Immun 2:612–619CrossRefGoogle Scholar
  101. 101.
    Serhan CN (2005) Lipoxins and aspirin-triggered 15-epi-lipoxins are the first lipid mediators of endogenous anti-inflammation and resolution. Prostaglandins Leukot Essent Fat Acids 73:141–162CrossRefGoogle Scholar
  102. 102.
    Van Dyke TE (2011) Proresolving lipid mediators: potential for prevention and treatment of periodontitis. J Clin Periodontol 38:119–125PubMedCrossRefGoogle Scholar
  103. 103.
    Das UN (2011) Lipoxins as biomarkers of lupus and other inflammatory conditions. Lipids Health Dis 10:76PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Serhan CN, Clish CB, Brannon J, Colgan SP, Chiang N, Gronert K (2000) Novel functional sets of lipid-derived mediators with antiinflammatory actions generated from omega-3 fatty acids via cyclooxygenase 2‚ÄìNonsteroidal antiinflammatory drugs and transcellular processing. J Exp Med 192:1197–1204PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Serhan CN, Chiang N (2008) Endogenous pro-resolving and anti-inflammatory lipid mediators: a new pharmacologic genus. Br J Pharmacol 153(Suppl 1):S200–S215PubMedPubMedCentralGoogle Scholar
  106. 106.
    Maddox JF, Colgan SP, Clish CB, Petasis NA, Fokin VV, Serhan CN (1998) Lipoxin B4 regulates human monocyte/neutrophil adherence and motility: design of stable lipoxin B4 analogs with increased biologic activity. FASEB J 12:487–494PubMedGoogle Scholar
  107. 107.
    Bannenberg G, Moussignac RL, Gronert K, Devchand PR, Schmidt BA, Guilford WJ, Bauman JG, Subramanyam B, Perez HD, Parkinson JF, Serhan CN (2004) Lipoxins and novel 15-epi-lipoxin analogs display potent anti-inflammatory actions after oral administration. Br J Pharmacol 143:43–52PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Pouliot M, Clish CB, Petasis NA, Van Dyke TE, Serhan CN (2000) Lipoxin A[4] analogues inhibit leukocyte recruitment to Porphyromonas gingivalis: a role for cyclooxygenase-2 and lipoxins in periodontal disease. Biochemistry 39:4761–4768PubMedCrossRefGoogle Scholar
  109. 109.
    Serhan CN, Hong S, Gronert K, Colgan SP, Devchand PR, Mirick G, Moussignac RL (2002) Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals. J Exp Med 196:1025–1037PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Serhan CN, Chiang N (2004) Novel endogenous small molecules as the checkpoint controllers in inflammation and resolution: entree for resoleomics. Rheum Dis Clin N Am 30:69–95CrossRefGoogle Scholar
  111. 111.
    Schwab JM, Chiang N, Arita M, Serhan CN (2007) Resolvin E1 and protectin D1 activate inflammation-resolution programmes. Nature 447:869–874PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Hong S, Gronert K, Devchand PR, Moussignac RL, Serhan CN (2003) Novel docosatrienes and 17S-resolvins generated from docosahexaenoic acid in murine brain, human blood, and glial cells. Autacoids in anti-inflammation. J Biol Chem 278:14677–14687PubMedCrossRefGoogle Scholar
  113. 113.
    Keinan D, Leigh NJ, Nelson JW, De Oleo L, Baker OJ (2013) Understanding resolvin signaling pathways to improve oral health. Int J Mol Sci 14:5501–5518PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Isobe Y, Arita M, Matsueda S, Iwamoto R, Fujihara T, Nakanishi H, Taguchi R, Masuda K, Sasaki K, Urabe D, Inoue M, Arai H (2012) Identification and structure determination of novel anti-inflammatory mediator resolvin E3, 17,18-dihydroxyeicosapentaenoic acid. J Biol Chem 287:10525–10534PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    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 102:7671–7676PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Hasturk H, Kantarci A, Goguet-Surmenian E, Blackwood A, Andry C, Serhan CN, Van Dyke T (2007) Resolvin E1 regulates inflamation at the cellular and tissue level and restores tissue homeostasis in vivo. J Immunol 179:7021–7029PubMedCrossRefGoogle Scholar
  117. 117.
    Ho KJ, Spite M, Owens CD, Lancero H, Kroemer AH, Pande R, Creager MA, Serhan CN, Conte MS (2010) Aspirin-triggered lipoxin and resolvin E1 modulate vascular smooth muscle phenotype and correlate with peripheral atherosclerosis. Am J Pathol 177:2116–2123PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Makriyannis A, Nikas SP (2011) Aspirin-triggered metabolites of EFAs. Chem Biol 18:1208–1209PubMedCrossRefGoogle Scholar
  119. 119.
    Oh SF, Pillai PS, Recchiuti A, Yang R, Serhan CN (2011) Pro-resolving actions and stereoselective biosynthesis of 18S E-series resolvins in human leukocytes and murine inflammation. J Clin Investig 121:569–581PubMedPubMedCentralCrossRefGoogle Scholar
  120. 120.
    Serhan CN (2009) Systems approach to inflammation resolution: identification of novel anti-inflammatory and pro-resolving mediators. J Thromb Haemost 7(Suppl 1):44–48PubMedCrossRefGoogle Scholar
  121. 121.
    Herrera BS, Ohira T, Gao L, Omori K, Yang R, Zhu M, Muscara M, Serhan CN, Van Dyke T, Gyurko R (2008) An endogenous regulator of inflammation, resolvin E1, modulates osteoclast differentiation and bone resorption. Br J Pharmacol 155:1214–1223PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Serhan CN, Gotlinger K, Hong S, Lu Y, Siegelman J, Baer T, Yang R, Colgan SP, Petasis NA (2006) Anti-inflammatory actions of neuroprotectin D1/protectin D1 and its natural stereoisomers: assignments of dihydroxy-containing docosatrienes. J Immunol 176:1848–1859PubMedCrossRefGoogle Scholar
  123. 123.
    Anderson P, Delgado M (2008) Endogenous anti-inflammatory neuropeptides and pro-resolving lipid mediators: a new therapeutic approach for immune disorders. J Cell Mol Med 12:1830–1847PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Bento AF, Claudino RF, Dutra RC, Marcon R, Calixto JB (2011) Omega-3 fatty acid-derived mediators 17[R]-hydroxy docosahexaenoic acid, aspirin-triggered resolvin D1 and resolvin D2 prevent experimental colitis in mice. J Immunol 187:1957–1969PubMedCrossRefGoogle Scholar
  125. 125.
    Shinohara M, Mirakaj V, Serhan CN (2012) Functional metabolomics reveals novel active products in the DHA metabolome. Front Immunol 3:81PubMedPubMedCentralCrossRefGoogle Scholar
  126. 126.
    Deng B, Wang CW, Arnardottir HH, Li Y, Cheng CY, Dalli J, Serhan CN (2014) Maresin biosynthesis and identification of maresin 2, a new anti-inflammatory and pro-resolving mediator from human macrophages. PLoS One 9, e102362PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Norling LV, Serhan CN (2010) Profiling in resolving inflammatory exudates identifies novel anti-inflammatory and pro-resolving mediators and signals for termination. J Intern Med 268:15–24PubMedGoogle Scholar
  128. 128.
    Freire MO, Van Dyke TE (2013) Natural resolution of inflammation. Periodontol 2000 63:149–164PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    Burr ML, Gilbert JF, Holliday RM, Elwood PC, Fehily AM, Rogers S, Sweetnam PM, Deadman NM (1989) Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial [DART]. Lancet 334:757–761CrossRefGoogle Scholar
  130. 130.
    Singh R, Niaz M, Sharma J, Kumar R, Rastogi V, Moshiri M (1997) Randomized, double-blind, placebo-controlled trial of fish oil and mustard oil in patients with suspected acute myocardial infarction: the Indian experiment of infarct survival-4. Cardiovasc Drugs Ther 11:485–491PubMedCrossRefGoogle Scholar
  131. 131.
    Bucher HC, Hengstler P, Schindler C, Meier G (2002) N-3 polyunsaturated fatty acids in coronary heart disease: a meta-analysis of randomized controlled trials. Am J Med 112:298–304PubMedCrossRefGoogle Scholar
  132. 132.
    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. J Am Med Assoc 308:1024–1033CrossRefGoogle Scholar
  133. 133.
    Hansson GK, Libby P, Schönbeck U, Yan ZQ (2002) Innate and adaptive immunity in the pathogenesis of atherosclerosis. Circ Res 91:281–291PubMedCrossRefGoogle Scholar
  134. 134.
    Meydani SN, Endres S, Woods MM, Goldin BR, Soo C, Morrill-Labrode A, Dinarello CA, Gorbach SL (1991) Oral [n-3] fatty acid supplementation suppresses cytokine production and lymphocyte proliferation: comparison between young and older women. J Nutr 121:547–555PubMedGoogle Scholar
  135. 135.
    Alam SQ, Bergens BM, Alam BS (1991) Arachidonic acid, prostaglandin E2 and leukotriene C4 levels in gingiva and submandibular salivary glands of rats fed diets containing n − 3 fatty acids. Lipids 26:895–900PubMedCrossRefGoogle Scholar
  136. 136.
    Campan P, Planchand P-O, Duran D (1997) Pilot study on n-3 polyunsaturated fatty acids in the treatment of human experimental gingivitis. J Clin Periodontol 24:907–913PubMedCrossRefGoogle Scholar
  137. 137.
    Boyle WJ, Simonet WS, Lacey DL (2003) Osteoclast differentiation and activation. Nature 423:337–342PubMedCrossRefGoogle Scholar
  138. 138.
    Redlich K, Smolen JS (2012) Inflammatory bone loss: pathogenesis and therapeutic intervention. Nat Rev Drug Discov 11:234–250PubMedCrossRefGoogle Scholar
  139. 139.
    Nakashima T, Kobayashi Y, Yamasaki S, Kawakami A, Eguchi K, Sasaki H, Sakai H (2000) Protein expression and functional difference of membrane-bound and soluble receptor activator of NF-kappaB ligand: modulation of the expression by osteotropic factors and cytokines. Biochem Biophys Res Commun 275:768–775PubMedCrossRefGoogle Scholar
  140. 140.
    Mizuno A, Kanno T, Hoshi M, Shibata O, Yano K, Fujise N, Kinosaki M, Yamaguchi K, Tsuda E, Murakami A, Yasuda H, Higashio K (2002) Transgenic mice overexpressing soluble osteoclast differentiation factor [sODF] exhibit severe osteoporosis. J Bone Miner Metab 20:337–344PubMedCrossRefGoogle Scholar
  141. 141.
    Hofbauer LC, Heufelder AE (2001) Role of receptor activator of nuclear factor-kappaB ligand and osteoprotegerin in bone cell biology. J Mol Med 79:243–253PubMedCrossRefGoogle Scholar
  142. 142.
    Caetano-Lopes J, Canhao H, Fonseca JE (2009) Osteoimmunology--the hidden immune regulation of bone. Autoimmun Rev 8:250–255PubMedCrossRefGoogle Scholar
  143. 143.
    Rahman MM, Bhattacharya A, Fernandes G (2008) Docosahexaenoic acid is more potent inhibitor of osteoclast differentiation in RAW 264.7 cells than eicosapentaenoic acid. J Cell Physiol 214:201–209PubMedCrossRefGoogle Scholar
  144. 144.
    Sun D, Krishnan A, Zaman K, Lawrence R, Bhattacharya A, Fernandes G (2003) Dietary n-3 fatty acids decrease osteoclastogenesis and loss of bone mass in ovariectomized mice. J Bone Miner Res 18:1206–1216PubMedCrossRefGoogle Scholar
  145. 145.
    Kesavalu L, Bakthavatchalu V, Rahman MM, Su J, Raghu B, Dawson D, Fernandes G, Ebersole JL (2007) Omega-3 fatty acid regulates inflammatory cytokine/mediator messenger RNA expression in Porphyromonas gingivalis-induced experimental periodontal disease. Oral Microbiol Immunol 22:232–239PubMedCrossRefGoogle Scholar
  146. 146.
    Bendyk A, Marino V, Zilm PS, Howe P, Bartold PM (2009) Effect of dietary omega-3 polyunsaturated fatty acids on experimental periodontitis in the mouse. J Periodontal Res 44:211–216PubMedCrossRefGoogle Scholar
  147. 147.
    Martin-Bautista E, Munoz-Torres M, Fonolla J, Quesada M, Poyatos A, Lopez-Huertas E (2010) Improvement of bone formation biomarkers after 1-year consumption with milk fortified with eicosapentaenoic acid, docosahexaenoic acid, oleic acid, and selected vitamins. Nutr Res 30:320–326PubMedCrossRefGoogle Scholar
  148. 148.
    Kruger MC, Coetzer H, de Winter R, Gericke G, van Papendorp DH (1998) Calcium, gamma-linolenic acid and eicosapentaenoic acid supplementation in senile osteoporosis. Aging 10:385–394PubMedGoogle Scholar
  149. 149.
    Huang CB, Ebersole JL (2010) A novel bioactivity of omega-3 polyunsaturated fatty acids and their ester derivatives. Mol Oral Microbiol 25:75–80PubMedCrossRefGoogle Scholar
  150. 150.
    Higgins J, Green S (2011) Cochrane Handbook for Systematic Reviews of Interventions 5.2.1 [updated March 2011]. The Cochrane CollaborationGoogle Scholar
  151. 151.
    Vardar S, Buduneli E, Türkoǧlu O, Berdeli AH, Baylas H, Başkesen A, Atilla G (2004) Therapeutic versus prophylactic plus therapeutic administration of omega-3 fatty acid on endotoxin-induced periodontitis in rats. J Periodontol 75:1640–1646PubMedCrossRefGoogle Scholar
  152. 152.
    Vardar-Şengül S, Buduneli N, Buduneli E, Kardeşler L, Baylas H, Atilla G, Lappin D, Kinane DF (2006) Dietary supplementation of omega-3 fatty acid and circulating levels of interleukin-1β, osteocalcin, and C-reactive protein in rats. J Periodontol 77:814–820PubMedCrossRefGoogle Scholar
  153. 153.
    Hasturk H, Kantarci A, Ohira T, Arita M, Ebrahimi N, Chiang N, Petasis NA, Levy BD, Serhan CN, Van Dyke TE (2006) RvE1 protects from local inflammation and osteoclast-mediated bone destruction in periodontitis. FASEB J 20:401–403PubMedGoogle Scholar
  154. 154.
    Bartold PM, Van Dyke TE (2013) Periodontitis: a host-mediated disruption of microbial homeostasis. Unlearning learned concepts. Periodontol 2000 62:203–217PubMedCrossRefGoogle Scholar
  155. 155.
    Tanner AC, Kent RL Jr, Kanasi E, Lu SC, Paster BJ, Sonis ST (2007) Clinical characteristics and microbiota of progressing slight chronic periodontitis in adults. J Clin Periodontol 34:917–930PubMedCrossRefGoogle Scholar
  156. 156.
    Ramirez-Tortosa MC, Quiles JL, Battino M, Granados S, Morillo JM, Bompadre S, Newman HN, Bullon P (2010) Periodontitis is associated with altered plasma fatty acids and cardiovascular risk markers. Nutr Metab Cardiovasc Dis 20:133–139PubMedCrossRefGoogle Scholar
  157. 157.
    Figueredo CM, Martinez GL, Koury JC, Fischer RG, Gustafsson A (2013) Serum levels of long-chain polyunsaturated fatty acids in patients with periodontal disease. J Periodontol 84:675–682PubMedCrossRefGoogle Scholar
  158. 158.
    Requirand P, Gibert P, Tramini P, Cristol JP, Descomps B (2000) Serum fatty acid imbalance in bone loss: example with periodontal disease. Clin Nutr 19:271–276PubMedCrossRefGoogle Scholar
  159. 159.
    Naqvi AZ, Buettner C, Phillips RS, Davis RB, Mukamal KJ (2010) N-3 fatty acids and periodontitis in US adults. J Am Diet Assoc 110:1669–1675PubMedPubMedCentralCrossRefGoogle Scholar
  160. 160.
    Hamazaki K, Itomura M, Sawazaki S, Hamazaki T (2006) Fish oil reduces tooth loss mainly through its anti-inflammatory effects? Med Hypotheses 67:868–870PubMedCrossRefGoogle Scholar
  161. 161.
    Iwasaki M, Yoshihara A, Moynihan P, Watanabe R, Taylor GW, Miyazaki H (2010) Longitudinal relationship between dietary ω-3 fatty acids and periodontal disease. Nutrition 26:1105–1109PubMedCrossRefGoogle Scholar
  162. 162.
    Iwasaki M, Taylor GW, Moynihan P, Yoshihara A, Muramatsu K, Watanabe R, Miyazaki H (2011) Dietary ratio of n-6 to n-3 polyunsaturated fatty acids and periodontal disease in community-based older Japanese: a 3-year follow-up study. Prostaglandins Leukot Essent Fat Acids 85:107–112CrossRefGoogle Scholar
  163. 163.
    Rosenstein ED, Kushner LJ, Kramer N, Kazandjian G (2003) Pilot study of dietary fatty acid supplementation in the treatment of adult periodontitis. Prostaglandins Leukot Essent Fat Acids 68:213–218CrossRefGoogle Scholar
  164. 164.
    Parulkar M, Dawson DR, Kryscio R, Novak MJ, Ebersole JL, Boissonneault GB (2009) Lack of effect of omega-3 fatty acid [PUFA] dietary supplement on clinical measures of periodontitis in humans. FASEB J 23:LB454Google Scholar
  165. 165.
    El-Sharkawy H, Aboelsaad N, Eliwa M, Darweesh M, Alshahat M et al (2010) Adjunctive treatment of chronic periodontitis with daily dietary supplementation with omega-3 fatty acids and low-dose aspirin. J Periodontol 81:1635–1643PubMedCrossRefGoogle Scholar
  166. 166.
    Brown A, Pang E, Roberts D (1991) Persistent changes in the fatty acid composition of erythrocyte membranes after moderate intake of n-3 polyunsaturated fatty acids: study design implications. Am J Clin Nutr 54:668–673PubMedGoogle Scholar
  167. 167.
    Naqvi AZ, Hasturk H, Mu L, Phillips RS, Davis RB, Halem S, Campos H, Goodson JM, Van Dyke TE, Mukamal KJ (2014) Docosahexaenoic acid and periodontitis in adults: a randomized controlled trial. J Dent Res 93:767–773PubMedPubMedCentralCrossRefGoogle Scholar
  168. 168.
    Elkhouli AM (2011) The efficacy of host response modulation therapy (omega-3 plus low-dose aspirin) as an adjunctive treatment of chronic periodontitis (clinical and biochemical study). J Periodontal Res 46:261–268PubMedCrossRefGoogle Scholar
  169. 169.
    Kris-Etherton PM, Harris WS, Appel LJ, Committee N (2003) Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Arterioscler Thromb Vasc Biol 23:e20–e30PubMedCrossRefGoogle Scholar
  170. 170.
    Ågren JJ, Väisänen S, Hänninen O, Muller AD, Hornstra G (1997) Hemostatic factors and platelet aggregation after a fish-enriched diet or fish oil or docosahexaenoic acid supplementation. Prostaglandins Leukot Essent Fat Acids 57:419–421CrossRefGoogle Scholar
  171. 171.
    Bays HE (2007) Safety considerations with omega-3 fatty acid therapy. Am J Cardiol 99:S35–S43CrossRefGoogle Scholar
  172. 172.
    Buckley MS, Goff AD, Knapp WE (2004) Fish oil interaction with warfarin. Ann Pharmacother 38:50–53PubMedCrossRefGoogle Scholar
  173. 173.
    Holbrook AM, Pereira JA, Labiris R, McDonald H, Douketis JD, Crowther M, Wells PS (2005) Systematic overview of warfarin and its drug and food interactions. Arch Intern Med 165:1095–1106PubMedCrossRefGoogle Scholar
  174. 174.
    Harris WS (2007) Expert opinion: omega-3 fatty acids and bleeding—cause for concern? Am J Cardiol 99:S44–S46CrossRefGoogle Scholar
  175. 175.
    Domingo JL, Bocio A, Falcó G, Llobet JM (2007) Benefits and risks of fish consumption: part I. A quantitative analysis of the intake of omega-3 fatty acids and chemical contaminants. Toxicology 230:219–226PubMedCrossRefGoogle Scholar
  176. 176.
    Jacobs MN, Santillo D, Johnston PA, Wyatt CL, French MC (1998) Organochlorine residues in fish oil dietary supplements: comparison with industrial grade oils. Chemosphere 37:1709–1721PubMedCrossRefGoogle Scholar
  177. 177.
    Brasky TM, Darke AK, Song X, Tangen CM, Goodman PJ, Thompson IM, Meyskens FL, Goodman GE, Minasian LM, Parnes HL, Klein EA, Kristal AR (2013) Plasma phospholipid fatty acids and prostate cancer risk in the SELECT trial. J Natl Cancer Inst 105:1132–1141PubMedPubMedCentralCrossRefGoogle Scholar
  178. 178.
    Fay MP, Freedman LS, Clifford CK, Midthune DN (1997) Effect of different types and amounts of fat on the development of mammary tumors in rodents: a review. Cancer Res 57:3979–3988PubMedGoogle Scholar
  179. 179.
    Bartsch H, Nair J, Owen RW (1999) Dietary polyunsaturated fatty acids and cancers of the breast and colorectum: emerging evidence for their role as risk modifiers. Carcinogenesis 20:2209–2218PubMedCrossRefGoogle Scholar
  180. 180.
    Larsson SC, Kumlin M, Ingelman-Sundberg M, Wolk A (2004) Dietary long-chain n-3 fatty acids for the prevention of cancer: a review of potential mechanisms. Am J Clin Nutr 79:935–945PubMedGoogle Scholar
  181. 181.
    Norrish AE, Skeaff CM, Arribas GL, Sharpe SJ, Jackson RT (1999) Rostate cancer risk and consumption of fish oils: a dietary biomarker-based case–control study. Br J Cancer 81:1238–1242PubMedPubMedCentralCrossRefGoogle Scholar
  182. 182.
    Augustsson K, Michaud DS, Rimm EB, Leitzmann MF, Stampfer MJ, Willett WC, Giovannucci E (2003) A prospective study of intake of fish and marine fatty acids and prostate cancer. Cancer Epidemiol Biomarkers Prev 12:64–67PubMedGoogle Scholar
  183. 183.
    Leitzmann MF, Stampfer MJ, Michaud DS, Augustsson K, Colditz GC, Willett WC, Giovannucci EL (2004) Dietary intake of n − 3 and n − 6 fatty acids and the risk of prostate cancer. Am J Clin Nutr 80(204):216Google Scholar
  184. 184.
    Pham T-M, Fujino Y, Kubo T, Ide R, Tokui N, Mizoue T, Ogimoto I, Matsuda S, Yoshimura T (2009) Fish intake and the risk of fatal prostate cancer: findings from a cohort study in Japan. Public Health Nutr 12:609PubMedCrossRefGoogle Scholar
  185. 185.
    MacLean CH, Newberry SJ, Mojica WA, Khanna P, Issa AM, Suttorp MJ, Lim Y-W, Traina SB, Hilton L, Garland R (2006) Effects of omega-3 fatty acids on cancer risk. J Am Med Assoc 295:403–415CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • B. Chee
    • 1
  • B. Park
    • 1
  • T. Fitzsimmons
    • 1
  • A. M. Coates
    • 2
  • P. M. Bartold
    • 1
  1. 1.Department of Dentistry, Colgate Australian Clinical Dental Research Centre, Dental SchoolUniversity of AdelaideAdelaideAustralia
  2. 2.Alliance for Research in Exercise, Nutrition and Activity (ARENA), Sansom Institute for Health Research, Division of Health SciencesUniversity of South AustraliaAdelaideAustralia

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