International Journal of Medical Science and Pharmaceutical Research

Polyunsaturated fatty acids (PUFAs) are essential fatty acids that have gained increasing attention because of their potential contributions to oral health and oral disease management. This narrative review provides an overview of PUFAs, discusses their biological roles in maintaining oral health, and summarizes current evidence regarding their therapeutic applications in oral diseases. Omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), exhibit anti-inflammatory, immunomodulatory, antioxidative, tissue-reparative, and microbiome-modulating properties that may support oral tissue homeostasis. Evidence suggests that these biological activities contribute to the reduction of periodontal inflammation, modulation of immune responses, attenuation of oxidative stress, promotion of tissue repair, and maintenance of oral microbial balance. Clinical studies have demonstrated the potential benefits of PUFAs in the management of recurrent aphthous stomatitis, oral mucositis, oral submucous fibrosis, periodontal diseases, oral cancer, and systemic conditions that affect oral health, such as Sjögren’s syndrome. In addition, omega-3 fatty acids have shown promise as adjunctive therapies capable of improving clinical outcomes when combined with conventional treatment approaches. Despite encouraging findings, challenges related to bioavailability, optimal dosage, long-term efficacy, and standardized treatment protocols remain. Overall, current evidence supports the potential role of PUFAs as dietary and therapeutic agents for promoting oral health and improving the management of oral diseases, although further high-quality clinical studies are required to strengthen the evidence base and facilitate clinical translation.

Polyunsaturated fatty acids, Omega-3, Omega-6, Oral health, Oral disease

1. Zheng P, Qiu X, Zhang L, Liu P, Peng Z, Huang Z. Comparative analysis of oral disorder burden in China and globally from 1990 to 2021 based on GBD data. Scientific Reports. 2025;15(1). doi: 10.1038/s41598-025-94899-x.
2. Baldi SL, Bridge G, Watt RG. Global Oral Health.  Sustainable Development Goals Series. 2023. p. 215-21.
3. Gamonal Aravena J. Challenges in oral health research with public health impact in Latin America. Revista de la Asociacion Odontologica Argentina. 2025;113(2). doi: 10.52979/raoa.1130801.1345.
4. Jin LJ, Lamster IB, Greenspan JS, Pitts NB, Scully C, Warnakulasuriya S. Global burden of oral diseases: emerging concepts, management and interplay with systemic health. Oral Diseases. 2016;22(7):609-19. doi: 10.1111/odi.12428.
5. Peres MA, Macpherson LMD, Weyant RJ, Daly B, Venturelli R, Mathur MR, et al. Oral diseases: a global public health challenge. The Lancet. 2019;394(10194):249-60. doi: 10.1016/S0140-6736(19)31146-8.
6. Alsabeeha NH, Al Shalabi MA, Al Shamsi NO, AlSamahi SA, Awad MA. Oral Health in the UAE: Current Status Within Global and Regional Perspectives. Healthcare in the United Arab Emirates. 2026. p. 657-77.
7. Kassebaum NJ, Smith AGC, Bernabé E, Fleming TD, Reynolds AE, Vos T, et al. Global, Regional, and National Prevalence, Incidence, and Disability-Adjusted Life Years for Oral Conditions for 195 Countries, 1990-2015: A Systematic Analysis for the Global Burden of Diseases, Injuries, and Risk Factors. Journal of Dental Research. 2017;96(4):380-7. doi: 10.1177/0022034517693566.
8. Wu J, Chen J, Lv C, Zhou L. Global, regional, and National levels and trends in burden of dental caries and periodontal disease from 1990 to 2035: result from the global burden of disease study 2021. BMC Oral Health. 2025;25(1). doi: 10.1186/s12903-025-06108-w.
9. Petersen PE, Bourgeois D, Ogawa H, Estupinan-Day S, Ndiaye C. The global burden of oral diseases and risks to oral health. Bulletin of the World Health Organization. 2005;83(9):661-9. 
10. Lu W, Du W, Duan X. Global, Regional, and National Burden of Oral Diseases in Older Adults Aged 65 Years And Over. International Dental Journal. 2026;76(1). doi: 10.1016/j.identj.2025.109297.
11. Shetty P, Shetty A, Kumari S. Micronutrients and oral health an opportunity to prevent oral diseases. Romanian Journal of Diabetes, Nutrition and Metabolic Diseases. 2020;26(3):311-6. doi: 10.2478/rjdnmd-2019-0032.
12. Sarode S, Sarode G, Premarajan A. Unbalanced Nutrition and Oral Health. Lifestyle in Oral Health and Disease: A Comprehensive Guide for Oral Healthcare Providers. 2025. p. 161-77.
13. Kaye J, Lee S, Chinn CH. The need for effective interprofessional collaboration between nutrition and dentistry. Frontiers in Public Health. 2025;13. doi: 10.3389/fpubh.2025.1534525.
14. Torres-Reyes P, Aguilera-Rojas SE, García LAR. Oral Health, Nutrition, and Quality of Life.  The Role of Nutrition in Integral Health and Quality of Life: Interdisciplinary Perspectives and Recent Research. 2024. p. 471-86.
15. Touger-Decker R, Mobley CC. Position of the American Dietetic Association: oral health and nutrition. Journal of the American Dietetic Association. 2007;107(8):1418-28. doi: 10.1016/j.jada.2007.06.003.
16. Huang CB, Ebersole JL. A novel bioactivity of omega-3 polyunsaturated fatty acids and their ester derivatives. Molecular Oral Microbiology. 2010;25(1):75-80. doi: 10.1111/j.2041-1014.2009.00553.x.
17. Azuma MM, Cardoso CDBM, da Silva CC, de Oliveira PHC, Jacinto RDC, Andrada AC, et al. The use of omega-3 fatty acids in the treatment of oral diseases. Oral Diseases. 2022;28(2):264-74. doi: 10.1111/odi.13667.
18. Lombardo YB, Chicco AG. Effects of dietary polyunsaturated n-3 fatty acids on dyslipidemia and insulin resistance in rodents and humans. A review. Journal of Nutritional Biochemistry. 2006;17(1):1-13. doi: 10.1016/j.jnutbio.2005.08.002.
19. Sampath H, Ntambi JM. Polyunsaturated fatty acid regulation of gene expression. Nutrition Reviews. 2004;62(9):333-9. doi: 10.1301/nr.2004.sept.333-339.
20. Mititelu M, Lupuliasa D, Neacșu SM, Olteanu G, Busnatu ȘS, Mihai A, et al. Polyunsaturated Fatty Acids and Human Health: A Key to Modern Nutritional Balance in Association with Polyphenolic Compounds from Food Sources. Foods. 2025;14(1). doi: 10.3390/foods14010046.
21. Jovanovic S, Dietrich D, Becker J, Kohlstedt M, Wittmann C. Microbial production of polyunsaturated fatty acids — high-value ingredients for aquafeed, superfoods, and pharmaceuticals. Current Opinion in Biotechnology. 2021;69:199-211. doi: 10.1016/j.copbio.2021.01.009.
22. Wysoczański T, Sokoła-Wysoczańska E, Pékala J, Lochyński S, Czyz K, Bodkowski R, et al. Omega-3 fatty acids and their role in central nervous system - A review. Current Medicinal Chemistry. 2016;23(8):816-31. doi: 10.2174/0929867323666160122114439.
23. von Elert E. Polyunsaturated Fatty Acids in Decomposing Leaf Litter. Methods to Study Litter Decomposition: A Practical Guide. 2020. p. 147-55.
24. Catalá A. Advancement in the knowledge of polyunsaturated fatty acids, from discovery to now.  Polyunsaturated Fatty Acids (PUFAs): Food Sources, Health Effects and Significance in Biochemistry. 2018. p. 129-60.
25. Shahidi F, Ambigaipalan P. Omega-3 Fatty Acids.  Encyclopedia of Food Chemistry. 2018. p. 465-71.
26. Panda C, Varadharaj S, Voruganti VS. PUFA, genotypes and risk for cardiovascular disease. Prostaglandins Leukotrienes and Essential Fatty Acids. 2022;176. doi: 10.1016/j.plefa.2021.102377.
27. Zamuz S, Pateiro M, Conte-Junior CA, Domínguez R, Nawaz A, Walayat N, et al. Fat and fatty acids.  Food Lipids: Sources, Health Implications, and Future Trends. 2022. p. 155-72.
28. Kroes R, Schaefer EJ, Squire RA, Williams GM. A review of the safety of DHA45-oil. Food and Chemical Toxicology. 2003;41(11):1433-46. doi: 10.1016/S0278-6915(03)00163-7.
29. Cherian G. Supplemental Flax and Impact on n3 and n6 Polyunsaturated Fatty Acids in Eggs.  Egg Innovations and Strategies for Improvements. 2017. p. 365-72.
30. Barreira L, Pereira H, Gangadhar KN, Custódio L, Varela J. Medicinal Effects of Microalgae-Derived Fatty Acids.  Handbook of Marine Microalgae: Biotechnology Advances. 2015. p. 209-31.
31. Abedi E, Sahari MA. Long-chain polyunsaturated fatty acid sources and evaluation of their nutritional and functional properties. Food Science and Nutrition. 2014;2(5):443-63. doi: 10.1002/fsn3.121.
32. Meyer BJ, Mann NJ, Lewis JL, Milligan GC, Sinclair AJ, Howe PRC. Dietary intakes and food sources of omega-6 and omega-3 polyunsaturated fatty acids. Lipids. 4 ed2003. p. 391-8.
33. Eickstaedt M, Beck KL, Conlon CA. New Zealand women have suboptimal intakes of long chain omega-3 polyunsaturated fatty acids during pregnancy - A cross sectional study. New Zealand Medical Journal. 2017;130(1462):37-45. 
34. Whelan J, Rust C. Innovative dietary sources of n-3 fatty acids. Annual review of nutrition. 2006;26:75-103. doi: 10.1146/annurev.nutr.25.050304.092605.
35. Rothenberg R. Omega-3 polyunsaturated fatty acids: What you need to know to save your (and your patient's) life.  Anti-Aging Therapeutics - 2005 Conference Year2005. p. 251-7.
36. Przerwa F, Kukowka A, Niezgoda J, Kotrych K, Uzar I. Use of polyunsaturated fatty acids in prevention and treatment of gastrointestinal diseases, obesity and cancer. Herba Polonica. 2022;68(2):76-85. doi: 10.2478/hepo-2022-0009.
37. Michalak A, Mosińska P, Fichna J. Polyunsaturated fatty acids and their derivatives: Therapeutic value for inflammatory, functional gastrointestinal disorders, and colorectal cancer. Frontiers in Pharmacology. 2016;7(DEC). doi: 10.3389/fphar.2016.00459.
38. Mironidou-Tzouveleki M, Filippiadou M, Imprialos K, Tzouvelekis I, Kalousis K. The role of polyunsaturated fatty acids in our diet. Epitheorese Klinikes Farmakologias kai Farmakokinetikes. 2014;32(1):17-24. 
39. La Guardia M, Giammanco S, Di Majo D, Tabacchi G, Tripoli E, Giammanco M. Omega 3 fatty acids: Biological activity and effects on human health. Panminerva Medica. 2005;47(4):245-57. 
40. Wiktorowska-Owczarek A, Berezińska M, Nowak JZ. PUFAs: Structures, metabolism and functions. Advances in Clinical and Experimental Medicine. 2015;24(6):931-41. doi: 10.17219/acem/31243.
41. Ghemiș L, Goriuc A, Jipu R, Foia LG, Luchian I. The Involvement of Resolvins in Pathological Mechanisms of Periodontal Disease Associated with Type 2 Diabetes: A Narrative Review. International Journal of Molecular Sciences. 2024;25(23). doi: 10.3390/ijms252312784.
42. Panezai J, van Dyke T. Polyunsaturated Fatty Acids and Their Immunomodulatory Actions in Periodontal Disease. Nutrients. 2023;15(4). doi: 10.3390/nu15040821.
43. Dragičević Tomičić D, Lešić N, Škrlec I, Steigmann L, Tseneva K, Čalušić Šarac M, et al. Effects of Vitamin D, Melatonin, and Omega-3 Fatty Acids on Periodontal Health: A Narrative Review. Dentistry Journal. 2025;13(4). doi: 10.3390/dj13040178.
44. González-Alva P, Solís-Suárez DL, Cifuentes-Mendiola SE, García-Hernández AL. A diet rich in omega-3 fatty acid improves periodontitis and tissue destruction by MMP2- and MMP9-linked inflammation in a murine model. Odontology. 2024;112(1):185-99. doi: 10.1007/s10266-023-00831-y.
45. Bendyk A, Marino V, Zilm PS, Howe P, Bartold PM. Effect of dietary omega-3 polyunsaturated fatty acids on experimental periodontitis in the mouse. Journal of Periodontal Research. 2009;44(2):211-6. doi: 10.1111/j.1600-0765.2008.01108.x.
46. Varela-López A, Giampieri F, Bullón P, Battino M, Quiles JL. Role of lipids in the onset, progression and treatment of periodontal disease. A systematic review of studies in humans. International Journal of Molecular Sciences. 2016;17(8). doi: 10.3390/ijms17081202.
47. Santonocito S, Polizzi A, Palazzo G, Indelicato F, Isola G. Dietary factors affecting the prevalence and impact of periodontal disease. Clinical, Cosmetic and Investigational Dentistry. 2021;13:283-92. doi: 10.2147/CCIDE.S288137.
48. Kumar A, Balkrishna A, Srivastava D, Rana M, Kukreti A, Kumari A, et al. Dietary Habits and Nature of the Oral Microbiome.  Oral Microbiome: Hygiene and Health. 2025. p. 55-67.
49. Parise-Vasco JM, Angamarca-Iguago J, Cagua-Ordoñez J, Cabrera B, Jima Gavilanes D, Horowitz R, et al. Traditional Foods, Oral Microbiome, and Systemic Health: Molecular Pathways Linking Nutrition and Oral Disease Prevention. International Journal of Molecular Sciences. 2026;27(5). doi: 10.3390/ijms27052412.
50. Nosratzehi T, Akar A. Efficacy of Omega-3 in Treatment of Recurrent Aphthous Stomatitis: A Randomised, Double-blind, Placebo-controlled Study. The Chinese journal of dental research : the official journal of the Scientific Section of the Chinese Stomatological Association (CSA). 2016;19(3):159-64. doi: 10.3290/j.cjdr.a36681.
51. Hadian Z, Moghadamnia AA, Kazemi S, Shirzad A. Effect of Omega-3 on Recurrent Aphthous Stomatitis and Improvement Quality of Life. International Journal of Dentistry. 2021;2021. doi: 10.1155/2021/6617575.
52. El Khouli AM, El-Gendy EA. Efficacy of omega-3 in treatment of recurrent aphthous stomatitis and improvement of quality of life: A randomized, double-blind, placebo-controlled study. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology. 2014;117(2):191-6. doi: 10.1016/j.oooo.2013.09.003.
53. Amani T, Dharman S. Effect of Omega-3 Polyunsaturated Fatty Acids in Management of Oral Mucosal Lesions: A Systematic Review with a Meta-Analysis Focused on Recurrent Aphthous Stomatitis. Journal of Indian Academy of Oral Medicine and Radiology. 2026;38(1):11-8. doi: 10.4103/jiaomr.jiaomr_103_25.
54. Lessa RC, Alves FA, Fortunati E, Lu J. Oral mucositis in cancer and potential use of omega-3 free fatty acids in its management: A review. Biomedicines. 2021;9(11). doi: 10.3390/biomedicines9111531.
55. Chandran KVA, Abhinethra MS, Deepak TA, Choudary AS, Upasana L. Effectiveness of Omega-3 fatty acids and spirulina as an adjuvant antioxidant to corticosteroid in the treatment of oral submucous fibrosis - A comparative study. Journal of Indian Academy of Oral Medicine and Radiology. 2022;34(2):150-5. doi: 10.4103/jiaomr.jiaomr_212_21.
56. Stańdo M, Lewkowicz N. Omega-3 Polyunsaturated Fatty Acids as an Adjunct to Non-Surgical Treatment of Periodontitis. European Journal of Lipid Science and Technology. 2019;121(4). doi: 10.1002/ejlt.201800345.
57. Stańdo M, Piatek P, Namiecinska M, Lewkowicz P, Lewkowicz N. Omega-3 polyunsaturated fatty acids epa and dha as an adjunct to non-surgical treatment of periodontitis: A randomized clinical trial. Nutrients. 2020;12(9):1-14. doi: 10.3390/nu12092614.
58. Yang Y, Ge M, Yu Z, Mao F, Xie C, Ge C. Systemic inflammation mediates the association between docosahexaenoic acid/docosapentaenoic acid ratio and the risk of periodontitis. Nutrition Research. 2025;143:44-55. doi: 10.1016/j.nutres.2025.09.008.
59. Iwasaki M, Taylor GW, Moynihan P, Yoshihara A, Muramatsu K, Watanabe R, et al. 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 Leukotrienes and Essential Fatty Acids. 2011;85(2):107-12. doi: 10.1016/j.plefa.2011.04.002.
60. Rosenstein ED, Kushner LJ, Kramer N, Kazandjian G. Pilot study of dietary fatty acid supplementation in the treatment of adult periodontitis. Prostaglandins Leukotrienes and Essential Fatty Acids. 2003;68(3):213-8. doi: 10.1016/S0952-3278(02)00272-7.
61. Keskiner I, Saygun I, Bal V, Serdar M, Kantarci A. Dietary supplementation with low-dose omega-3 fatty acids reduces salivary tumor necrosis factor-α levels in patients with chronic periodontitis: a randomized controlled clinical study. Journal of Periodontal Research. 2017;52(4):695-703. doi: 10.1111/jre.12434.
62. Hromcik F, Vokurka J, Kyr M, Izakovicova Holla L. Granulation Tissue Enhanced with Aspirin and Omega-3 PUFAs as a Local Adjunct to the Surgical Treatment of Periodontitis. European Journal of Lipid Science and Technology. 2021;123(2). doi: 10.1002/ejlt.202000259.
63. Azzi DV, Viafara JAS, Zangeronimo MG, Ribeiro Lima R, Marques LS, Pereira LJ. n-3 Ingestion may modulate the severity of periodontal disease? Systematic review. Critical Reviews in Food Science and Nutrition. 2018;58(11):1937-42. doi: 10.1080/10408398.2017.1278677.
64. Wang SH, Hung HC, Tsai CC, Huang MC, Ho KY, Wu YM, et al. Plasma polyunsaturated fatty acids and periodontal recovery in Taiwanese with periodontitis: A significant relationship. Archives of Oral Biology. 2014;59(8):800-7. doi: 10.1016/j.archoralbio.2014.04.009.
65. Chen Q, Wang J, Lin J, Chen L, Lin LS, Pan LZ, et al. Erythrocyte ω-3 polyunsaturated fatty acids are inversely associated with the risk of oral cancer: a case-control study. Nutrition and Diabetes. 2020;10(1). doi: 10.1038/s41387-020-00140-1.
66. 66. He B, Dong X, Lin Y, Lin J, Qiu Y, Lin L, et al. Associations of dietary and erythrocyte membrane fatty acids with overall survival in oral cancer: A prospective cohort study with mechanistic exploration. Clinical Nutrition. 2026;56. doi: 10.1016/j.clnu.2025.12.001.
67. Yum HW, Na HK, Surh YJ. Anti-inflammatory effects of docosahexaenoic acid: Implications for its cancer chemopreventive potential. Seminars in Cancer Biology. 2016;40_41:141-59. doi: 10.1016/j.semcancer.2016.08.004.
68. Yurko-Mauro K, Van Elswyk M, Teo L. A scoping review of interactions between omega-3 long-chain polyunsaturated fatty acids and genetic variation in relation to cancer risk. Nutrients. 2020;12(6). doi: 10.3390/nu12061647.
69. Carvalho TC, Cruz BCS, Viana MS, Martucci RB, Saraiva DCA, Reis PF. Effect of Nutritional Supplementation Enriched with Eicosapentaenoic Acid on Inflammatory Profile of Patients With Oral Cavity Cancer in Antineoplastic Pretreatment: A Controlled and Randomized Clinical Trial. Nutrition and Cancer. 2017;69(3):428-35. doi: 10.1080/01635581.2017.1274406.
70. Lu H, Zhang Z, Liu F. Comparison of EPA and DHA&EPA on body weight, BMI, and lean body mass in cancer patients: a network meta-analysis. Supportive Care in Cancer. 2025;33(12). doi: 10.1007/s00520-025-10044-4.
71. Hashemipour MA, Barzegari S, Kakoie S, Aghahi RH. Effects of Omega-3 Fatty Acids Against Chemotherapy-induced Mucositis: A Double-blind Randomized Clinical Trial. Wounds. 2017;29(12):360-6. 
72. Tang X, Li W, Zhong Q, Wan L. Effects of Omega­3 Fatty Acids on Oral Mucositis Induced by Anticancer Therapy: A Meta-Analysis. Nutrition and Cancer. 2025;77(6):600-9. doi: 10.1080/01635581.2025.2492135.
73. Morsy BM, El Domiaty S, Meheissen MAM, Heikal LA, Meheissen MA, Aly NM. Omega-3 nanoemulgel in prevention of radiation-induced oral mucositis and its associated effect on microbiome: a randomized clinical trial. BMC Oral Health. 2023;23(1). doi: 10.1186/s12903-023-03276-5.
74. Hashemipour MA, Ghasemi AR, Dogaheh MA, Torabi M. Effects of locally and systemically applied n-3 fatty acid on oral ulcer recovery process in rats. Wounds. 2012;24(9):258-66. 
75. Nave CBD, Pereira P, Silva ML. The Effect of Polyunsaturated Fatty Acid (PUFA) Supplementation on Clinical Manifestations and Inflammatory Parameters in Individuals with Sjögren’s Syndrome: A Literature Review of Randomized Controlled Clinical Trials. Nutrients. 2024;16(21). doi: 10.3390/nu16213786.
76. Azzolino D, Carnevale-Schianca M, Bottalico L, Colella M, Felicetti A, Perna S, et al. The Oral–Gut Microbiota Axis as a Mediator of Frailty and Sarcopenia. Nutrients. 2025;17(15). doi: 10.3390/nu17152408.
77. Zazula MF, Pozzan R, dos Reis GA, Maciel M, Horlem T, Banckes TN, et al. Advances in Oral Drug Delivery Systems for Natural Polyunsaturated Fatty Acids: Enhancing Bioavailability and Therapeutic Potential. Pharmaceutics. 2025;17(11). doi: 10.3390/pharmaceutics17111377.