Indian Journal of Dental Research

: 2020  |  Volume : 31  |  Issue : 2  |  Page : 229--235

Efficacy of omega 3 fatty acid as an adjunct in the management of chronic periodontitis: A randomized controlled trial

Shirish K Kujur, Varsha Goswami, Anand M Nikunj, Gangesh Singh, Shweta Bandhe, Himanta Ghritlahre 
 Department of Oral Pathology, Govt Dental College, Raipur, Chhattisgarh, India

Correspondence Address:
Dr. Shirish K Kujur
Govt Dental College, Raipur - 492 001, Chattisgarh


Background: Periodontitis is conventionally treated with both surgical and nonsurgical methods. Various adjuncts have been used previously with compromised efficacy. Recently omega-3(ώ-3) polyunsaturated fatty acids (PUFA) including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were shown to have therapeutic anti-inflammatory and protective actions in inflammatory diseases including periodontitis. The purpose of the present study was to evaluate and compare the clinical efficacy of ώ-3 fatty acids as an adjunct to scaling and root planing in the treatment of periodontitis. Methods: 110 Patients were selected for the study out of which 20 were excluded (12 not meeting the inclusion criteria and 8 refused to participate). 90 patients (48 in test and 42 in the control group) after randomisation through a coin toss method were enrolled in a single-blind randomised controlled trial conducted in the Periodontics department of a dental college. Full mouth subgingival scaling and root planing and ώ-3 fatty acid 500 mg (EPA/DHA 180/120 mg), BD daily for 1 month was given to the test group and subgingival scaling and root planing only was given to the control group. Clinical parameters like probing pocket depth, clinical attachment level, plaque index and gingival index were recorded at baseline, 1 and 3 months and were compared. Results: Statistical analyses demonstrated a significant reduction in probing pocket depth (t = 65.56, P = 0.000) and (t = 51.69, P = 0.000) at 1 and 3 months, respectively, in test group compared to baseline and control group. There was a significant gain in clinical attachment level (t = 63.29, P = 0.000) and (t = 31.03, P = 0.000) at 1 and 3 months, respectively, in test group compared to baseline and control group. The gingival index shows an appreciable reduction in both groups, and in test group, it is statistically significant at 3 months (t = 2.15, P = 0.03). There was no statistical significant reduction in plaque index at 3 months (t = 0, P = 0.997). Conclusion: The present study showed that adjunctive use of ώ-3 fatty acids proved to be beneficial over scaling and root planing alone in the treatment of chronic moderate periodontitis. The beneficial effects were in terms of significant improvements in clinical parameters, probing pocket depth, and clinical attachment level and gingival index. Dietary modulation is now emerging as an adjunct to periodontal therapy. Hence, omega-3 fatty acid may be used routinely in the management of chronic periodontitis.

How to cite this article:
Kujur SK, Goswami V, Nikunj AM, Singh G, Bandhe S, Ghritlahre H. Efficacy of omega 3 fatty acid as an adjunct in the management of chronic periodontitis: A randomized controlled trial.Indian J Dent Res 2020;31:229-235

How to cite this URL:
Kujur SK, Goswami V, Nikunj AM, Singh G, Bandhe S, Ghritlahre H. Efficacy of omega 3 fatty acid as an adjunct in the management of chronic periodontitis: A randomized controlled trial. Indian J Dent Res [serial online] 2020 [cited 2020 Jul 8 ];31:229-235
Available from:

Full Text


Periodontal tissue destruction occurs as a result of the interaction between dental plaque bacteria and the immune-inflammatory response induced by mediators like arachidonic acid metabolites, cytokines and enzymes. The levels of arachidonic acid metabolites are markedly increased in periodontal diseases, and it has been reported that they are involved in the pathogenesis of periodontal diseases. Various non-surgical methods have been tried in the treatment of periodontitis; antimicrobial therapies both local and systemic administration along with mechanical debridement are one of the mainstays in periodontal treatment strategies, which answered microbial aetiology of periodontal diseases. However, these treatment strategies failed to block (or) inhibit the host response-mediated tissue destruction due to continued bacterial challenge.[1]

Newly emerging chemical mediators derived from polyunsaturated fatty acids were identified to control the acute inflammatory response by activating local resolution.[2] Polyunsaturated fatty acids (PUFAs) are fatty acids with more than 1 carbon double bond, including omega-3 (ώ-3), omega-6 (ώ-6), and omega-9 (ώ-9) fatty acids. Fatty acids are obtained from marine sources, such as, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and vegetable sources, such as, linolenic acid (LA), which includes alpha-linolenic acid (ALA) and a related ώ-6 fatty acid, gamma-linolenic acid (GLA). All these fatty acids are shown to have anti-inflammatory properties.[3],[4] Increased consumption of long-chain ώ-3 PUFAs, such as eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3), results in increased proportions of those fatty acids in inflammatory cell phospholipids. The incorporation of EPA and DHA into human inflammatory cells occurs in a dose-response fashion and is partly at the expense of arachidonic acid.[5]

EPA can also act as a substrate for both cyclooxygenase (COX) and 5-lipooxygenase (5-LOX), giving rise to eicosanoids with a slightly different structure from those formed from arachidonic acid. Thus, fish oil supplementation of the human diet has been shown to result in increased production of leukotrieneB5 (LTB5), leukotrieneE5 (LTE5) and 5-hydroxyeicosapentaenoic acid by inflammatory cells, although generation of prostaglandin E3 (PGE3) has been more difficult to demonstrate. In addition to long-chain ώ-3 PUFAs modulating the generation of eicosanoids from arachidonic acid and to EPA acting as a substrate for the generation of alternative eicosanoids, recent studies have identified a novel group of mediators, termed E-series resolvins, formed from EPA by cyclooxygenase-2 (COX-2) that appear to exert anti-inflammatory actions.[6],[7],[8],[9] DHA-derived mediators termed D-series resolvins, docosatrienes and neuro-protectins, also produced by COX-2, have been identified and also appear to have anti-inflammatory actions.[10]

ώ-3 polyunsaturated fatty acids (ώ-3 PUFAs) including docosahexaenoic acid (DHA; C22:6 n-3) and eicosapentaenoic acid (EPA; C20:5 n-3) were shown to have therapeutic value and anti-inflammatory and protective actions in rheumatoid arthritis, atherosclerosis, cardiovascular disease and periodontitis.[11] The beneficial actions of ώ-3 PUFAs were attributed, at first, to a decrease in the production of classic inflammatory mediators such as arachidonic acid-derived eicosanoids (prostaglandin E2) and inflammatory cytokines.[12] However, seminal work by Serhan et al.[11],[13],[14],[15] and Hong et al.[10] demonstrated that ώ-3 PUFAs serve as substrates for enzymatic conversion to a novel series of lipid mediators that were named resolvins and protectins.

There is considerable interest in diet supplementation with ώ-3 PUFAs found in high concentrations in fish oil. Recent studies showed that EPA and DHA (essential ώ-3 PUFAs) undergo transcellular metabolism in human cells to produce a variety of powerful anti-inflammatory, pro-resolution, lipid mediators termed 18R-resolvins and 17R-docosatrienes, respectively.[16],[17],[18] These compounds impact several of the functional responses of isolated polymorphonuclear leukocytes (PMNs) in vitro and prevent inflammation in a variety of animal models.[19],[20] The presence of elevated levels of, or topical treatment with, these compounds protects the animals from tissue destruction in a variety of inflammatory-disease models.[17]Invitro work in humans demonstrated that these compounds block superoxide production, chemotaxis and transmigration of PMNs from people with diabetes in vitro upon stimulation with a wide variety of agonists.[18] ώ-3 is available in capsules form, from (fish oil) animal origin as well as plant origin with side effects usually rare. This present clinical trial is to compare and evaluate the efficacy of ώ– 3 fatty acids 500 mg BD daily as an adjunct to scaling and root planing in the treatment of chronic moderate periodontitis.

 Study Population

One hundred ten subjects were enrolled in the study, obtained prior approval for the study from the institutional Ethical Committee of the periodontics department of the college, between November 2014 and October 2015. The inclusion criteria for subjects included patients with the number of teeth present ≥20 teeth (not including third molars and teeth with orthodontic appliances, bridges, crowns, or implants), untreated chronic periodontitis, 30 to 70 years of age and without any systemic disease (assessed by a questionnaire). Moderate periodontitis was defined as CAL between 3 and 4 mm. Exclusion criteria for subjects included systemic illnesses (i.e., diabetes mellitus, cancer, human immunodeficiency syndrome, bone metabolic diseases, or disorders that compromise wound healing, radiation, or immunosuppressive therapy), smoking, pregnancy or lactation, systemic antibiotics taken within the previous 2 months, chronic use of NSAIDs and periodontal therapy within the previous year. After the study was explained, including the benefits, risks and alternative treatments, the patients signed an informed consent form indicating their agreement to participate in the study.

Twelve patients not fulfilling the inclusion criteria and 8 disagreed to participate were not included in the study. Ninety patients were randomised into test (48) and control (42) group by the coin toss method in a parallel, single-masked design [Figure 1]. The test group received SRP and ώ- 3 fatty acid 500 mg BD daily for 1 month, whereas the control group received standard non-surgical periodontal therapy (SRP) alone. Each capsule contained 500 mg (concentration of EPA 180/DHA120) supplied by Inlife Pharmaceuticals Pvt. Ltd. Hydearabad (license no T-2072/AYUR). At the baseline visit, all patients received a complete dental examination for initial documentation, including medical history, dental history, complete periodontal charting, panoramic radiographs and a comprehensive treatment plan.{Figure 1}

Clinical measurements included PD, CAL, plaque index (PI) and gingival index (GI). Initial therapy was performed on all patients and consisted of full-mouth SRP, by hand and with ultrasonic instrumentation as necessary, and oral hygiene instructions. Clinical assessments at baseline, 1 and 3 months were recorded and compared. 8 patients from the test and 6 patients from the control group were lost to follow-up [Consort statement [Figure 2]. Subjects came to the clinic every 4 weeks during the course of the experiment (12 weeks) to replenish their medication. Remaining medications were checked for compliance. At each evaluation visit (4, 8 and 12 weeks), safety, including oral soft and hard tissue examinations, and adverse-event evaluations were performed.{Figure 2}

Statistical analyses

The study was powered (90%) to detect a mean difference of 0.7 mm for PD assuming a 30% change in primary outcomes including PD and CAL within groups after treatment. Sample size calculated was n = 55 patients per group with chronic generalised moderate periodontitis from formula N = 2(Zα+Zβ) (s/d)2 according to the study by Sharkawy et al.[21] For the clinical measurements, average whole-mouth recordings were accepted as a unit. Baseline comparisons were made using the Student t-test. The level of significance was set at 0.05. The Independent t-test was used to determine significant changes among time points for the data presented in [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]. Data were analysed using computer software, statistical package for social sciences (SPSS 16.0).{Table 1}{Table 2}{Table 3}{Table 4}{Table 5}


Clinical outcomes

Ninety patients with an age range of 30 to 70 years (mean age: 45 years) were included in this study. The demographic distribution within the test and control groups revealed no statistical differences in the mean baseline values of PPD, CAL, PI and GI between groups regarding age, sex and occupation (P > 0.05). Patients were recalled after 1 month and 3 months and the same parameters were re-recorded [Table 1].

The mean baseline probing pocket depth (PPD) values for the test group was 3.77 ± 0.33 mm, whereas 3.73 ± 0.30 mm for the control group showing no statistical difference (P > 0.05). The change in mean PPD between the groups was analysed using Independent t-test. Statistical analysis showed that at 1 month, the mean change in PPD for the test group was 0.79 ± 0.03 mm and 0.17 ± 0.05 mm in control group, (t = 65.56, P = 0.000) which was significant statistically. On the 3rd month, the change in mean PPD was 1.0 ± 0.00 for the test group and. 50 ± 0.06 for the control group, (t = 51.69, P = 0.000) which was significant statistically. Hence, the above results showed that there was a statistically significant reduction in the probing pocket depth in the test group when compared to the control group in 1 month as well as 3 months and the same is depicted in [Graph 1] [Table 2].[INLINE:1]

The mean baseline clinical attachment level (CAL) value for the test group was 4.78 ± 0.25 mm and 4.62 ± 0.37 mm for the control group showing no statistical difference (P > 0.05). Statistical analysis showed that at 1 month, the change in CAL was 0.79 ± 0.03 for the test group and 0.17 ± 0.05 for the control group, (t = 63.29, P = 0.000) which was statistically significant. At 3 months, the change in CAL was 1.00 ± 0.00 for test group and 0.52 ± 0.10 for control group, (t = 31.03, P = 0.000) which was statistically significant. Hence, the above results showed that there was a statistically significant improvement in the clinical attachment level in test group when compared to the control group at 1 month and 3 months and the same is depicted in [Graph 2] [Table 3].[INLINE:2]

Difference between PI scores in the test group and control group was compared using Independent t-test. Statistical analysis showed that there was no statistically significant change in the plaque index during the study period between test group and control group between 1 month (0.21 ± 0.05) (t = 0.2, P = 0.841) and 3 months (0.40 ± 0.04) (t = 0, P = 0.997) and the same is depicted below in [Graph 3] [Table 4].[INLINE:3]

Difference between GI scores in the test group and control group was compared using Independent t-test. Statistical analysis showed that there was a reduction in gingival index from baseline to 1 month of 0.22 ± 0.2 in test group and 0.18 ± 0.2 in control group with (t = 0.72, P = 0.47) and 0.50 ± 0.3 mm in test group and 0.37 ± 0.2 mm in control group from baseline to 3 month with (t = 2.15, P = 0.03). The reduction in the gingival index in the test group compared to the control group was more and was statistically significant at the 3rd month and the same is depicted below in [Graph 4] [Table 5].[INLINE:4]


This article describes the successful use of ώ-3 fatty acid in humans as an adjunct to non-surgical treatment of periodontitis. In this parallel-design experiment, 90 subjects received (48 subjects received 500 mg ώ-3 PUFA along with SRP and 42 subjects received SRP only) periodontal treatment. In this clinical proof-of-principle study, 500 mg of ώ-3 fatty acid administered daily for 1 month significantly improved the outcome of standard SRP using PD and CAL and standard indices as outcome measures. American Health Association has recommended ώ-3 fatty acid consumption (about 1 g of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) per day.[22] In addition to evaluating the potential for HMT in periodontal treatment, the present study was performed in a public health clinical setting to evaluate the efficacy of ώ-3 fatty acid for providing an inexpensive, sustainable public health measure aimed at modifying the course of the periodontal disease. As with other inflammatory diseases and conditions, ώ-3 PUFA may provide a reasonable public health measure for the prevention of a modification of the course of inflammatory disease in susceptible populations.[21]

In the present clinical trial, there was no statistical difference between the groups for PD at baseline (P > 0.05). At 1 and 3 months, both groups showed significant improvement in PDs over baseline measurements. There was a statistically significant difference when the two groups were compared (P = 0.000). CAL reductions followed a similar pattern to PD measurements (P = 0.000). This is in accordance with study by Sharkawy et al.,[21] which shows a significant improvement of clinical measurement in patients (a reduction of 2.0 ± 0.9 mm PPD and 2.00 ± 1.0 mm gain in CAL). Another randomised clinical trial by Elkhouli et al.[23] also showed a significant improvement of clinical measurement (a reduction of 2.2 ± 0.7 mm in PPD and 2.5 ± 0.7 mm gain in CAL). Elwakeel and Hazaa[24] in their randomised clinical trial also demonstrated significant improvement in clinical parameters (a reduction of 2.9 ± 0.6 in PPD and 3.0 ± 1.7 mm gain in CAL).

The reason behind the reduction in PPD and gain in CAL can be attributed to the anti-inflammatory properties of ώ-3 fatty acid. They were shown to competitively inhibit the production of arachidonic acid metabolites via the cyclooxygenase and lipoxygenase pathways, thus reducing the synthesis of pro-inflammatory arachidonic acid metabolites accounting for the potent pro-resolving properties of ώ-3 PUFAs.[25] ώ-3 PUFAs reduce alveolar bone resorption through the reduction of osteoclastic activity and dampening of gingival inflammation through their anti-inflammatory properties.[26] Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the major ώ-3 PUFAs in fish oil, were found to alter cellular functions of polymorphonuclear leukocytes, COX modulate lymphocyte proliferation and enhance endogenous host antioxidant capacity. In addition, metabolism of ώ-3 PUFAs results in the production of the pro-resolving lipid mediators, resolvins and protectins with anti-inflammatory and immunoregulatory actions, through regulating the trafficking of inflammatory cells to the sites of inflammation and blocking proinflammatory cytokine production, thus enhancing clearance of inflammation within the lesion to promote tissue regeneration.[27],[28]

Throughout the study, plaque accumulation was kept at a minimum with no significant differences between the two groups. The PI reduction for the test and control groups was maintained at 3 months. There was no statistically significant difference between the two groups at different time intervals (P > 0.05) and this may be attributed to the same oral hygiene instruction given or because ώ-3 fatty acids may not be effective in plaque reduction.

GI scores tended to be lower in the test group; at 1 and 3 months, the mean was significantly reduced for both groups. The reduction in the gingival index in the test group compared to the control group was more and was statistically significant at 3rd month (P = 0.03). Findings related to reduction in gingival index with ώ-3 fatty acid are in agreement with the study carried on by Sharkawy et al.[21] indicating a significant reduction in gingival index (1.00 ± 0.4). The study by Elkhouli et al.[23] also showed (0.37 ± 0.5) significant reduction in gingival index. Another study by Elwakeel and Hazaa[24] (1.1 ± 0.5) reported that systemic administration of ώ-3 fatty acid results in a statistically significant reduction of gingival index.

Reduction in the gingival index can be attributed to the production of resolvins and docosatrienes. These compounds have potent anti-inflammatory and immune-regulatory effects by inhibiting superoxide production, chemotaxis and migration of PMNs and directly or indirectly reduce the production of pro-inflammatory enzymes and cytokines, thereby decreasing periodontal inflammation and bone loss.[20],[29] The significant reduction may be attributed to the beneficial effects of the ώ-3 fatty acid, which is a source of stable, pro-resolving lipid mediators. These bioactive lipid mediators were found to display potent pro-resolution and anti-fibrotic activities.[30]

Another possible mechanism by which the reduction of gingival inflammation is the level of monocyte chemoattractant protein-3 (MCP-3) chemokine c-c motif ligand (also known as CCL7) which can be simultaneously or selectively expressed in leukocyte subpopulations, mainly monocytes and lymphocytes. IL-1β, TNF-α, interferon-c and lipopolysaccharides induce overexpression of MCP-3 by endothelial cells, monocytes and fibroblasts, and thus, it is involved in the pathogenesis of many inflammatory diseases, including periodontitis.[31],[32] Dezerega et al.[33],[34] reported that gingival tissues from patients with chronic periodontitis expressed MCP-3, and they detected high levels of MCP-3 in gingival crevicular fluid from the same patients, particularly in progressive periodontal lesions. The same authors reported that the expression of MCP-3 mRNA and protein secretion can be induced in response to a number of proinflammatory stimuli, including IL-1β, TNF-α, lipopolysaccharides and interferon-α, all are proven to be directly related to disease progression in periodontitis.

From this clinical study, it is clear that systemic administration of ώ-3 fatty acid 500 mg BD daily for 1 month along with subgingival scaling is more efficacious than subgingival scaling and root planing alone in the management of chronic generalised moderate periodontitis.

Even though the importance of inflammation in the destruction of periodontal tissues has been known for over 50 years, the concept of immunomodulation to prevent periodontal destruction or enhance the beneficial effects of traditional therapy is only slowly gaining importance. The recognition that ώ-3 fatty acid has anti-inflammatory capabilities supports dietary supplementation as a safe clinical strategy. According to the result of the present clinical trial, systemic ώ-3 fatty acid as an adjunct to scaling and root planing is useful in the treatment of chronic generalised moderate periodontitis for achieving better clinical results. However, future studies in the form of multicentric trials should be undertaken to see the sustainability of the results. Effects of levels of biomarkers in monitoring the response to treatment in periodontitis patients should be evaluated to check the efficacy of ώ-3 fatty acid for a long time to validate the initial short term results reported here.


No external funding and conflicts of interest related to this study.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


1Vardar-Sengul S, Buduneli E, Turkoglu O, Buduneli N, Atilla G, Wahlgren J, et al. The effects of selective COX-2 inhibitor/celecoxib and omega-3 fatty acid on matrix metalloproteinases, TIMP-1, and laminin-5g2-chain immunolocalization in experimental periodontitis. J Periodontol 2008;79:1934-41.
2Farjana HN, Anand N, Chandrasekaran SC. Resolvins: A novel therapeutic approach in treating periodontal disease. Indian Journal of Multidiscip Dent 2015;5:10-4.
3Zhao G, Etherton TD, Martin KR, Gillies PJ, West SG, Kris-Etherton PM. Dietary alpha-linolenic acid inhibits proinflammatory cytokine production by peripheral blood mononuclear cells in hypercholesterolemic subjects. Am J Clin Nutr 2007;85:385-91.
4Eberhard J, Heilmann F, Açil Y, Albers HK, Jepsen S. Local application of n-3 or n-6 polyunsaturated fatty acids in the treatment of human experimental gingivitis. J Clin Periodontol 2002;29:364-9.
5Yaqoob P, Pala HS, Cortina-Borja M, Newsholme EA, Calder PC. Encapsulated fish oil enriched in α-tocopherol alters plasma phospholipid and mononuclear cell fatty acid compositions but not mononuclear cell functions. Eur J Clin Invest 2000;30:260-74.
6Lee TH, Hoover RL, Williams JD, Sperling RI, Ravalese J 3rd, Spur BW, et al. Effects of dietary enrichment with eicosapentaenoic acid and docosahexaenoic acid on in vitro neutrophil and monocyte leukotriene generation and neutrophil function. N Engl J Med 1985;312:1217-24.
7Sperling RI, Benincaso AI, Knoell CT, Larkin JK, Austen KF, Robinson DR. Dietary ώ-3 polyunsaturated fatty acids inhibit phosphoinositide formation and chemotaxis in neutrophils. J Clin Invest 1993;91:651-60.
8Von Schacky C, Kiefl R, Jendraschak E, Kaminski WE. N-3 fatty acids and cysteinyl leukotriene formation in humans in vitro, ex vivo and in vivo. J Lab Clin Med 1993;121:302-9.
9Serhan CN, Clish CB, Brannon J, Colgan SP, Gronert K, Chiang N. Anti-inflammatory lipid signals generated from dietary n_3 fatty acids via cyclooxygenase-2 and transcellular processing: A novel mechanism for NSAID and n_3 PUFA therapeutic actions. J Physiol Pharmacol 2000;4:643-54.
10Hong S, Gronert K, Devchand P, Moussignac RL, Serhan CN. Novel docosatrienes and 17S-resolvins generated from docosahexaenoic acid in murine brain, human blood and glial cells: Autocoids in anti-inflammation. J Biol Chem 2003;278:14677-87.
11Serhan CN, Chiang N, Van Dyke TE. Resolving inflammation: Dual anti-inflammatory and pro-resolution lipid mediators. Nature Rev Immunol 2008;8:349-61.
12Calder PC. n-3 polyunsaturated fatty acids, inflammation, and inflammatory disease. Am J Clin Nutr 2006;83(Suppl. 6):1505S-19S.
13Raffaelli L, Serini S, Piccioni E, Manicone PF, Berardi D, Perfetti G, et al. N-3 polyunsaturated fatty acid effect in periodontal disease: State of art and possible mechanisms involved. Int J Immunopathol Pharmacol 2008;21:261-6.
14Serhan CN, Hong S, Gronert K, Colgan SP, Devchand PR, Mirick G, et al. Resolvins: A family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counters proinflammation signals. J Exp Med 2002;196:1025-37.
15Serhan CN, Gotlinger K, Hong S, Arita M. Resolvins, docosatrienes, and neuroprotectins, novel omega- 3-derived mediators, and their aspirin-triggered endogenous epimers: An overview of their protective roles in catabasis. Prostaglandins Other Lipid Mediat 2004;73:155-72.
16Serhan CN. Novel chemical mediators in the resolution of inflammation: Resolvins and protectins. Anesthesiol Clin 2006;24:341-64.
17Campbell EL, Louis NA, Tomassetti SE, Canny GO, Arita M, Serhan CN, et al. Resolvin E1 promotes mucosal surface clearance of neutrophils: A new paradigm for inflammatory resolution. FASEB J 2007;21:3162-70.
18Chen LY, Lawson DL, Mehta JL. Reduction in human neutrophil superoxide anion generation by n-3 polyunsaturated fatty acids: Role of cyclooxygenase products and endothelium-derived relaxing factor. Thromb Res 1994;76:317-22.
19Kesavalu L, Bakthavatchalu V, Rahman MM, Su J, Raghu B, Dawson D, et al. Omega-3 fatty acid regulates inflammatory cytokine/mediator messenger RNA expression in Porphyromonas gingivalis-induced experimental periodontal disease. Oral Microbiol Immunol 2007;22:232-9.
20Vardar S, Buduneli E, Baylas H, Berdeli AH, Buduneli N, Atilla G. Individual and combined effects of a selective cyclooxygenase-2 inhibitor and omega-3 fatty acid on endotoxin-induced periodontitis in rats. J Periodontol 2005;76:99-106.
21El-Sharkawy H, Aboelsaad N, Elia M, Darweesh M, Alshahat M, Kantarci A, et al. Adjunctive treatment of chronic periodontitis with daily dietary supplementation with omega-3 fatty acids and low dose aspirin. J Periodontol 2010;81:1635-43.
22Bays HE. Safety considerations with omega-3 fatty acid therapy. Am J Cardiol 2007;99(Suppl):35C-43C.
23Elkhouli AM. The efficacy of host response modulation therapy (omega-3 plus low-dose aspirin) as an adjunctive treatment of chronic periodontitis (Clinical biochemical study). J Periodontal Res 2011;46:261-8.
24Elwakeel NM, Hazaa HH. Effect of omega 3 fatty acids plus low-dose aspirin on both clinical and biochemical profiles of patients with chronic periodontitis and type 2 diabetes: A randomized double blind placebo-controlled study. J Periodontal Res 2015;50:721-9.
25Van Dyke TE. The management of inflammation in periodontal disease. J Periodontol 2008;79:1601-8.
26Kesavalu L, Vasudevan B, Raghu B, Browning E, Dawson D, Novak JM, et al. Omega-3 Fatty acid effect on alveolar bone loss in rats. J Dent Res 2006;85:648-52.
27Serhan CN. Controlling the resolution of acute inflammation: A new genus of dual anti-inflammatory and pro-resolving mediators. J Periodontol 2008;79:1520-6.
28Schwab JM, Chiang N, Arita M, Serhan CN. Resolvin E1 and protectin D1 activate inflammation-resolution programmes. Nature 2007;447:869-74.
29Hasturk H, Kantarci A, Ohira T, Arita M, Ebrahimi N, Chiang N, et al. RvE1 protects from local inflammation and osteoclast-mediated bone destruction in periodontitis. FASEB J 2006;20:401-3.
30Serhan CN, Yacoubian S, Yang R. Anti-inflammatory and pro-resolving lipid mediators. Annu Rev Pathol Mech Dis 2008;3:279-312.
31Raman D, Sobolik-Delmaire T, Richmond A. Chemokines in health and disease. Exp Cell Res 2011;317:575-89.
32Preshaw PM, Taylor JJ. How has research into cytokine interactions and their role in driving immune responses impacted our understanding of periodontitis? J Clin Periodontol 2011;38:60-84.
33Dezerega A, Osorio C, Mardones J, Mundi V, Dutzan N, Franco M, et al. Monocyte chemotactic protein-3: Possible involvement in apical periodontitis chemotaxis. Int Endod J 2010;43:902-8.
34Dezerega A, Pozo P, Hernández M. Chemokine monocyte chemoattractant protein-3 in progressive periodontal lesions in patients with chronic periodontitis. J Periodontol 2010;81:267-76.