|Year : 2022 | Volume
| Issue : 2 | Page : 150-155
Effectiveness of Omega-3 fatty acids and spirulina as an adjuvant antioxidant to corticosteroid in the treatment of oral submucous fibrosis – A comparative study
Kana Veettil Aiswarya Chandran1, Mariyappa Shantha Abhinethra2, Timmasandra Ashwathappa Deepak2, Amirneni Sailaja Choudary2, Lingaiah Upasana2
1 Private Practitioner, Mysuru, India
2 Deparment of Oral Medicine and Radiology, V S Dental College, Belangaluru, Karnataka, India
|Date of Submission||27-Jul-2021|
|Date of Decision||03-Jun-2022|
|Date of Acceptance||08-Jun-2022|
|Date of Web Publication||22-Jun-2022|
Kana Veettil Aiswarya Chandran
#173. F1 Shree Residency Apartments, Brindavan Extension 1st stage, Brindavan Extension, Mysore - 570020, Karnataka
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Introduction: Oral submucous fibrosis (OSMF) is a chronic insidious and a well-recognized potentially malignant disorder of the oral cavity. Due to its high morbidity and malignant transformation rate, relentless efforts have been made to improve effective management, despite not much improvement in the prognosis. Omega 3 polyunsaturated fatty acids have been reported to have anti-inflammatory properties. With its antioxidant, anti-inflammatory, and immunomodulating properties, Spirulina has shown promising results in the management of OSMF. This present study was conducted to compare the effectiveness of Omega-3 fatty acids and Spirulina in the management of OSMF. Aims and Objectives: To find out and compare the effectiveness of Omega-3 fatty acids and spirulina in the management of OSMF. Methods and Material: 40 OSMF patients with clinically diagnosed OSMF were selected and divided into two groups. Group A was given biweekly intralesional injections of 1.5 ml Dexamethasone in 4 mg/1 ml and Hyaluronidase 1500 IU mixed with Lignocaine 0.5 ml for six weeks and with omega-3 fatty acid capsules 1 gm three times daily for three months. Group B received similar intralesional injections but with spirulina 500 mg twice daily for three months. All the patients were followed up every month for 3 months and then after six months. Results: Both groups improved mouth opening, cheek flexibility, and VAS burning sensation except tongue protrusion (p < 0.05). When the efficacy was compared between two drugs, statistically insignificant results were found for mouth opening, tongue protrusion, cheek flexibility, and burning sensation. Conclusion: Omega 3 and Spirulina can be effective adjunctive treatment options in patients with OSMF to reduce subjective symptoms. Statistically, significant improvement was seen in both groups.
Keywords: Omega-3 polyunsaturated fatty acid, oral submucous fibrosis, spirulina
Key Messages: The present study is the first of its kind in which Omega 3 and Spirulina have been compared together in OSMF patients. Intergroup comparison showed that mouth opening, cheek flexibility, and VAS burning sensation were obtained except tongue protrusion
|How to cite this article:|
Chandran KV, 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. J Indian Acad Oral Med Radiol 2022;34:150-5
|How to cite this URL:|
Chandran KV, 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. J Indian Acad Oral Med Radiol [serial online] 2022 [cited 2022 Jul 1];34:150-5. Available from: https://www.jiaomr.in/text.asp?2022/34/2/150/347916
| Introduction|| |
Oral Submucous Fibrosis is a potentially malignant disorder. In 1966, Pindborg defined OSMF as “an insidious, chronic disease affecting any part of the oral cavity and sometimes pharynx. It is associated with juxta-epithelial inflammatory reaction followed by fibroelastic changes in the lamina propria layer, along with epithelial atrophy, which leads to rigidity of the oral mucosa proceeding to trismus and difficulty in mouth opening.” This condition is particularly associated with areca nut chewing, wagainin component of betel quid.
The prevalence of OSMF in India has ranged from 0.2 to 2.3% in males and 1.2 to 4.6% in females, with a broad age range from 11 to 60 years., A marked increase in incidence has been observed after the widespread marketing of commercial tobacco and areca nut products, generally known as Gutkha, sold in packets. Currently, it is estimated that the areca nut is consumed by 10–20% of the World's population in a widevariety of formulations.
The oral mucosa undergoes various changes like inflammation, ulcerations, pigmentation, loss of resilience and flexibility, to a significant blanched and fibrosis appearance leading to rigidity and progressive inability to open the mouth.
Omega 3 fatty acids are polyunsaturated essential fatty acids. Humans cannot synthesize them de novo and hence depend on the dietsourcesurce. Recent studies have investigated the beneficial effects of Omega 3 polyunsaturated fatty acids EPA (eicosapentaenoic acid) & DHA (Docosahexaenoic acid) on chronic inflammatory diseases. However, the role of omega 3 in OSMF has not been well established.
Spirulina, the blue-green algae, is a non-conventional, palatable, and filamentous cyanobacterium rich in β- carotene, proteins, vitamins, and other components with antioxidant properties and chemopreventive potential. Studies were done to evaluate the efficacy of Spirulina as adjuvant therapy in the management of OSMF and have shown promising results in the clinical improvements of OSMF.
Hence, the present study was conducted to evaluate the effectiveness of omega 3 fatty acids and spirulina and compare their effectiveness in OSMF.
| Material and Methods|| |
Ethical clearance number: KIMS/IEC/D15/2018
Date of approval: 10-11-2018
This study was conducted on 40 subjects clinically diagnosed with Oral Submucous Fibrosis reporting to the Department of Oral Medicine and Radiology V.S Dental College and Hospital Bangalore. Patients who were between the age of 18-60 years, with positive history of areca nut chewing or one of its commercial preparations, Patients who were clinically diagnosed with oral submucous fibrosis including the inability to open mouth, blanching, burning sensation on intake of hot and spicy food and presence of palpable fibrous bands were included in the study.
Patients. Suffering from any other systemic diseases like hypertension, diabetes, anemic stomatitis, scleroderma, radiation fibrosis, and cardiovascular system disorders and patients with any other mucosal disease or any other skin lesions were excluded from the study.
After establishing a diagnosis, each patient was educated about their condition and its precancerous potential and instructed to stop the habit in all forms. The patients were informed about all the procedures performed during the study. Informed consent was elaborated history was taken, including the habit history, form, the type used, frequency, and duration in years. The subjects were classified based on Haider et al. Functional classification and clinical classification in this study. Most subjects belonged to functional stage 1 and clinical stage 2 categories [Table 7].
Forty patients with clinically confirmed OSMF were divided equally into two groups by a simple randomization method. Group A was given Omega-3 fatty acids; Group B was given Spirulina. Group A was given biweekly intralesional injections of 1.5 ml Dexamethasone in 4 mg/ml concentration and Hyaluronidase 1500 IU mixed with 0.5 ml Lignocaine for six weeks and with omega-3 fatty acid capsules 1 gm three times daily for three months. Group B was also given similar intralesional injections and spirulina 500 mg twice daily for three months [Table 8]. Patients of both the groups were followed up every month for three months and then after six months. Patients were evaluated for mouth opening based on inter-incisal distance, tongue protrusion, cheek flexibility, and burning sensation.
Mouth opening was measured as the distance between the incisal edges of upper and lower central incisors when maximally extended with a scale and divider. Normal values were 35-45 mm in males and 30-42 mm in females. Tongue protrusion was measured as the distance from the mesio-incisal edge of the central incisor to the tip of the protruded tongue. Normal values were taken as 5-6 cms in males and 4.5-5.5 cms in females. Cheek flexibility is recorded based on the distance between specified points on the cheek skin. V1 and V2, in normal position and with cheeks blown out and Cheek Flexibility = V1-V2, where V1 has marked one-third the distance from the angle of the mouth on a line joining the tragus of the ear and angle of the mouth. Then subjects were asked to blow their cheeks fully, and V2 was assured. The mean value for males and females was taken as 1.2 cm and 1.08 cm, respectively. The burning sensation was determined by a 0-10 Visual Analogue Scale (VAS).
Data were analyzed using the statistical package SPSS 22.0 (SPSS Inc., Chicago, IL), and the level of significance will be set at P < 0.05. Descriptive statistics were performed to assess the mean and standard deviation of the respective groups. The normality of the data was assessed using the Shapiro–Wilkinson test. Inferential statistics to determine the difference between and within the groups using Student t test and one-way ANOVA and Tukey's post hoc test. Chi-square test was used to test the proportion.
| Results|| |
Age and gender distribution between Omega 3 and Spirulina group [Table 1] and [Table 2]
A total of 40 patients were included in the study. The mean age of the study participants in the omega 3 group was 37.6 ± 9.5, and in the spirulina, the group was 38.3 ± 6.8. Out of 20 patients in groups, 85% were males and 15% were females in the omega 3 group, 75% were males, and 25% were females in the spirulina group.
The comparison of mean difference in mouth opening between omega 3 group and spirulina group at different time intervals using post hoc test.
The mean comparison by ANOVA and Bonferroni's correction showed a statistically significant difference between the baseline and the subsequent visit (p < 0.05).
The mean difference between the 1st visit and 3rd-month follow-up and the 1st visit 6th-month follow-up was statistically significant (p < 0.05).
Intergroup comparison of mouth opening [Table 3]
Comparison of mean mouth opening (in cm) between Omega 3 and Spirulina group at different time intervals using independent Student t-test.
The mean mouth opening between-group comparison using the Independent t-test shows no significant difference exists between Omega 3 and Spirulina groups at various time intervals (p > 0.05).
The comparison of mean difference in tongue protrusion (in cm) between different time intervals in omega 3 group and spirulina group using post hoc test (Tukey HSD test).
The multiple mean comparisons by ANOVA and Bonferroni's correction showed no statistically significant difference between the baseline and the subsequent visit (p > 0.05).
The mean difference between the groups showed no statistical significance (p > 0.05).
Intergroup comparison of tongue protrusion [Table 4]
Comparison of mean tongue protrusion (in cm) between Omega 3 and Spirulina group at different time intervals using independent Student t-test
The mean measurement of tongue protrusion between-group comparison using an independent t-test shows no significant difference exists between Omega 3 and Spirulina groups at various time intervals (p > 0.05).
The comparison of the comparison of mean difference in cheek flexibility between omega 3 group and spirulina group at different time intervals using post hoc test mean difference in cheek flexibility (in cm) between different time intervals in Omega 3 group and Spirulina group using post hoc test (Tukey HSD test)
The multiple mean comparisons by ANOVA and Bonferroni's correction showed a statistically significant difference between the baseline and the subsequent visit (p < 0.05).
The mean difference between the 1st visit and 3rd month, 1st visit, and 6th month follow-up showed statistically significant (p < 0.05).
Intergroup comparison of cheek flexibility [Table 5]
Comparison of mean cheek flexibility (in cm) between Omega 3 and Spirulina group at different time intervals using independent Student t-test.
The mean measurement of cheek flexibility between-group comparison using the independent t-test shows no significant difference exists between Omega 3 and Spirulina groups at various time intervals (p > 0.05).
The comparison of mean difference in burning sensation between omega 3 group and spirulina group at different time intervals using post hoc test.
The multiple mean comparisons by ANOVA and Bonferroni's correction showed a statistically significant difference between the baseline and the subsequent visit (p < 0.05).
The mean difference between all the groups showed statistical significance (p < 0.05) except between the 3rd and 6th months.
Intergroup comparison of VAS for burning sensation [Table 6]
|Table 7: Staging of OSMF (According to Haider's Clinical and functional staging of OSMF)|
Click here to view
Comparison of mean VAS scores for burning sensation between Omega 3 and Spirulina group at different time intervals using independent Student t-test
The mean VAS scores for burning sensation between-group comparison using the Independent t-test shows no significant difference exists between Omega 3 and Spirulina groups at a various time interval (p > 0.05)
Patients of both the groups were followed up every month for three months and then after six months.
| Discussion|| |
A wide array of treatment methods are being implemented for OSMF. In this present study, we have compared the effectiveness of Omega-3 fatty acids and Spirulina in the management of OSMF. Patients in both group A and group B were in the age range of 24-65 years. Out of 40 patients, 80% were males and 20% females, showing male predominance of the condition similar to other studies.
Several studies have been reported anti-inflammatory effects of cod liver oil in patients with Rheumatoid arthritis, due to decreased LTB4 production by neutrophils and monocytes, decreased PGE 2 production by mononuclear cells, decreased IL-1 production by monocytes, decreased plasma IL-1b concentrations, decreased serum C-reactive protein concentrations, and normalization of the neutrophil chemotactic response.
Other studies have also investigated the beneficial effects of Omega 3, polyunsaturated fatty acids eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) on chronic inflammatory diseases including rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel diseases, chronic periodontitis and recurrent aphthous stomatitis.,,,, It is also shown to have anti-inflammatory and antineoplastic activity with minimum side effects.
Dexamethasone in OSMF acts as an immune suppressive agent by its antagonistic activity on the soluble factors released by the sensitized lymphocytes succeeding the activation by nonspecific antigens. It additionally muzzles the inflammatory reaction. Thus, fibrosis is prevented by decreasing fibroblastic proliferation and deposition of collagen. By breaking down hyaluronic acid, Hyaluronidase lowers the viscosity of intercellular cement substances and makes way for other drugs' diffusion. Better results were observed concerning trismus and fibrosis.
A preliminary study was done by Raizada MK. et al. to assess the efficacy of systemic Omega-3 in OSMF patients. They concluded that Omega-3 fatty acids could be used as an adjuvant treatment for OSMF in reducing subjective symptoms.
In a recent trial by Khouli et al., a daily Omega-3 regimen therapy for treating and managing patients with recurrent aphthous stomatitis has shown promising results. Which authors attributed to the ability of EPA and DHA to alter cellular functions of polymorphonuclear leukocytes (through regulating the trafficking of inflammatory cells to the sites of inflammation and blocking proinflammatory cytokine production), modulate lymphocyte proliferation, and significantly increase the activities and mRNA expression of endogenous host antioxidant enzymes including glutathione peroxidase, superoxide dismutase, and catalase, thus enhancing the clearance of inflammation within the lesion to promote tissue regeneration.
One more study by Nikolakopoulou Z et al. showed that n-3 PUFA, EPA, and DHA selectively inhibit the growth of premalignant and malignant keratinocytes compared with their normal or immortalized counterparts, pointing out that Omega 3 might play a role in preventing the conversion of premalignant lesions to malignancy.
Studies were conducted to assess the efficacy of Spirulina as an antioxidant adjuvant to corticosteroid injection, Pentoxyfilline, aloe vera, oxitard, and lycopene in the management of OSMF; They concluded that spirulina is an effective treatment in managing OSMF. The drug showed a significant reduction in the burning sensation and mouth opening; spirulina's potent anti-inflammatory and antioxidant properties. The chemopreventive capacity to reverse potentially malignant lesions of spirulina is attributed to the antioxidant property of a high amount of betacarotene and superoxide dismutase.
Omega 3 helps reduce inflammation by altering the cellular functions of polymorphonuclear leukocytes. Also, it completely inhibits the production of arachidonic acid metabolites by cyclo-oxygenase and lipo-oxygenase pathways, limiting tissue damage.
Restriction of mouth opening is a major disability associated with OSMF. To date, no treatment protocol can restore the mouth opening to normal, but an improvement of a few millimeters has been seen. In our study, mouth opening improvements were seen in both groups and were statistically significant (p < 0.05). Improvement was seen in every subsequent visit. Improvements in tongue protrusion were seen in every subsequent visit, but it was not statistically significant.
Improvements in cheek flexibility were seen in every visit and were statistically significant from 1st visit and 3rd month, 1st visit and 6th month follow-up. Out of 40 patients, 6 patients showed a complete reduction in the burning sensation at the end of the visit, 2 patients in the Omega 3 group, and 4 in Spirulina group.
These improvements in this study in all 4 parameters could be due to the synergistic effect of the drugs.
When the efficacy was compared between two drugs, statistically insignificant results were found for mouth opening, tongue protrusion, cheek flexibility, and burning sensation, which suggests that both drugs were equally efficient.
Only a single study was previously done to determine the effectiveness of Omega-3 fatty acids on OSMF. A comparison of Omega-3 fatty acid and Spirulina in the treatment of OSMF has not been studied before.
Limitation and future aspects
The limitation of our study was the relatively smaller size and no long-term follow-up.
Further studies should be planned with large sample size and longer follow-ups to study the clinical effects of OSMF. Also, the effect of Omega 3 should be studied at the molecular level in vitro. Although multicentric studies should be done for more standardization and better outcome.
| Conclusion|| |
The present study was the first of its kind in which Omega 3 and Spirulina had been compared together in OSMF patients. Intergroup comparison showed improvement in mouth opening, cheek flexibility, and VAS burning sensation except for tongue protrusion. When the efficacy was compared between two drugs, statistically insignificant results were found.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Pindborg JJ. Oral submucous fibrosis is a precancerous condition. J Dent Res 1966;45:546-53.
More C, Gupta S, Joshi J, Varma S. Classification system of oral submucous fibrosis. J Indian Acad Oral Med Radiol 2012;24:24–9. [Full text]
Gupta PC, Warnakulasuriya S. Global epidemiology of areca nut usage. Addict Biol 2002;7:77–83.
Aziz SR. Coming to America: Betel nut and oral submucous fibrosis. J Am Dent Assoc 2010;141:423-8.
Raizada MK, Sable DM, Chowdhery A, Chavan MS, Rajpurohit LS. Omega 3: A novel treatment agent in oral submucous fibrosis: A pilot study. J Oral Pathol Med 2017;46:439-42.
Haider SM, Merchant AT, Fikree FF, Rahbar MH. Clinical and functional staging of oral submucous fibrosis. Br J Oral Maxillofac Sur. 2000;38:12-5.
Calder PC. Session 3: Joint Nutrition Society and Irish Nutrition and Dietetic Institute Symposium on 'Nutrition and autoimmune disease' PUFA, inflammatory processes and rheumatoid arthritis. Proc Nutr Soc 2008;67:409–18.
Calder PC. Polyunsaturated fatty acids, inflammatory processes and inflammatory bowel diseases. Mol Nutr Food Res 2008;52:885-97.
Elkhouli AM. The efficacy of host response modulation therapy (omega-3 plus low-dose aspirin) as an adjunctive treatment of chronic periodontitis (clinical and biochemical study): A randomized, double-blind, placebo-controlled study. J Periodont Res 2011;46:261-8.
Kremer JM, Lawrence DA, Jubiz W. Dietary fish oil and olive oil supplementation in patients with rheumatoid arthritis. Arthritis Rheumatol 1990;33:810-20.
Khouli AE, Gendy EA. Efficacy of omega-3 in the treatment of recurrent aphthous stomatitis and improvement of quality of life: A randomized, double-blind, placebo-controlled study. Global J Health Sci 2014;117:191-6.
Nagaraj T, Okada T, Biswas A, Sahu P, Saxena S. Intralesional injections in oral submucous fibrosis-A series of case reports. J Med Radiol Pathol Surg 2018;5:23–6.
Nikolakopoulou Z, Nteliopoulos G, Michael-Titus AT, Parkinson EK. Omega-3 polyunsaturated fatty acids selectively inhibit growth in neoplastic oral keratinocytes by differentially activating ERK1/2. Carcinogenesis 2013;34:2716–25.
Shetty P, Shenai P, Chatra L, Rao PK. Efficacy of spirulina as an antioxidant adjuvant to corticosteroid injection in the management of oral submucous fibrosis. Indian J Dent Res 2013;24:347-50.
] [Full text]
Mulk BS, Deshpande P, Velpula N, Chappidi V, Chintamaneni RL, Goyal S, et al
. Spirulina and pentoxifylline-A novel approach for the treatment of oral submucous fibrosis. J Clin Diagn Res 2013;7:3048-50.
Patil S, Al-Zarea BK, Maheshwari S, Sahu R. Comparative evaluation of natural antioxidants spirulina and aloe vera for the treatment of oral submucous fibrosis. J Oral Biol Craniofac Res 2015;5:11-5.
Patil, Santosh R.; Maragathavalli, G.; Ramesh, D. N. S. V.; Munishekar, M. S.; Rao, Krishna A.; Alam, Mohammed Khursheed, et al
. Comparative efficacy of newer antioxidants spirulina and oxitard for the treatment of oral submucous fibrosis. Int Med J 2019;26:135-138.
Wadeyar P, Charantimath S, Bagewadi A. Comparison of effectiveness of spirulina and lycopene as an adjuvant to corticosteroid (triamcinolone acetonide) injection in the management of oral submucous fibrosis) –randomized controlled trial. Int J Sci Res 2019;8:9.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]