|Year : 2010 | Volume
| Issue : 4 | Page : 508-510
Efficacy of alpha lipoic acid in adjunct with intralesional steroids and hyaluronidase in the management of oral submucous fibrosis
Prasanna Kumar Rao
Department of Oral Medicine and Radiology, Yenepoya Dental College, Yenepoya University, Mangalore, India
|Date of Web Publication||24-Feb-2011|
Prasanna Kumar Rao
Department of Oral Medicine and Radiology, Yenepoya Dental College, Yenepoya University, University Road, Nithyananda Nagar Post, Deralakatte, Mangalore 575018
Source of Support: None, Conflict of Interest: None
Background and Objectives: Oral submucous fibrosis (OSF) is a chronic irreversible condition of the oral mucosa with proven malignant potential. However, till date, there has been a dearth of effective management strategies. This study used alpha lipoic acid, an antioxidant, in oral form to determine if it could be useful in managing OSF patients.
Materials and Methods: A case-control study was conducted on 18 patients of OSF (9 cases and 9 controls). The case group was treated using alpha lipoic acid in addition to the intralesional steroid and hyaluronidase injections used in the control group.
Results: The cases in the alpha lipoic acid group exhibited better relief of symptoms such as burning sensation of the mucosa and mouth opening, as compared to the controls. The use of alpha lipoic acid along with intralesional steroids and hyaluronidase caused reversal of higher clinical stages to lower ones.
Conclusion: The use of an antioxidant, alpha lipoic acid, along with conventional therapy of intralesional steroid injections definitely seems to have a beneficial impact in the management of OSF.
Keywords: Alpha lipoic acid, antioxidant, oral submucous fibrosis, thioctic acid
|How to cite this article:|
Rao PK. Efficacy of alpha lipoic acid in adjunct with intralesional steroids and hyaluronidase in the management of oral submucous fibrosis. J Can Res Ther 2010;6:508-10
|How to cite this URL:|
Rao PK. Efficacy of alpha lipoic acid in adjunct with intralesional steroids and hyaluronidase in the management of oral submucous fibrosis. J Can Res Ther [serial online] 2010 [cited 2021 Jun 13];6:508-10. Available from: https://www.cancerjournal.net/text.asp?2010/6/4/508/77087
| > Introduction|| |
Oral submucous fibrosis (OSF) is a peculiar, chronic progressive, insidious, irreversible, crippling disease of the oral cavity characterized by fibrotic change and severe burning sensation with restricted opening of the mouth. OSF is a condition found among people who chew areca nut. This chewing habit has become an addictive compulsion, in spite of it being non-nutritive as well as a known risk factor for oral cancer. In recent years, chewing processed areca nut preparations available commercially (gutkha/pan masala) has become fashionable amongst the youth. Wide media publicity accorded in their marketing attracts teenagers and younger generations, leading to widespread gutkha use, and consequently, manifestations of OSF are on the rise.
Antioxidants restrict the damage caused by reactive free radicals to cells and cellular components. Diseases where antioxidant therapy is beneficial include diabetes mellitus, inflammatory diseases and for the prevention of chronic processes such as atherosclerosis and carcinogenesis. Antioxidants have been used as supplemental therapy in a variety of oral mucosal disorders and for cancer prevention.  OSF, a precancerous oral condition, has no universally agreed treatment modality because no definite cure has been found. Therefore, this study was conducted to assess the efficacy and tolerability of antioxidant therapy in the treatment of OSF.
| > Objective|| |
The objective of this study was to determine the role of alpha lipoic acid in the management of OSF patients.
| > Materials and Methods|| |
A case-control study was designed and conducted in our institute after the protocol was approved by the ethical committee for conducting studies on human subjects of our institution. The study consisted of totally 18 patients clinically diagnosed and biopsy confirmed as OSF according to the described criteria.  Patients with other oral mucosal disorders, systemic disorders or those not willing to participate in the study were excluded. Written consent was obtained from each patient to participate in the study. The patients were then randomly divided into two groups of nine each, the cases (group I) and controls (group II). Each subject was interviewed in detail, with particular reference to the types, frequency and duration of oral abusive habits, followed by a clinical examination. The burning sensation reported by patients at the presenting visit as well as subsequent follow-up visits was recorded using a 10-point visual analogue scale (VAS). Before beginning the intervention, all the patients were counseled to stop the oral abusive habits.
Group I: Patients in this group were treated with a combination of steroid injection of betamethasone 1 ml and hyaluronidase 1500 IU, given intralesionally, weekly once by multiple puncture method for 12 weeks. An oral antioxidant, alpha lipoic acid, was administered once daily for 3 months.
Group II: Patients in this group were treated with only a combination of steroid injection of betamethasone 1 ml and hyaluronidase, given intralesionally, once a week by multiple puncture method for a period of 12 weeks. This group was not prescribed the antioxidant alpha lipoic acid and therefore served as the control group.
Each patient from both the groups was evaluated fortnightly for mouth opening and burning sensation. After 6 months of the initial diagnosis, a post-treatment biopsy was obtained to compare the histological status with pretreatment records.
The data obtained from the procedures were tabulated and analyzed using statistical methods (Mean, Standard deviation, Kruskal Wallis test, Wilcoxon signed-rank test and Chi-square test).
| > Results|| |
In the study group, the age of subjects ranged from 19 to 52 years, with the maximum number of patients in the third decade of life. Out of 18 patients, only 2 were females and the other 16 were males. All the patients in the study reported chewing areca nut, either in the form of "paan" or betel quid made by rolling raw areca nut and slaked lime in the leaf of the vine piper betel, or used "gutkha/paan masala", a commercial preparation of processed areca nut. Majority of the patients had the habit of chewing gutkha (66%), while 28% chewed paan and only 6% chewed raw areca nut. 38.9% of patients had the chewing habit for less than 5 years (seven patients), 33.3% for 6-10 years and 27.8% patients had it for more than 10 years. The frequency of daily practice varied from 5 times a day upto 13 times a day.
Out of 18 patients, 2 had stage I (11.2%), 11 stage II (61%) and 5 had stage III (27.8%) OSF.
In group I, i.e., alpha lipoic acid group, burning sensation reduced during the treatment and the mean difference in pretreatment and post-treatment values was 3.66 (1.5811); the difference was highly significant (P = 0.008). Mouth opening also increased during treatment and mean difference in values of pretreatment and post-treatment period was 5.55 (SD 3.39) with a highly significant P-value of 0.008. In group II, i.e., non alpha lipoic acid group, the burning sensation reduced during the treatment and mean difference in pretreatment and post-treatment values was 3.33 (2.0616), showing statistically significant difference (P = 0.011). Mouth opening also increased during the treatment and mean difference in values of pretreatment and post-treatment period was 6.33 (3.6827), showing a highly significant difference (P = 0.008) [Table 1].
|Table 1: Pretreatment and post-treatment clinical improvements within both the groups|
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When the overall paired differences between the two groups were derived, all the values were significant in group I (alpha lipoic acid group); however, in group II (non alpha lipoic acid group), only the mouth opening and burning sensation parameters showed a significant difference.
In group I, before treatment, one patient had stage I OSF (11.1%), five patients had stage II OSF (55.6%), and three patients had stage III OSF (33.3%). After treatment, six patients had stage I OSF (66.7%), three patients had stage II OSF (33.3%) and none had stage III OSF (0%). Therefore, after treatment, four patients with stage II and one patient with stage III OSF had stage I OSF. Also, two patients with stage III OSF had stage II OSF after treatment. In paired sample test, P-value was calculated to be 0.029, which is statistically significant [Table 2]. In group II, before treatment, one patient had stage I OSF (11.1%), six patients had stage II OSF (66.7%), and two patients had stage III OSF (22.2%). After treatment, five patients had stage I OSF (55.6%), three patients had stage II OSF (33.3%) and one patient had stage III OSF (11.1%). Thus, post-treatment, three patients with stage II OSF and one patient with stage III OSF had stage I OSF. Also, one patient with stage III OSF had stage II OSF after treatment. Interestingly, one patient turned to stage III OSF from stage II OSF in spite of the treatment. The paired sample test revealed P = 0.135 (statistically nonsignificant) [Table 2].
|Table 2: Alpha lipoic acid group pretreatment and posttreatment stage changes|
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| > Discussion|| |
All the available treatments for OSF provide only symptomatic relief to the patients. In this study, an attempt was made to evaluate the efficacy of oral antioxidant therapy using alpha lipoic acid. All the 18 patients comprising the study population had age ranging from 19 to 52 years, with majority of the patients in the third decade of life, similar to other reported studies. , A big proportion of the patients chewed processed areca nut, an indication of popularity of these commercially available products in comparison to the traditionally chewed betel quid, a change in lifestyle and peer pressure leading to adoption of the habit at a younger age. A definite male predilection seen in our patients is consistent with the recent findings,  which points to the fact that the addiction to processed areca nut preparations and also the chewing habit is not looked down upon in the male peer group as much as in females.
Alpha lipoic acid (also called thioctic acid) has been claimed to be the near-perfect antioxidant. It has been researched for its use in the treatment of HIV infection and in diabetic patients based on the property of dissolution in both water and fat. , Alpha lipoic acid is able to scavenge more wayward free radical cells than most other antioxidants, the majority of which tend to dissolve in either fat or water but not both. 
A significant decrease has been noted in beta-carotene and vitamin E in serum of OSF patients.  A 6-week oral administration of beta-carotene and vitamin E caused increase in plasma level of these two antioxidants along with decrease in malonaldehyde (lipid peroxidation product) level associated with clinical improvement. Similar findings have been observed in this study too, wherein there has been a definite improvement in the symptoms, notably, the burning sensations in the oral mucosa and mouth opening values. The improvement in the symptoms also reinforces the efficacy of the therapy to the patients. The patients who were diagnosed to have higher stages of OSF manifestation at inclusion were found to have a lower stage of OSF at the end of the study, a statistically significant observation. The patients in the control group did not exhibit such a stark difference that can only be attributed to the addition of alpha lipoic acid in the therapy of group I patients, the only attribute different from the control group. This clearly demonstrates the beneficial impact of having included the antioxidant in the therapy of the cases group. This finding emphasizes the role of nutritional factors in the etiology as well response to treatment. A clinical trial in India suggested that lycopene can and should be used as a first-line therapy in the initial management of OSF.  Simultaneously, some researchers are critical about the role of antioxidants in the progressive stage of the disease.  Others suggest lack of reliable evidence for the effectiveness of any specific intervention for the management of OSF, illustrated by the paucity and poor methodological quality of clinical trials.  The antioxidant, alpha lipoic acid, has a definitive protective role as demonstrated in this study, and it can certainly be recommended for clinical use.
| > References|| |
|1.||Shklar G. Mechanisms of cancer inhibition by anti-oxidant nutrients. Oral Oncol 1998;34:24-9. |
|2.||Bailoor DN, Nagesh KS. Fundamentals of oral medicine and radiology. 3 rd ed. New Delhi: Jaypee Bros; 2005. p. 282-9. |
|3.||Haider SM, Merchant AT, Fikree FF, Rahbar MH. Clinical and functional staging of oral submucous fibrosis. Br J Oral Maxillofac Surg 2000;38:12-5. |
|4.||Paissat DK. Oral submucous fibrosis. Int J Oral Surg 1981;10:307-12. |
|5.||Dayal PK, Subhas BG, Shah R. Oral submucous fibrosis a field study among betel nut chewers. Karnataka State Dent J 1996;16:12-5. |
|6.||Baur A, Harrer T, Peukert M, Jahn G, Kalden JR, Fleckenstein B. Alpha-lipoic acid is an effective inhibitor of human immuno-deficiency virus (HIV-1) replication. Klin Wochenschr 1991;69:722-4. |
|7.||Ziegler D, Reljanovic M, Mehnert H, Gries FA. Alpha-lipoic acid in the treatment of diabetic polyneuropathy in Germany: Current evidence from clinical trials. Exp Clin Endocrinol Diabetes 1999;107:421-30 |
|8.||Hughes DA. Dietary carotenoids and human immune function. Nutrition 2001;17:823-7. |
|9.||Gupta S, Reddy MV, Harinath BC. Role of oxidative stress and antioxidants in aetiopathogenesis and management of oral submucous fibrosis. Indian J Clin Biochem 2004;19:138-41. |
|10.||Kumar A, Bagewadi A, Keluskar V, Singh M. Efficacy of lycopene in the management of oral submucous fibrosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;103:207-13. |
|11.||Kerr AR. Efficacy of oral lycopene in the management of oral submucous fibrosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;103:214-5. |
|12.||Fedorowicz Z, Chan Shih-Yen E, Dorri M, Nasser M, Newton T, Shi L. Interventions for the management of oral submucous fibrosis. Cochrane Database Syst Rev 2008;4:CD007156. |
[Table 1], [Table 2]
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