EFFICACY OF LYCOPENE IN COMBINATION WITH VITAMIN E IN MANAGEMENT OF ORAL SUBMUCOUS FIBROSIS-A CLINICAL PROSPECTIVE STUDY

2. EFFICACY OF LYCOPENE IN
COMBINATION WITH VITAMIN E IN
MANAGEMENT OF ORAL SUBMUCOUS
FIBROSIS-ACLINICAL PROSPECTIVE
STUDY
JOURNAL OF ADVANCED MEDICAL AND DENTAL SCIENCE RESEARCH
I VOL.3I JULY-SEPTEMBER 2015
Presented by – Zareesh.S.Akhtar.

3. INTRODUCTION
•Pindborg in 1966
• an insidious chronic disease affecting in any part of the oral
cavity and sometimes the pharynx.
•Although occasionally preceded by and /or associated with vesicle
formation.
•It is always associated with juxta-epithilial inflammatory reaction
followed by fibro elastic change of lamina propria ,
•while epithelial atrophy leading to stiffness of oral mucosa and
causing trismus and inability to eat.

4. ETIOLOGY
•Capsaicin (chilli consumption)
•Betel nut alkaloids
•Hypersensitivity
•Autoimmunity
•Genetic complex deficiency
•Common is chewing areca nut
•Collagen disorder
•Nutritional deficiency
•Inhibition of collagen
phagocytes
•Chemical carcinogens
•Upregulation of COX-2
inflammatory changes
•Areca alkaloids causing
fibroblast proliferation
In indian subcontinent OSMF is though to be multifactorial

5. •Areca nut chewing is deep rooted in Indian culture used as mouth
freshening agent ,has various symbolic roles throughout Indian
history.
•Alarming fact is this habit is becoming popular among
adolescents ,adult male and female

6. LYCOPENE
•A carotenoid found in tomatoes
•It prevents oxidation of low density lipoprotein
•Its an powerful antioxidant and has a singlet oxygen quenching
ability twice as high as beta-carotene
•Being potent anticarcinogenic demonstrated profound benefit in
precancerous lesions and conditions.
• Lycopene increase GJC between cells and enhances the
expression of connexin 43, and thereby up-regulates GJC and acts
as an anti-carcinogen.

7. VITAMIN E
•Known as tocopherol
•Have antioxidant properties
•Prevents peroxidation of unsaturated fatty acids
•Retards carcinogenesis by maintaining the number of Langerhans
cells
•It possess anti-inflammatory properties.
•Vitamin E is an effective stimulant of humoral immune response

8. AIMS & OBJECTIVE
•Various tratment modalities ranging from conservative treatment to surgical
procedures have been attempted.
•Aim was to elucidate the role of lycopene in combination with vitamin e in
management of OSMF, this study is conducted.

9. MATERIALAND METHOD
•This was a clinical prospective study conducted between March 2015
and July 2015 on total of 90 patients,
• Who visited the Department of Oral Medicine and Radiology, Vyas
Dental College & Hospital, Jodhpur, Rajasthan, India,
• Patient selected for the study, where oral submucous fibrosis was
confirmed both clinically and histologically.
•Of these, 72 patients successfully completed the trial and reported for
follow-up

10. •The aim and purpose of the study was explained to each
patient and written consent was obtained.
•The habits like tobacco chewing and ethanol usage were
assessed on each visit and the patients were encouraged to
discontinue the habit.
•These 72 patients were randomly categorized (irrespective of
the size and severity of the lesions) into 3 groups:

11. •Group A (Lycopene Group): 24patients were treated with 8
mg of lycopene in two equally divided doses. The product
used in the study was soft gel Lycored TM, Jagsonpal
Pharmaceuticals, New Delhi
•Group B (Lycopene + Vit. E Group): 24 patients were
treated with 8 mg of lycopene + vitamin E (400 I.U.) +
selenium (200 mcg) in two equally divided doses. The
product used was LYC-O-MATO soft gels, manufactured by
Mano pharmaceuticals, Chennai, India.
•Group C (Placebo Group): 24 patients were given placebo
capsules once daily.

12. DATA COLECTION
•Patients were evaluated every 15 days during the treatment
period of three months.
•Patients were followed up for two months.
• The main parameters assessed were improvements in
mouth opening a in mm and burning sensation
•By visual analog scale (VAS) from 1 to 10.

13. •The two parameters were recorded weekly for 2 months.
•One-way ANOVA followed by post hoc Tukey’s test for
group-wise comparisons were used.
• During each visit, the patients were examined for presence
or absence of erythematous areas/ulceration/erosions,
burning sensation and mouth opening.

14. Results
Distribution of oral submucous fibrosis patients in three group.

15. There was significant improvement in mouth opening in patients
subjected to lycopene as compared to placebo group. (Table 1, 2
and 3)

18. Patients also showed reduction in burning sensation and
erythematous/ ulceration/ erosions. (Table 4,5 and 6)

21. Discussion
•Gupta S et al observed there was significant reduction of vitamin
E in stage II and III OSMF .
•Which reflects increase in oxidative stress in progression of
OSMF
•So a newer antioxidant like lycopene in combination with vitamin
E with more potent properties is used in present study

22. •Lai DR et al stated that B vitamins was ineffective in improving
trismus
•Karemore et al observed improved mouth opening of 69.56%
with lycopene group
•Whereas Maher et al observed less improvement (41%) in
mouth opening using multiple micronutrients.

23. CONCLUSION
• Present study showed better tolerance to spicy food and burning
sensation along with absence of erythematous areas or ulcerations
or erosions
• In LYCOPENE with VITAMIN E group as compared to
LYCOPENE and PLACEBO group
•Lycopene in combination with vitamin E is a highly efficacious
drug in the management of oral submucous fibrosis which is
proven to be safe and reliable treatment method .

24. SUMMARY
1 group
24 people
Lycopene &
cessation of
habit
75%
Improvement in
mouth opening
2 group
24 people
Lycopene +vitamin
E & cessation of
habit
83% improvement
in mouth opening,
Burning sensation
ulcerations
3 group
24 people
Placebo drug &
cessation of
habit
60%
Improvement in
mouth opening
The study group included 72 patients with OSMF

25. CROSS REFERENCE

26. Clinical evaluation of different treatment methods for
OSMF.A10-year experience with 150 cases .J Oral Pathol
Med.1995 Oct;24(9):402-6
Lai DRI,Chen HR,Lin LM,Huang YL,Tsai CC

27. AIM & OBJECTIVE
•Aim was to evaluate the different treatment methods(surgical &
Medical)
•In the management of early and advanced cases of OSMF over
past 10 years with 150 cases
•And proposed a effective regime for the treatment of OSMF.

28. Material & Method
•Over 10-year period total 150 patients (M=145 &
F=5)suffering from OSMF diagnosed clinically and
pathologically were treated at the Kaohsiung medical college
& hospital ,Taiwan.
•These 150 patients were divided into2 groups with varying
degree of OSMF were treated by either Medical or Surgical
Therapies

29. •Over 10 year period a total of 150 patients divided into two
groups with varying degree of OSMF
•Treated by
1-medical treatment group
2-surgical treatment group

30. •Medical treatment group involved patients with IID 20mm to >35
and were further divided into subgroups as follow (each group
containg 25 patients).
•Subgroup A-conservative oral administration of vitamin B complex
200mg B.D
•- buflomedial hydrochloride 400mg TDS and
•- topical triamcinolone acetonide 0.1% at bedtime

31. •Subgroup B-conventional submucosal injections of a
combination of
•- dexamethasone(4mg/ml) and
•-2 part hyaluronidase 200USP unit/ml diluted in 1.0ml of
2% xylocaine by 27 gauge dental needle.
•-Not more than 0.2ml solution /site for 20 weeks.
•Subgroup C-a combination of both (a) and (b).

32. •The surgical group included patient with IID <20mm and were
further divided into subgroups (each group containg 25 patients)
,was treated by the excision of fibrotic tissues and covering defect
with -
•Subgroup D Split thickness skin graft harvested from patients
thigh skin
•Subgroup E Fresh human amnion
•Subgroup F Buccal fat pad graft (BFP)

33. Result

34. o Subgroup A patients were quickly relieved by ulcerations
,burning sensations but there was no improvement in trismus
o Subgroup B patients felt relief from stiffness of buccal
mucosa ,ulcerations ,burning sensation ,trismus
o Subgroup C patients who were treaded by both 1+2 had early
and marked relief from symptoms

36. o In surgical group interincisal mouth opening was less than
20 mm after surgical intervention mouth opening achieved
was 30-35 mm
o But there was decrease in interincisal distance up to 5-
10mm after 2 year of follow up
o Grafts and wounds contracted in all patients by varying
amount .

37. Conclusion
•Subgroup A only provided symptomatic relief from ulcerations and
other lesions
•But not trismus it can be used as an adjuvant to other treatment
modes but cannot be used alone.
•Treatment course of subgroup B and C showed little difference in
improvement in trismus
• Subgroup B by 83% & Subgroup C by 86% at the end of
treatment course.

38. •During the 2 year follow up there was only 3-5mm range decrease in
interincisal distance which is less then surgical group and acceptable
.
•After surgical intervention mouth opening achieved was 30-35 mm
•But there was decrease in interincisal distance up to 5-10mm after 2
year of follow up as grafts and wounds contracted in all patients by
varying amount .

39. •Subgroup C treatment , and Surgical interventions proved to
be useful to manage OSMF in early and advanced stages of
progression.

40. Efficacy of lycopene in the management of OSMF
Oral Surg Oral Med Oral Pathol Oral Radio Endod
2007 ;103:207-13
Kumar A, Bagewadi A , keluskar V , Singh M

41. AIM & OBJECTIVES
To evaluate the efficacy of oral lycopene therapy in patients
with oral submucous fibrosis and to compare these effects
with a placebo.

42. MATERIAL & METHOD
•Total of 58 patients with OSMF were included for study
•The study population was randomly divided into 3 groups
•GROUPA -received 16 mg of lycopene( n=21)
•GROUP B - received 16mg of lycopene along with
biweekly intralesional steroid injections( n=19)
• GROUP C - given placebo drugs ( n=18)
Datacollection
•Paried and Unparied t test were used for statistical
evaluation.

43. RESULT
•Mouth opening for patients showed an average increase of
•3.4 mm in group A
•4.6mm in group B
•0.0mm in group C
•These values were statistically found to be highly significant

44. CONCLUSION
The observed effects suggest that lycopene can and should be
used as a first line of therapy in the initial management of oral
submucous fibrosis.

45. LYCOPENE IN THE MANAGEMENT OF OSMF
Asian journal of pharmaceutical and clinical research VOL 6 Issue
3;2013
NIRANZENA PANNEER SELVAM,ARJUN ANAND DAYANAND

46. AIM & OBJECTIVE
The aim of the study was to evaluate the efficacy of oral
lycopene therapy when used in combination with
conventional intralesional steroid therapy in the management
of oral submucous fibrosis.

47. MATERIAL & METHOD
•Totally 45 patients with signs and symptoms of OSF were recruited
for the study from the Department of Oral Medicine and
Radiology, Tamilnadu Government Dental College and Hospital,
Chennai, India.
•The Institute’s Ethical Committee approval was obtained.

48. INCLUSION CRITERIA
•History of the habit of chewing
arecanut or any commercial
products.
• Burning sensation on eating
spicy food.
• Restricted mouth opening with
or without palpable vertical
fibrous bands on the buccal
mucosa Stiffness and blanching
• Without tongue involvement -
Grade III and IV
EXCLUSION CRITERIA
•Patients with histologically proven
OSF turning into malignancy were
excluded from the study

49. •Informed consent was obtained from all the patients.
•Patients were explained about the disease condition and its
premalignant potential.
• The patients were counselled to stop the habit of using arecanut in
all its forms.
•Complete oral prophylaxis was done to improve the oral hygiene
as well as to motivate the patient to stop the habit.

50. •The patients were then randomly divided into three groups (A, B and
C) consisting of 15 cases each.
•Group A patients were given
-oral Lycopene capsules 16 mg (Lycostar®, Mankind Pharma
Ltd., New Delhi, India), one capsule/day. . Lycostar contains
Lycopene 5000 μg along with various micronutrients.
- Along with bi-weekly intralesional injections of Dexamethasone
1.5 ml & Hyaluronidase 1500 IU mixed with lignocaine

51. •Group B patients were given
-oral antioxidant capsules (Multivitamin A-Z soft capsules,
PrimePharm, Shangai, China), one capsule/day
-along with bi-weekly intralesional injections of Dexamethasone
1.5 ml & Hyaluronidase 1500 IU mixed with lignocaine.
• Group C patients were given bi-weekly intralesional injections of
Dexamethasone 1.5 ml & Hyaluronidase 1500 IU with lignocaine
alone without any other oral supplements.

52. RESULT
There was significant increase in mouth opening among all
the 3 groups. The results were statistically significant
between Group A and C and Group B and C.

53. CONCLUSION
• Lycopene in combination with intralesional steroids and
Hyaluronidase.
• Is highly efficacious in improving the mouth opening and
reducing other symptoms in patients with Oral Submucous
Fibrosis.
• No side effects were reported with its usage.

54. Levamisole and antioxidants in the management
of oral submucous fibrosis: A comparative study
Vasanti Jirge, M.C. Shashikanth, I.M. Ali, Nisheeth
Anshumalee Department of Oral Medicine and Radiology,
College of Dental Sciences, Davangere-577 004, India

55. AIM & OBJECTIVE
This study was carried out to evaluate the clinical effects of
levamisole (VERMISOL), and antioxidants (ANTOXID)
and its effect on serum immunoglobulins IgG, IgA and IgM.

56. MATERIAL & METHOD
•The present randomized, single blind study was conducted
in the Department of Oral Medicine and Radiology,
Department of Oral Pathology, College of Dental Sciences,
Davangere and Department of Microbiology, Maratha
Mandal Dental College, Belgaum.
•The study group comprised 45 OSMF patients of

57. •Patients who were healthy and well oriented in time, space and as
a person, patients who satisfied the characteristic clinical features
of OSMF with histopathologic confirmation.
• Patients who agreed to the biopsy, blood and immunological
examination and patients who were willing for follow-up visits, and
those who were willing to quit the habit of chewing areca nut/
gutkha/ and tobacco in any form were included in the study.
Inclusion criteria

58. Exclusion criteria
Patients with OSMF and any past or present systemic
diseases (e.g. diabetes, hypertension, liver disorders or
kidney diseases, autoimmune disorders), other mucosal
lesions, patients suffering from acute or chronic infection,
patients with a known allergy or contraindication to the
study drugs were excluded from the study

59. •Patients were randomly assigned into three groups.
• There were 15 patients in each group
• Group I patients received levamisole, 50 mg three times
daily for three alternate weeks
•Group II patients received 2 capsules of antoxid daily for six
weeks
•Group III patients received levamisole and antoxid.
• The results were analyzed with paired ‘t’ test and unpaired
‘t’ test

60. The results indicated that levamisole, antoxid and the
combination of levamisole and antoxid showed significant
improvement in mouth opening and reduction in burning
sensation.
Significant reduction of serum IgG, IgA and IgM was seen
in the levamisole group and combination group
whereas in the antoxid group significant reduction was
observed only in serum IgA and IgM
RESULT

61. Levamisole can bring about clinical improvement and is
better than antoxid and the combination regimen. The
addition of antoxid to the treatment regimen does not seem
to have an added advantage over levamisole alone.
CONCLUSION