|Year : 2016 | Volume
| Issue : 3 | Page : 133-138
Coenzyme Q10 as a dietary supplement combined with topical corticosteroids in the treatment of erosive lesions of oral lichen planus
Malak Y Shoukheba1, Enas A Elgendy2
1 Oral Medicine, Periodontology, Oral Diagnosis and Radiology Department, Faculty of Dentistry, Tanta University, Tanta, Egypt
2 Oral Medicine, Periodontology, Oral Diagnosis and Radiology Department, Faculty of Dentistry, 6th October University, Egypt
|Date of Submission||21-May-2016|
|Date of Acceptance||15-Jun-2016|
|Date of Web Publication||29-Sep-2016|
Malak Y Shoukheba
Oral Medicine, Periodontology, Oral Diagnosis and Radiology Department, Faculty of Dentistry, Tanta University, Tanta
Source of Support: None, Conflict of Interest: None
Introduction: Oral lichen planus (OLP) is a chronic mucocutaneous disease with an immunological etiology. This study was conducted to evaluate the effect of coenzyme Q10 (CoQ10) as an adjunctive to topical corticosteroids in the treatment of erosive–ulcerative lichen planus.
Materials and methods: A total of 30 patients with a confirmed clinical diagnosis of OLP participated in this clinical trial. Patients were randomly allocated into one of two groups and treated as follows: group I received topical corticosteroids and group II received CoQ10 combined with topical corticosteroids. Assessment of outcome measures including clinical score and pain was carried out at the time of initial visit (baseline) and at 2, 4, 8, and 12 weeks following treatment protocol. All recorded data were analyzed using paired t-test and independent t-test. The level of significance was established at a P value of 0.05 or less.
Results: The two studied groups showed a marked reduction in pain sensation and size of lesions, particularly in the final follow-up period. However, healing and decrease in the size of the lesions were effective in group II, and a significant difference was found between the two groups favoring group II over group I.
Conclusion: CoQ10 in combination with topical corticosteroids was found to be effective in managing ulcerative lesions of OLP; however, more studies with a larger sample sizes and longer duration with evaluation of the adjunctive effect of CoQ10 on inflammatory markers expressed in OLP are recommended.
Keywords: antioxidant; coenzyme Q10, cortisone, erosive oral lichen planus
|How to cite this article:|
Shoukheba MY, Elgendy EA. Coenzyme Q10 as a dietary supplement combined with topical corticosteroids in the treatment of erosive lesions of oral lichen planus. Tanta Dent J 2016;13:133-8
|How to cite this URL:|
Shoukheba MY, Elgendy EA. Coenzyme Q10 as a dietary supplement combined with topical corticosteroids in the treatment of erosive lesions of oral lichen planus. Tanta Dent J [serial online] 2016 [cited 2017 Jun 22];13:133-8. Available from: http://www.tmj.eg.net/text.asp?2016/13/3/133/191436
| Introduction|| |
Oral lichen planus (OLP) is a relatively common chronic mucocutaneous autoimmune inflammatory disease of the mucosal surface with a variety of clinical manifestations including reticular, papular, hyperkeratotic, atrophic, erosive, and bullous forms . The exact etiology of OLP is still unknown, but it is mostly considered as a multifactorial process with different triggers such as genetic susceptibility, immunological illnesses, malnutrition, and psychological as well as infectious factors ,.
In addition, the level of reactive oxygen species (ROS) and lipid peroxidation may be related to OLP . Any certain condition that leads to increased levels of ROS (either by overproduction or impaired removal) or reduced function of antioxidants is called oxidative stress. ROS may be toxic to cells via inactive enzymes, denaturizing proteins, DNA destruction, and lipid peroxidation. These events lead to damaged cell membrane, increased reactive aldehyde materials, and impaired cell function . This suggests that oxidative stress is a major trigger for OLP, and the level of antioxidants is a potential determinant of susceptibility to be affected by OLP ,.
A variety of treatments have been proposed for OLP: topical or systemic corticosteroids, cyclosporine, retinoids, azathioprine, tacrolimus, pimecrolimus, photochemotherapy, and surgery ,. Systemic and topical corticosteroids are probably the most effective treatment modality for patients with diffuse erosive OLP or multisite disease . Despite the therapeutic effects of corticosteroids, they have significant morbidity and disturbing adverse effects such as fungal infections and adrenal suppression. Moreover, steroid use is contraindicated in patients who are breastfeeding, and have to be used with caution in patients with herpetic infections, glaucoma, HIV infection, tuberculosis, diabetes mellitus, candidiasis, and hypertension, as well as in pregnant women, resulting in a continuing search for novel therapies ,,,.
Coenzyme Q10 (CoQ10) is a member of a family of naturally occurring substances known as quinines , one of the most significant lipid antioxidants, which prevent the generation of free radicals and modifications of proteins, lipids, and DNA , providing protection from oxidative damage that occurs in fat-rich tissues such as cell membranes, protecting membrane phospholipids from peroxidation and cellular oxidative damage ,. The maximal antioxidative power of the CoQ10 coenzyme is credited to its electron-donating properties that neutralize free radicals  and its ability to replenish other valuable endogenous antioxidants . Papucci et al.  demonstrated that CoQ10-mediated antiapoptotic activity might be an essential mechanism for its powerful actions.
Therefore, the aim of the present study was to investigate the efficacy of using CoQ10 in combination with topical corticosteroids in the management of symptomatic erosive–ulcerative lesions of OLP.
| Materials and Methods|| |
This study was conducted in the period from May 2014 to November 2015. A total of 30 patients (21 females and nine males) were selected from the Department of Oral Medicine, Faculty of Dentistry, Tanta University and 6 October University. All participants received full written and verbal information about the study and signed the informed consent form. The study complied with the Helsinki Declaration of 1964, as revised in 2004. There were no conflicts of interest in this study.
- Clinical diagnosis of OLP (presence of painful and atrophic–erosive oral lesions, presence of bilateral, mostly symmetrical lesions, and presence of a lace-like network of slightly raised white lines)
- Age between 30 and 60 years
- Patients who were willing to be enrolled in this study and had the ability to complete the study.
- Pregnant or breastfeeding women (pregnancy test for women of childbearing age)
- Lichenoid reactions caused by certain drugs or dental amalgam
- Therapy for OLP in the 6 months before the study
- Patients without hepatitis C (after the patients' medical histories were recorded, the patients were given hepatic screening as published elsewhere)
- Presence of candidiasis before treatment
- Patients with pre-existing diabetes or an initial random glucose level exceeding 200 mg/dl before initiating steroid therapy
- Hypertensive patients
- Contraindications for corticosteroid use (immunodeficiency or severe hematological alterations).
The enrolled participants, who met the inclusion/exclusion criteria, were randomly divided into two groups:
Group I (15 patients)
The control group received topical corticosteroids therapy alone – triamcinolone acetonide (Kenalog in orabase: Bristol-Myers Squibb, Spain) applied topically four times a day, that is, following each meal and at bed time for 1 month.
Group II (15 patients)
The experimental group included 15 patients who were treated with both topical corticosteroids: triamcinolone acetonide (Kenalog in orabase: Bristol-Myers Squibb) applied topically four times a day, that is, following each meal and at bed time for 1 month, in addition to CoQ10 30 mg capsule (Mepaco-Medifood Enshas El Raml, Sharkeia, Egypt) three/day for 2 months.
The patients were asked to report immediately if there was any side-effect at any time during the study.
Each patient was examined at the beginning of treatment, and then after 2, 4, 8, and 12 weeks of therapy.
The clinical data were scored according to criteria used by Thongprasom et al. :
- Score 5=white striae with erosive area more than 1 cm
- Score 4=white striae with erosive area less than 1 cm.
- Score 3=white striae with atrophic area more than 1 cm
- Score 2=white striae with atrophic area less than 1 cm
- Score 1=mild white striae, no erythematous area
- Score 0=no lesion, normal mucosa.
Pain was scored using the visual analogue scale (VAS), a well-documented method of pain assessment :
The severity of pain and pain sensation were evaluated according to the following scales:
- Scale 0: no pain: VAS=0
- Scale 1: mild pain: 0 < VAS≤3.5
- Scale 2: moderate pain: 3.5<VAS≤7
- Scale 3: severe pain: 7 < VAS≤10.
Patients were asked to score their intensity of pain at each visit. Pain scores ranged from 0 (no pain) to 10 (extreme pain).
All the results were tabulated and statistically analyzed using SPSS software (version 10©; SPSS Inc., Chicago, Illinois, USA). Data were presented as means and SDs. The two study groups were compared using independent samples t-test. Moreover, within each group, paired sample t-test was used to determine significant changes between time points for parametric data. The significance level was set at P value less than 0.05. Data were explored using the Kolmogorov–Smirnov test of normality and were found to have a normal (parametric) distribution. We estimated the sample size according to the expected difference in the clinical score between groups. In a previous pilot study (10 cases for each group), we found that the SD for the control group was 1.2, the SD for the test group was 1.33, and the mean difference between the two groups was 2. Therefore, the calculated minimal sample size was 11 cases in each group with type I error α=5% and power test (1−β)=95%.
| Results|| |
A total of 30 patients (nine males and 21 females) completed the study, 15 in group I with a mean age of 47.33 ± 8.138 and 15 in group II with a mean age of 49.66 ± 5.61 years ([Table 1]). Distribution of age, sign, and symptoms of lesions before treatment were the same in both groups. Most of the cases in the cortisone-treated group reported fungal infection (treated with antifungal drugs), which was not reported among topical cortisone plus CoQ10-treated patients. There were no differences between the experimental groups in lesion size, pain sensation, and severity of lesions at baseline.
[Table 2] shows that both treatment modalities resulted in significant reduction in the mean lesion size at all study evaluation periods as compared with the mean baseline value (P < 0.001) with no statistical significant differences between them at both baseline and 2 weeks of evaluation, whereas there were significant differences in favor of group II at 4 (P < 0.05), 8 (P < 0.01), and12 (P < 0.05) weeks.
|Table 2: Mean values of criteria of clinical data among the study groups at baseline and at 2, 4, 8, and 12 weeks after treatment|
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[Table 3] shows the number of patients in any score before and after treatment in both groups. In group I, 60% (nine) of the patients were under score 4 and 40% (six) were under score 3 at baseline. At 2 weeks, 80% (12) of the patients were under score 2 and 3, whereas 20% (three) of the patients did not show significant improvement and were still under score 4. At 4 weeks, complete remission in 20% (three) of the patients was observed and 80% of them were under score 1 and 2. At 8 weeks, complete remission was observed in 60% (nine) of the patients and partial healing in the other patients (40%) who were under scores 1 and 2 followed by recurrence or relapse of the lesion in 20% (three) of the patients under score 3 at 12 weeks.
|Table 3: Sign scores before and after treatment in each group and recurrence rates|
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On the other hand, in group II, 53% (eight) were under score 4 and 47% under score 3 at baseline. At 2 weeks, 60% (nine) came under score 2, partial healing was observed in 20% (three) with scores under 3, and 20% of the patients remained under score 4. After 1 month, complete remission was observed in 60% (nine) of the patients and partial healing in 40% (six) of the patients under score 1 and 2. Complete remission was observed in 80% (12) of the patients at 8 weeks and partial healing was also observed in 20% (three) under score 1. Complete remission continued up to the end of the study (12 weeks) in 80% of the patients, whereas 20% of the patients came under score 2, indicating that CoQ10 has adjunctive effect to local cortisone therapy in treating patients with erosive OLP.
For ethical purposes, patients with lesions of OLP that did not fully recover during treatment of the present study are still under observation until complete resolution of lesions.
[Table 4] shows the effect of both treatment modalities on the mean VAS score; both treatment modalities led to a dramatic decrease in pain and burning sensation among OLP patients and the change was statistically significant (P < 0.001) as compared with baseline values. The difference between the two groups was not statistically significant (P > 0.05).
|Table 4: Mean scores of visual analogue scales among the study groups at baseline and at 2, 4, 8, and 12 weeks after treatment|
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| Discussion|| |
OLP is a relatively common chronic autoimmune inflammatory disease of the mucosal surface . Pharmacological agents known to reduce the synthesis of interleukin-1 (IL-1) and tumor necrosis factor (TNF-α) include corticosteroids and cyclosporine, both of which have been shown to be effective in managing OLP but have well-known adverse side-effects, particularly with long-term administration . NSAIDs have also been used as an alternative to corticosteroids but with less beneficial results in addition to their known side-effects . We tried to find out a new modality for management of OLP cases with minimum side-effects, especially when glucocorticoid is ineffective or contraindicated.Hence, the aim of the present study was to test the efficacy of using CoQ10 combined with topical corticosteroids in the management of symptomatic erosive–ulcerative lesions of OLP.
Some previous studies have suggested that there is a relationship between high oxidative stress and low antioxidant activity in those who have OLP ,,. In addition, apoptosis or programmed cell death is thought to play a major role in the etiopathogenesis of lichen planus; following an unknown trigger, keratinocytes are subjected to T-cell attack, eventually leading to apoptosis .
In the present study, all the treatment modalities resulted in significant reduction of the mean lesion size and VAS at all study evaluation points as compared with the mean baseline value (P < 0.001), with no statistical significant differences between them.
Both treatment modalities resulted in significant reduction in the mean lesion size at all study evaluation points as compared with the mean baseline value (P < 0.001), and there were significant differences in favor of group II at 4, 8, and 12 weeks. In general, the results of the present study showed a significant intergroup improvement in pain sensation and reduction in lesion size favoring group II over group I, indicating the effectiveness of CoQ10 food supplement as adjunctive to topical cortisone in treatment of OLP.
These results are in accordance with Carbone et al. , who reported the potential therapeutic value of topical corticosteroids in the management of patients with OLP. Moreover, Campisi et al.  demonstrated the therapeutic beneficial effects of topical cortisone in the treatment of OLP.
In group I, complete remission was achieved in 20% of patients at 1 month followed by 60% of the patients at 2 months, which continued up to the end of the study (3 months) with relapse of the lesion in 20% under score 2. On the other hand, group II showed complete remission in 60% of the patients at 1 month and increased up to 80% at 2 months, which was continued up to the end of the study with relapse in 20% of the patients under score 2.
Recent studies have demonstrated a beneficial clinical therapeutic value of CoQ10 as an antioxidant. Battino et al.  reviewed the role of CoQ10 as an important antioxidant in free radical-mediated neurodegenerative diseases. Studies have suggested that CoQ10 also exerts anti-inflammatory properties via IL-1β, TNF-α, and NFκB1-dependent gene expression, thus enhancing clearance of inflammation within the lesion to promote tissue regeneration and wound healing ,. Jin et al.  demonstrated that CoQ10 inhibits the expression of TNF-α and promotes the expression of IL-10 in periodontal tissues of experimental periodontitis rats.
In addition, a preliminary study by Capaccioli et al.  showed that CoQ10 is endowed with antiapoptotic activity as a free radical scavenger. Moreover, Papucci et al. demonstrated that treatment with CoQ10 lowered the number of apoptotic keratocytes in response to excimer laser irradiation to a much higher extent than other free radical scavengers. Moreover, supplemental CoQ10 has good safety record. No adverse effects have been reported with daily dosage ranging from 600 to 1200 mg .
Four cases of acute pseudomembranous candidiasis were found in the group I, which was not reported in group II, and this might be explained by the immunomodulatory effect of CoQ10, as it may have positive effects on immune response, based on its antioxidant effects  ([Figure 1] and [Figure 2]).
|Figure 1: Patient treated with topical cortisone. (a) The buccal mucosa showing erythematous and ulcerative lesions; (b) clinical response after 2 weeks; (c) clinical responses after 4 weeks; (d) clinical response after 12 weeks.|
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|Figure 2: Patient treated with topical cortisone+coenzyme Q10 (CoQ10) (group II): (a) the buccal mucosa showed erythematous and ulcerative change; (b) clinical response after 2 weeks of treatment; (c) clinical responses after 4 weeks; (d) clinical responses after 12 weeks.|
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| Conclusion|| |
Owing to the lack of side-effects among users of the drug and the relative effectiveness of CoQ10 as adjunctive to topical cortisone for the treatment of erosive lichen planus lesions, this drug can be considered as a solution to OLP patients to decrease side-effects of topical corticosteroids (without complications).
The results of the present study suggest a potential therapeutic role of CoQ10 supplement in management of patients suffering from atrophic or erosive lichen planus through its beneficial impact on clinical score and associated pain, and it can be useful as a cortisone-sparing drug to decrease the dose of cortisone as well as its complication.
It is suggested that future studies with larger sample sizes and drug doses should be carried out to test their effectiveness, and any method of treatment for patients with atrophic or erosive lichen planus that helps replace or reduce drug treatment with all its potential side-effects is to be welcomed. The adjunctive effect of CoQ10 on inflammatory markers expressed in OLP may be recommended.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]