Alpha lipoic acid efficacy in burning mouth syndrome. A controlled clinical trial

Background

A double-blind placebo-controlled trial was conducted in order to evaluate the efficacy of alpha lipoic acid (ALA) and determine the statistical significance of the outcome variables. Burning mouth syndrome (BMS) is defined as an oral burning sensation in the absence of clinical signs which could justify the syndrome. Recent studies suggest the existence of neurological factors as a possible cause of the disease.

Material and Methods

60 patients with BMS, in two groups: case group with 600 mg/day and placebo as control group; with follow up of 2 months.

Results

64% of ALA patients reported some level of improvement, with a level of maintenance of 68.75% one month after treatment. 27.6% of the placebo group also demonstrated some reduction in BMS symptoms.

Conclusions

Long-term evolution and the intensity of symptoms are variables that reduce the probability of improvement with ALA treatment. Key words: Burning mouth syndrome, neuropathy, alpha lipoic acid.     

Efficacy of alpha lipoic acid in burning mouth syndrome: a randomized, placebo-treatment study

Summary  To study the efficacy of alpha lipoic acid (ALA) in a group of patients with burning mouth syndrome (BMS). Sixty BMS patients, 30 treated with ALA (Thioderm^®) 800 mg day⁻¹ for 8 weeks and 30 patients on the same protocol with a placebo. The symptomatology was measured on a Visual Analogue Scale (VAS). Sixty patients (54 females and 6 males, mean age 64·37 ± 11·61 years) were included. Thirty-nine patients completed the treatment (23 with ALA and 16 with a placebo). Reviews were carried out at 0, 1 and 2 months. No statistically significant differences were found in the average pre- and post-treatment values for pain with the VAS scores, obtained in the placebo (6·6 ± 2·5 − 2·8 ± 25 = 3·8 ± 3·7) versus ALA (6·3 ± 2·8 − 4·0 ± 2·7 = 2·2 ± 2·6). Only one patient pertaining to the group treated with ALA abandoned because of adverse gastrointestinal side effects. The results showed no significant differences between the two groups.     

Burning mouth syndrome: a systematic review of treatments

Burning mouth syndrome (BMS) is a chronic oral pain syndrome that primarily affects peri‐ and postmenopausal women. It is characterized by oral mucosal burning and may be associated with dysgeusia, paresthesia, dysesthesia, and xerostomia. The etiology of the disease process is unknown, but is thought to be neuropathic in origin. The goal of this systematic review was to assess the efficacy of the various treatments for BMS. Literature searches were conducted through PubMed, Web of Science, and Cochrane Library databases, which identified 22 randomized controlled trials. Eight studies examined alpha‐lipoic acid (ALA), three clonazepam, three psychotherapy, and two capsaicin, which all showed modest evidence of potentially decreasing pain/burning. Gabapentin was seen in one study to work alone and synergistically with ALA. Other treatments included vitamins, benzydamine hydrochloride, bupivacaine, Catuama, olive oil, trazodone, urea, and Hypericum perforatum. Of these other treatments, Catuama and bupivacaine were the only ones with significant positive results in symptom improvement. ALA, topical clonazepam, gabapentin, and psychotherapy may provide modest relief of pain in BMS. Gabapentin may also boost the effect of ALA. Capsaicin is limited by its side effects. Catuama showed potential for benefit. Future studies with standardized methodology and outcomes containing more patients are needed.     

Palliative effect of lafutidine on oral burning sensation

Background:  Lafutidine is a unique histamine H₂-receptor antagonist (H2RA) that has a sensitizing effect on capsaicin-sensitive afferent neurons (CSAN). This effect may make lafutidine useful for the treatment of burning mouth syndrome (BMS).
Methods:  To evaluate the efficacy and safety of lafutidine in patients with oral burning sensation, a randomized controlled trial was performed. Patients who had been receiving other H2RAs with no sensitizing effect on CSAN were randomly assigned to receive lafutidine 10 mg twice daily for 12 weeks, instead of the previous H2RAs, plus gargling with azulene sulfonate sodium (ASS) (lafutidine group, n  = 36) or to continue to receive the previous H2RAs plus ASS gargling (control group, n  = 35). The intensity of burning sensation was scored by means of a visual analog scale (VAS).
Results:  Thirty-four patients in the lafutidine group and 30 in the control group completed the study. In the lafutidine group, the rate of improvement in the VAS score as compared with the baseline value was significant after 4, 8, and 12 weeks of treatment ( P  < 0.05). The improvement rate was consistently higher in the lafutidine group than in the control group; the differences between the groups were significant ( P  < 0.05) after 4, 8, and 12 weeks of treatment. Only two mild abdominal adverse events occurred in the lafutidine group, but neither required the termination of treatment.
Conclusion:  Oral lafutidine is very safe and effective for reducing the intensity of oral burning sensation and may therefore be a viable option for the treatment of BMS.     

Burning mouth syndrome: a review and update

Burning mouth syndrome (BMS) is characterized by the presence of burning sensation of the oral mucosa in the absence of clinically apparent mucosal alterations. It occurs more commonly in middle‐aged and elderly women and often affects the tongue tip and lateral borders, lips, and hard and soft palate. In addition to a burning sensation, the patients with BMS may also complain unremitting oral mucosal pain, dysgeusia, and xerostomia. BMS can be classified into two clinical forms: primary and secondary BMS. The primary BMS is essential or idiopathic, in which the organic local/systemic causes cannot be identified and a neuropathological cause is likely. The diagnosis of primary BMS depends mainly on exclusion of etiological factors. The secondary BMS is caused by local, systemic, and/or psychological factors; thus, its diagnosis depends on identification of the exact causative factor. When local, systemic or psychological factors are present, treatment or elimination of these factors usually results in a significant clinical improvement of BMS symptoms. Vitamin, zinc, or hormone replacement therapy has been found to be effective for reducing the oral burning or pain symptom in some BMS patients with deficiency of the corresponding factor. If patients still have the symptoms after the removal of potential causes, drug therapy should be instituted. Previous randomized controlled clinical trials found that drug therapy with capsaicin, alpha‐lipoic acid, clonazepam, and antidepressants may provide relief of oral burning or pain symptom. In addition, psychotherapy and behavioral feedback may also help eliminate the BMS symptoms.     

A case–control study on etiological factors involved in patients with burning mouth syndrome

Objective:  To evaluate and analyze the risk factors for burning mouth syndrome (BMS).
Methods:  Eighty-seven consecutive patients with BMS and a randomly selected control group ( n  = 82) were comprehensively investigated with a self-designed questionnaire, Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS). A complete blood count and serum sex hormone were also examined in patients with BMS and control subjects. All the data obtained were transferred to a data bank and analyzed statistically in spss 11.5 for windows.
Results:  No statistical difference between the BMS group and the control group was found in blood analyses including white blood cell count, red blood cell count, hemoglobin and platelet count. Among the menopausal or postmenopausal women with BMS, the follicle stimulating hormone (FSH) level was significantly higher, but the estradiol level was significantly lower. The BMS group reported adverse life events more frequently than the control group. Patients with BMS significantly exhibited symptoms of somatization, and both the scores of anxiety, depression in patients with BMS were higher than those of the control group ( P  < 0.05). A regression equation which included six variables had been established by using logistic regression analysis, indicating that the habit of tongue thrusting, lip sucking, periodontitis, smoking, outcome of recent medication, depression were the principal risk factors, among which tongue thrusting was the most significant.
Conclusion:  Our study indicated that BMS may be of psychological origin, and the measures such as refraining from oral parafunctional activities, removing local irritating factors, stopping smoking, good mental health status could help in the prevention of BMS.     

Quality of life in patients with burning mouth syndrome

Objective:  To study the quality of life in patients with burning mouth syndrome (BMS), our primary aim was to compare BMS patients with healthy controls and the secondary aim was to compare subgroups of BMS patients on the type of therapy received; using the Medical Outcome Short Form Health Survey Questionnaire (SF-36) and the Oral Health Impact Profile (OHIP-49) as measurement instruments.
Method:  Sixty consecutive patients (10 males and 50 females) with BMS were studied in the Department of Oral Medicine (Faculty of Medicine and Dentistry, University of Murcia, Spain), while 60 healthy patients were used as controls. The Spanish version of the SF-36 was used to evaluate general quality of life, together with the OHIP-49 in its Spanish version.
Results:  Regarding general quality of life as assessed with the SF-36, and on comparing the BMS vs. the control groups, lower scores were obtained in the former in all domains ( P  < 0.001). The OHIP-49 in turn yielded significant differences in each of the domains vs. the controls. No significant differences were found between the patients with BMS in any domain regarding parafunctional habits and the presence of dentures. In relation to the different treatments, significant differences were recorded in functional limitation ( P  = 0.02) and physical pain ( P  = 0.033).
Conclusion:  Patients with BMS yield poorer scores on all scales vs. the healthy controls when applying the SF-36 and OHIP-49.     

Different therapeutic strategies for burning mouth syndrome: preliminary data

J Oral Pathol Med (2010) 39 : 611–616 Background: To compare different therapeutic supportive approaches in patients with burning mouth syndrome. A prospective study was carried out for this purpose. Materials and Methods: The study involved 56 patients with burning mouth syndrome. They were randomly assigned to treatment with capsaicin, alpha‐lipoic acid or lysozyme‐lactoperoxidase (test drugs) or boric acid (control group). Symptoms were scored after 60 days treatment and 60 days after drug discontinuation. Results: At the end of the treatment period, there was a significant reduction in the symptom scores of all of the patients who received the test drugs (P < 0.01), and at the end of the follow‐up period in the test groups as a whole (P < 0.01); the reduction was not significant when considering each test group separately after the treatment period. All of the treatments were more effective than boric acid and there was no significant difference in the symptom scores of the control group at either of the study time‐points. Conclusions: Our results demonstrate the similar effectiveness of capsaicin and alpha‐lipoic acid in controlling the symptoms of burning mouth syndrome. Lysozyme‐lactoperoxidase may be effective in the supportive care of BMS patients with xerostomia. The transitory effect observed after discontinuing drug administration justifies the use of prolonged therapy in chronically affected patients.     

Burning mouth syndrome (BMS): double blind controlled study of alpha-lipoic acid (thioctic acid) therapy

BACKGROUND: Burning mouth syndrome (BMS) has features of a neuropathy and could be related to the production of the toxic free radicals that are released in stress situations. Alpha-lipoic acid is an antioxidant able to increase the levels of intracellular glutathione and eliminate free radicals. This study aimed to examine the effectiveness of alpha-lipoic acid in the therapy of BMS. METHOD: This was a double blind, controlled study conducted for two months on 60 patients with constant BMS. Comparing alpha-lipoic acid (test) with cellulose starch (placebo), there was no laboratory evidence of deficiencies in iron, vitamins or thyroid function and no hyperglycaemia. RESULTS AND CONCLUSION: Following treatment with alpha-lipoic acid, there was a significant symptomatic improvement, compared with placebo, with the majority showing at least some improvement after 2 months, thus supporting the hypothesis that burning mouth syndrome is a neuropathy. This improvement was maintained in over 70% of patients at the 1 year follow-up.     

Burning mouth syndrome (BMS): controlled open trial of the efficacy of alpha-lipoic acid (thioctic acid) on symptomatology

BACKGROUND: Alpha-lipoic acid (ALA), is a potent antioxidant mitochondrial coenzyme, the trometamol salt of thioctic acid that has been shown in clinical studies to be neuroprotective. This study examined the effect of ALA on the symptomatology of Burning mouth syndrome (BMS). SUBJECTS AND METHODS: Forty-two patients with BMS and no clinical or laboratory evidence of organic oral disease were divided into two groups (Test and Control) each of 21 subjects, matched for age and sex. The Test group were given ALA (thioctic acid; Tiobec) for 30 days, as 600 mg per day orally for 20 days followed by 200 mg per day for 10 days. The Control group were given cellulose starch 100 mg per day as placebo for 30 days. All BMS patients were reviewed at 10-day intervals and scored for changes in symptomatology. RESULTS: Significant improvements were shown in the symptomatology of BMS in up to two-thirds of patients with BMS receiving alpha-lipoic acid, in about 15% of those using placebo and also in up to two-thirds of those who, having tried placebo, were switched to ALA.     

Analgesic effect of topical oral capsaicin gel in burning mouth syndrome

Objective: To investigate the effectiveness of repeated topical application of oral capsaicin gel in two different concentrations for relief of burning/stinging sensations in patients with burning mouth syndrome (BMS).

Material and methods: This randomized double-blind cross-over study included 22 female patients with BMS. The patients were randomized for topical application of either 0.01% or 0.025% oral capsaicin gel on the dorsal part of tongue three times daily for 14 days, followed by 14 days wash-out period, and finally treatment with the other concentration of oral gel three times daily for 14 days. A visual analogue scale (VAS) was used to assess the severity of pain five times during the intervention period.

Results: 18 patients completed the intervention. Their VAS score at baseline was 5.5?±?0.6?cm (mean?±?SD). Treatment with the two concentrations of capsaicin gels significantly improved the burning/stinging symptoms assessed on VAS compared with baseline (p?=?0.002). There was no statistically significant difference between the two concentrations of the gels on relieving symptoms. Four patients dropped out during the intervention period due to gastrointestinal side-effects.

Conclusions: Topical capsaicin might be an alternative for the short-term treatment of BMS. However, further studies are needed to investigate especially the gastro-intestinal side-effects which may limit its long-term use.     

Oral pain perception and taste in Burning Mouth Syndrome

J Oral Pathol Med (2010) 39 : 22–27
Background:  Aim of this study was to investigate the effect of idiopathic burning mouth syndrome (BMS) on both, the pain perception within trigeminal lingual nerve distribution and gustatory sensitivity using capsaicin threshold test, and regional taste tests, respectively.
Methods:  Pain thresholds for capsaicin were assessed using capsaicin-impregnated filter-paper strips. The strips were placed midline on the tongue tip for whole mouth testing with the mouth closed, and on the left or right edge of the extended anterior tongue for lateralized testing. Measures of gustatory function were obtained by validated "taste strips" test kit and electrogustometry. The tests were applied to 13 patients with BMS. Results were compared with those from 28 healthy subjects.
Results:  Patients with BMS exhibited a decreased gustatory and somatosensory perception compared with healthy controls. These changes were found for lateralized tests but not for the whole mouth test procedure. Duration of disorder showed an effect on the capsaicin threshold, with patients being less sensitive to capsaicin exhibiting an increased duration of disorder.
Conclusion:  Both pain-related and gustatory sensitivies of the tongue are found to be decreased in BMS.     

The efficacy of topical hyaluronic acid in the management of oral lichen planus

Background:  The aim of this study was to evaluate the efficacy of a topical hyaluronic acid (HA) gel preparation (0.2%) in the management of oral lichen planus (OLP).
Methods:  A total of 124 patients with erosive OLP participated in a randomized, placebo-controlled, double-blind trial to evaluate the efficacy of a topical HA preparation. Outcome measures included soreness relief following immediate application, oral function and size of erosive/ulcerative area. Patients were medicated for 28 days and completed a log diary recording oral function and soreness scores.
Results:  Application of topical HA produced a significant reduction ( P  < 0.05) in soreness scores when compared with placebo for up to 4 h post-application. There was no difference between treatment groups ( P  > 0.05) with respect to oral function. Patients treated with 0.2% HA showed a significant reduction ( P  < 0.05) in the size of the erosive/ulcerated area after 28 days of treatment when compared with baseline. There was no significant difference in changes in ulcerative areas between treatment groups.
Conclusions:  Topical HA (0.2%) does appear to be of some benefit in the management of erosive lichen planus providing efficacy for up to 4 h after administration. Very frequent applications should be considered to obtain a more significant clinical benefit. Topical HA gel may be a useful addition to the treatment option for OLP.     

Expression of phosphorylated Akt in oral carcinogenesis and its induction by nicotine and alkaline stimulation

Background:  In Taiwan, it is well documented that cigarette smoking and areca nut chewing contribute to the risk of oral squamous cell carcinoma (OSCC). The role of phosphorylated Akt (p-Akt) in oral carcinogenesis induced by nicotine and alkaline environments was investigated.
Method:  Immunohistochemistry (IHC) was used to detect p-Akt expression in cancerous ( n  = 30) precancerous ( n  = 30), and normal mucosa tissues ( n  = 10). Western blotting was used to detect time-dependent induction of p-Akt by 100 μM nicotine in normal human bronchial epithelial cell (NHBE), normal human oral keratinocytes (NHOK), immortalized human epithelial cells (HaCaT) and OEC-M1 cells, dose-dependent induction of p-Akt in OEC-M1 and HaCaT cells and pH effect of p-Akt in OEC-M1. The unpaired t -test and the Fisher's exact test were used to analyze the p-Akt immunoreactivity in various groups and its association with clinicopathological parameters.
Results:  Higher p-Akt expression in cancerous group than in normal mucosa ( P  = 0.0002) and precancerous ( P  = 0.0049) groups was observed. A time-dependent increase in p-Akt in the NHBE, NHOK, HaCaT and OEC-M1 cell lines was observed with 100 μM nicotine treatment. The dose-dependent increase in p-Akt by nicotine treatment in HaCaT and OEC-M1 cells was obviously observed. Higher p-Akt expression in more alkaline environment (pH 8.0) was observed than at pH 7.4 in OEC-M1 cells.
Conclusion:  A potential role for increased p-Akt may relate to the dose and time of nicotine use. The potential role of an alkaline environment to enhance nicotine-related oral carcinogenesis may exist.     

The close association between dental and periodontal treatments and oral ulcer course in behcet's disease: a prospective clinical study

Objective:  The aim of the study was to evaluate the influence of dental and periodontal treatments to the course of oral ulcers in patients with Behcet's disease (BD).
Methods:  Fifty-eight consecutive BD patients with oral ulcers were studied. Twenty-nine patients were in the intervention group (F/M: 15/14, mean age: 39.6 ± 6.9 years) and 29 (F/M: 15/14, 39.4 ± 10.6 years) were followed with a conventional treatment approach. In addition to oral hygiene education, dental and periodontal treatments were carried out in the intervention group, whereas the control group was only given oral hygiene education. Patients were evaluated in the pre-treatment observation period (1 month), treatment period (1 month) and 6 months after treatment.
Results:  An increase in the number of new oral ulcers (4.1 ± 3.5) was observed within 2 days during the treatment compared with 3–30 days during treatment month (2.3 ± 1.2) ( P  = 0.002). However, 6 months after the treatment, the number of oral ulcers (1.9 ± 1.5) was significantly lower compared with the pre-treatment observation (4.8 ± 3.2) ( P  = 0.000) and treatment periods (6.4 ± 2.3) in the intervention group ( P  = 0.05), whereas a similar oral ulcer presence was observed in the control group (2.8 ± 2.4, 3.7 ± 2.3 and 4.8 ± 4.3, respectively) ( P  > 0.05). Dental and periodontal indices were also better in the intervention group during the 6-month follow-up.
Conclusion:  Our results suggest that, in BD patients, dental and periodontal therapies could be associated with a flare-up of oral ulcers in the short term, but may decrease their number in longer follow-up. They also lead to a better oral health.     

Randomized trials for the treatment of burning mouth syndrome: an evidence-based review of the literature

Burning mouth syndrome (BMS) is defined as a chronic pain condition, characterized symptomatically by a generalized or localized burning sensation in the oral cavity. Various drugs have been used in attempting to treat BMS, but there is insufficient evidence to show the effect of any effective treatment. The aim of this review was to assess the effectiveness of therapies for BMS. Randomized controlled trials (RCTs) enrolling patients with a diagnosis of BMS were identified by searching Pubmed and Scoppus databases. The methodological quality of included studies was assessed on the basis of the method of allocation concealment, blindness of the study, loss of participants, size sample, and outcome concealment. A total of 12 relevant articles were analyzed. Therapies that used capsaicin, alpha-lipoic acid (ALA), and clonazepam were those that showed more reduction in symptoms of BMS. However, many studies of therapeutic interventions in BMS lack consistency in their results, because they use in their methodology, sample and a relatively short time of therapy and often do not provide a follow-up of patients treated. Thus, future studies are required to establish the treatment for patients suffering from this chronic and painful syndrome.     

Burning mouth syndrome: the role of contact hypersensitivity

Background:  Burning mouth syndrome is a burning sensation or stinging disorder affecting the oral mucosa in the absence of any clinical signs or mucosal lesions. Some studies have suggested that burning mouth syndrome could be caused by the metals used in dental prostheses, as well as by acrylate monomers, additives and flavouring agents, although others have not found any aetiologic role for hypersensitivity to dental materials.
Objective:  To evaluate the extent and severity of adverse reactions to dental materials in a group of patients with burning mouth syndrome, and investigate the possible role of contact allergy in its pathogenesis.
Materials and methods:  We prospectively studied 124 consecutive patients with burning mouth syndrome (108 males; mean age 57 years, range 41–83), all of whom underwent allergen patch testing between 2004 and 2007.
Results:  Sixteen patients (13%) showed positive patch test reactions and were classified as having burning mouth syndrome type 3 or secondary burning mouth syndrome (Lamey's and Scala's classifications).
Conclusion:  Although we did not find any significant association between the patients and positive patch test reactions, it would be advisable to include hypersensitivity to dental components when evaluating patients experiencing intermittent oral burning without any clinical signs.     

Idiopathic dysgeusia; an open trial of alpha lipoic acid (ALA) therapy

We selected two homogenous groups, each of 22 patients with idiopathic dysgeusia, an altered perception of taste, matched for age and sex, for an open trial of alpha lipoic acid compared with placebo. The 22 patients in the study group were treated with alpha lipoic acid for 2 months. The 22 patients in the control group were treated for 2 months with carboxymethylcellulose. The latter group was then treated with alpha lipoic acid for 2 months. The results showed significant symptomatic improvements compared with placebo, in both groups of patients with dysgeusia treated with alpha lipoic acid, suggesting that idiopathic dysgeusia may be a neuropathy comparable to the burning mouth syndrome.     

Oxidant/antioxidant status in recurrent aphthous stomatitis

Objective:  Recurrent aphthous stomatitis (RAS) is a common oral mucosal disorder characterized by recurrent, painful oral aphthae, and oxidative stress presumably contributes to its pathogenesis. The study was performed to evaluate the involvement of oxidant toxicity in this disorder.
Methods:  Patients with RAS ( n  = 26) and age- and sex-matched healthy control subjects ( n  = 20) were included in this study. Following an overnight fast, blood specimens were obtained. Plasma malondialdehyde concentrations and erythrocytes glutathione peroxidase activities were determined. Also, plasma vitamin E and selenium levels were detected. Mann–Whitney U -test was performed for statistical evaluation.
Results:  Oxidative stress was confirmed by the significant elevation in plasma malondialdehyde levels and by the significant decrease in glutathione peroxidase activities, vitamin E and selenium levels ( P  < 0.001).
Conclusions:  Our results indicated that lipid peroxidation and the inadequacy of the defense system seem to play a crucial role in the pathogenesis of recurrent aphthous stomatitis.