Efficacy of alpha-lipoic acid in patients with burning mouth syndrome compared to that of placebo or other interventions: a systematic review with meta-analyses

Abstract

Burning mouth syndrome (BMS) is a chronic oral disorder of unknown etiology which presents therapeutic challenges. Alpha-lipoic acid (ALA) has been studied as a potential treatment for BMS. The objective of this systematic review and meta-analysis was to evaluate the effectiveness of ALA compared to that of placebo or other interventions in individuals with BMS. Randomized controlled trials (RCT) using ALA to treat BMS were identified from MEDLINE, Cochrane Library, EMBASE, and Web of Science up to February 3, 2021. The assessment of the risk of bias in the included studies was based on the Cochrane guidelines. The primary outcome evaluated was the visual analog scale (VAS) pain intensity. ALA was compared with placebo, clonazepam, gabapentin, pregabalin, ALA plus gabapentin, capsaicin, Biotène^®, and laser therapy. Altogether, 137 records were scanned for inclusion/exclusion, and nine RCTs (two unclear and seven at high risk of bias) were included in the qualitative and quantitative analyses, with a total of 594 patients with BMS included in this review. All studies reported an improvement in VAS pain scores ranging from -0.72 to -2.77. Meta-analysis results showed a non-significant reduction in pain intensity for ALA (P = 0.616) compared to that of placebo on a VAS of 0-10. Patients taking ALA were 1.923 times more likely to show an improvement in self-reported BMS symptoms (P = 0.031) than those in the placebo group. Clonazepam and pregabalin showed a significant VAS pain reduction of 4.08 and 4.68 (P < 0.001), respectively, compared to that with ALA. Although ALA intervention provided a non-significant improvement in the pain score and was more likely to produce a reduction in BMS symptoms, the evidence was of low quality. Further research is needed to establish clear guidelines for the use of ALA for BMS treatment.

Keywords: Alpha-lipoic acid; Burning Mouth Syndrome; Clonazepam; Meta-Analysis; Systematic Review.

Fig. 1. PRISMA 2020 flow diagram with included searches of databases and other sources [18]. Abbreviations: ALA, alpha-lipoic acid; BMS, burning mouth syndrome; n, number; RCT, randomized controlled trial.

Fig. 2. Summary of risk of bias of eligible. RCT, randomized controlled trial.

Fig. 3. Pre- and post-VAS pain intensity reported in ALA groups (A), placebo groups (B), and other active interventions (C). Abbreviations: ALA, alpha-lipoic acid; Post-Tx, post-treatment; VAS, visual analog scale.

Fig. 4. Meta-analyses and subgroup analyses. (A) Change in pain intensity from baseline (VAS 0-10) with ALA compared to that with placebo. (B) Change in pain intensity from baseline (VAS 0-10) with ALA compared to that with other active interventions. (C) Risk of any improvement in BMS with ALA versus placebo groups. (D) Risk of any improvement in BMS with ALA versus other active interventions. Abbreviations: ALA, alpha-lipoic acid; CI, confidence interval; VAS, visual analog scale.