Carbone 2009.

Methods	Single centre, placebo‐controlled parallel RCT
Participants	66 BMS patients Sex: 54 F:12 M (F 82%:M 18%) Of the 52 patients who completed the trial, mean age was reported as 67.3 years (SD 11.9) Inclusion/exclusion and diagnostic criteria appropriate
Interventions	Intervention category: dietary supplements Group 1: (n = 22) 400 mg alpha lipoic acid (ALA) and vitamins B (1, 2, 6, 12), C, E, and folic acid (vitamin B9) ‐ 1 pill twice/day by mouth 30 minutes after food for 8 weeks followed by phase II which was a 2‐month follow‐up period without therapy (Tiobec, produced by Laborest) Group 2: (n = 22) 400 mg alpha lipoic acid ‐ 1 pill twice/day by mouth 30 minutes after food for 8 weeks followed by phase II which was a 2‐month follow‐up period without therapy (produced by Laborest as standalone ALA specifically for this trial) Group 3: (n = 22) placebo pill 1 pill twice/day 30 minutes after food (containing dicalcium phosphate, microcrystalline cellulose, hydroxipropylmethyl cellulose, silicon dioxide, vegetal magnesium stearate, shellac and stearic acid) for 8 weeks. Followed by phase II which was a further 2‐month follow‐up period without 'therapy'
Outcomes	Proportion of participants achieving a 50% improvement in BMS symptoms from baseline to T3 and T4, measured by the VAS score. Each participant was examined by the same examiner (blinded to treatment) at the beginning of therapy (T0), 2 weeks (T1) and 4 weeks (T2) after the start of treatment, at the end of treatment (T3), and after 2 months of follow‐up (T4) Quality of pain experienced by participants was also assessed using the McGill Pain Questionaire. Similarly, each participant was examined by the same examiner (blinded to treatment) at the beginning of therapy (T0), at 2 weeks (T1) and at 4 weeks (T2) after the start of treatment, at the end of treatment (T3), and after 2 months of follow‐up (T4)
Source of funding	Not reported
Notes	The study authors query whether all participants should have been treated with a 7‐day course of antifungal therapy to eradicate subclinical candidosis. Current clinical practice would consider this unnecessary and irrelevant if the diagnosis is BMS. Is 8 weeks treatment sufficient time to provide a definitive answer? SES: not reported Conflict of interests: not reported Data analysis: per‐protocol
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quotation: "Randomization was performed using computer‐generated random number tables in order to assign patients to receive one of the three 8‐week standardized treatments" Comment: satisfactory
Allocation concealment (selection bias)	Unclear risk	Comment: allocation concealment was not discussed
Blinding (performance bias and detection bias) Blinding of participants	Low risk	Quotations: "Double blind"; "The medication (pills) was distributed in identical containers. During treatment, neither the physician nor the patients knew which of the three medications they were using" Comment: satisfactory
Blinding (performance bias and detection bias) Blinding of outcome assessors	Low risk	Quotation: "Each patient was examined by the same examiner (blind to treatment)" Comment: satisfactory – patient‐reported outcomes only
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Quotation: "Fourteen patients did not complete the study and were excluded from the efficacy sample. No side effects were reported as being a reason for withdrawal from the trial: 10 patients dropped out because of lack of compliance, and four patients because of lack of efficacy. No significant difference in the rate of dropout was observed among the three groups (p = 0.079, v2‐test)" Intention‐to‐treat was also considered Comment: reasons for dropouts were described overall, but not for each arm. 10 participants "dropped out" due to a "lack of compliance" – it is unclear exactly what "lack of compliance" meant and how these 10 were spread across each of the study arms
Selective reporting (reporting bias)	Unclear risk	Comment: full McGill Pain Questionnaire data not provided but alluded to and partially described Quotation: "The McGill Pain Questionnaire scores showed some improvements compared to the baseline measurements (Friedman test), but significant differences among the three groups were never observed (Kruskall–Wallis test). In particular, the affective, and the mixed affective/evaluative subscales slightly improved in Group C (Friedman test: p = 0.004 and 0.022, respectively); conversely, the evaluative subscale improved in all three groups (Friedman test: Group A, p = 0.007; Group B, p = 0.003; Group C, p = 0.046)" Comment: no baseline characteristic data were presented (only P values of statistical tests), full McGill Pain Questionnaire data not provided (again only P values)
Other bias	Low risk	Comment: no other obvious risks of bias