Femiano 2002b.

Methods	Single centre, placebo‐controlled parallel RCT
Participants	80 BMS patients Median age 63 years (range 30 to 74) Sex: 48 F:32 M (F 60%:M 40%)
Interventions	Intervention category: dietary supplements + topical treatments + cholinergics Group 1: (n = 20) bethanechol (urecholine) 5 mg oral dose every 8 hours between meals Group 2: (n = 20) lactoperoxidase oral solution (Biotene oral rinse) topically 5‐6 times daily Group 3: (n = 20) alpha lipoic acid and vitamins B (1, 2, 6, 12), C, E, and folic acid (vitamin B9) in 200 mg oral pills, 3 times a day (every 8 hours) for 60 days (Tiobec, produced by Laborest) Group 4: (n = 20)placebo ‐ xylitol 3% in distilled water (no further details provided) Study conducted over 60 days
Outcomes	Bespoke BMS symptomology change scale scored as: Worsening, Unchanged, Slight improvement, Decided improvement, Resolution – unclear as to how this was assessed Weekly "assessments" performed – further details not provided. Unclear whether symptomatology or side effects were assessed at every visit
Source of funding	Not reported
Notes	16/80 participants reported to have "used anxiolytic drugs to control the BMS" – these were allocated equally amongst the study arms 2 participants were reported in results section to be ongoing with anxiolytics during trial Unusually high number of male participants included within the study cohort It is unclear whether other ALA studies published by the author around the same time used the same participants or not SES: not reported Conflict of interests: not reported Data analysis: ITT
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quotations: "This BMS cohort was then randomly divided into 4 groups"; "matched for age and sex" Comment: no detail provided about how randomisation was conducted
Allocation concealment (selection bias)	High risk	Comment: no detail given regarding allocation concealment
Blinding (performance bias and detection bias) Blinding of participants	High risk	Quotation: "This open controlled study of α‐lipoic acid" Comment: the study is described as open‐label
Blinding (performance bias and detection bias) Blinding of outcome assessors	High risk	Quotation: "This open controlled study of α‐lipoic acid" Comment: the study is described as open‐label
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quotation: no dropouts reported. No missing data reported
Selective reporting (reporting bias)	High risk	Comment: no data provided for BMS symptoms during trial (e.g. at week 4) only after trial completion scores were given. "All patients reported increased salivation" was reported in Group 1 ‐ but this was not a prespecified outcome
Other bias	High risk	Commnent: no baseline data presented; given lack of detail regarding randomisation process substantial inequalities at baseline cannot be ruled out