Summary of findings 5. Dietary supplements versus placebo for treating people with burning mouth syndrome.

Dietary supplements compared with placebo for treating burning mouth syndrome
Patient or population: people diagnosed with burning mouth syndrome Settings: secondary care Intervention: dietary supplements (ALA with (+ vitamins, + lycopene + green tea extract) or without adjunctive active ingredients; hypericum perforatum (St John's Wort); 'Catuama' herbal compound; lycopene) Comparison: placebo
Outcomes	Anticipated absolute effects* (95% CI)		Relative effect (95% CI)	Number of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Placebo	Dietary supplements
Symptom relief: short‐term (≤ 3 months)	There is insufficient or contradictory evidence regarding the benefit of any of the evaluated dietary supplements over placebo to evaluate short‐term symptom relief			628 (12 RCTs)	⊕⊝⊝⊝ very low1	Interventions evaluated for short‐term symptom relief included: ALA without adjunctive active ingredients (3 RCTs) ALA with vitamins (5 RCTs) ALA with lycopene and green tea extract (2 RCTs) hypericum perforatum (St John's Wort) (1 RCT) 'Catuama' herbal compound (1 RCT) lycopene (1 RCT) The mean VAS pain score (scale 0‐10: lower better) for long‐term symptom relief (> 3 to ≤ 6 months) was 0.89 lower (2.37 lower to 0.59 higher) for people treated with ALA (with or without adjunctive vitamins) than the placebo group (2 RCTs, 94 participants)
Change in quality of life (QoL): short‐term (≤ 3 months) ‐ Mean OHIP‐14 score (Scale 0‐70: lower better)	17.38	0.93 higher (3.14 lower to 5.00 higher)	‐	50 (1 RCT)	⊕⊝⊝⊝ very low2	Single study assessing short‐term QoL, anxiety and depression compared lycopene with placebo No data were available to estimate long‐term change in QoL, or its surrogate markers: anxiety or depression No data were available to estimate the effect of other dietary supplements; however, 1 study (43 patients), comparing hypericum perforatum extract with placebo, evaluated QoL from patient self‐reports and narratively indicated that both intervention and placebo participants were better able to cope at trial completion
Change in QoL ‐ anxiety: short‐term (≤ 3 months) ‐ Mean HAD anxiety score (Scale 0‐21: lower better)	11.5	2.85 lower (5.28 to 0.42 lower)			⊕⊝⊝⊝ very low3
Change in QoL ‐ depression: short‐term (≤ 3 months) ‐ Mean HAD depression score (Scale 0‐21: lower better)	6.25	1.87 lower (4.23 lower to 0.49 higher)			⊕⊝⊝⊝ very low4
Change in taste	No included studies reported change in taste
Change in feeling of dryness	No included studies reported change in feeling of dryness
Adverse effects	For people treated with ALA (with or without adjunctive active ingredients), there was evidence of an increase in headache occurrence (RR 10.87, 95% CI 1.36 to 87.03; 2 RCTs, 118 participants) or gastrointestinal complaints (RR 4.00, 95% CI 1.21 to 13.27; 3 RCTs, 138 participants). There was no difference in blood pressure (1 RCT, 38 participants) or intermittent facial skin rash (1 RCT, 80 participants) For people treated with ALA (with or without adjunctive active ingredients) or 'Catuama' herbal compound, there was no difference in drowsiness (2 RCTs, 110 participants) For people treated with 'Catuama' herbal compound (1 RCT, 72 participants), there was no difference in exacerbation of symptoms, insomnia or weight gain 1 RCT (60 participants, ALA with adjunctive vitamins) reported no "notable adverse effects", and another RCT (40 participants, ALA with adjunctive vitamins) narratively reported 4 intervention participants (20%) experienced heartburn, before correction by administration of ranitidine (150 mg) Severe headache resulting from hypericum perforatum extract use caused 1 participant (5%) to discontinue treatment (1 RCT, 43 participants) 4 RCTs (224 participants, ALA (with or without adjunctive active ingredients) and lycopene) narratively reported that no adverse effects occurred				⊕⊝⊝⊝ very low5
*The basis for the assumed risk is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI) ALA: alpha lipoic acid; CI: confidence interval; HAD: Hospital Anxiety and Depression scale; OHIP‐14: Oral Health Impact Profile‐14; OIS: optimal information size; RCT: randomised controlled trial; RR: risk ratio; VAS: visual analogue scale
GRADE Working Group grades of evidence High quality: further research is very unlikely to change our confidence in the estimate of effect Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate Very low quality: we are very uncertain about the estimate

¹Downgraded twice due to high risk of bias across multiple domains; downgraded twice due to inconsistency between, and within, subgroups; 1 RCT (Carbone 2009) contributes to 2 subgroups: ALA with vitamins and ALA without adjunctive active ingredients.
 ²Assumed placebo risk based on mean placebo group QoL score at short‐term (≤ 3 months) follow‐up; downgraded once due to high risk of bias relating to selective reporting and lack of baseline data; downgraded once due to indirectness: concerns relating to applicability, only 1 type of dietary supplement assessed, effects of other dietary supplements may differ; downgraded twice due to imprecision: OIS not met, and 95% CI includes no effect.
 ³Assumed placebo risk based on mean placebo group anxiety score at short‐term (≤ 3 months) follow‐up; downgraded once due to high risk of bias relating to selective reporting and lack of baseline data; downgraded twice due to indirectness: use of surrogate measure, and also concerns relating to applicability, only 1 type of dietary supplement assessed, effects of other dietary supplements may differ; downgraded once due to imprecision: OIS not met.
 ⁴Assumed placebo risk based on mean placebo group depression score at short‐term (≤ 3 months) follow‐up; downgraded once due to high risk of bias relating to selective reporting and lack of baseline data; downgraded twice due to indirectness: use of surrogate measure, and also concerns relating to applicability, only 1 type of dietary supplement assessed, effects of other dietary supplements may differ; downgraded once due to imprecision: OIS not met.
 ⁵Downgraded twice due to high risk of bias across multiple domains; downgraded twice due to inconsistency between, and within, subgroups; downgraded once for imprecision: wide CIs estimated around effect sizes.