Table 2.

Tabular description of all the selected eligible of vivo RCTs human studies, summarising the demography, study design, symptoms, diagnostic criteria, functional problems, affected areas, intervention groups, methods of assessment, evaluation period and outcomes. Abbreviation: RCTs: randomized controlled trials, SB: Single-blind; DB: double-blind; ADH: anxiety and depression scale, OHIP-14: oral health impact profile; VNS: visual numeric scale; VAS: visual analogue scale; PPI: present pain intensity scale; NRS: numerical rating scale; HADS, hospital anxiety–depression scale; PGI-I, patient global impression of improvement; ELISA: enzyme-linked immunosorbent assay; GDS: geriatric depression scale; BMS: burning mouth syndrome; SOB: secondary oral burning; TNF-α: transforming necrotic factor-alpha; L: lip; TT: tip tongue; LT: lateral tongue; DT: dorsal tongue; BM: buccal mucosa; LM: labial mucosa; HP: hard palate; SP: soft palate; G: gingivae; AM: alveolar mucosa; VM: vestibular mucosa; SM: sublingual mucosa; UL: upper lip; LL: lower lip; LG: lower gingivae;: MR: mandibular ridge; QoL: quality of life; 1/12: 1 month; 2/12: 2 months; 3/12: 3 months; 4/12: 4 months; 6/12: 6 months; QoL-OH: QoL related to oral health; vs: versus; OHIP-CRO 14: Croatia version of OHIP-14; 3/52: three weeks; 8/52: 8 weeks; 12/52: twelfth weeks: 12/52; COB: capillary oral bed; 14/7: 14 days; μ: micron; yrs: years; UWS: unstimulated whole salivary flow; SD: standard deviation; MPQ: McGill Pain Questionnaire; vs: versus; SF-36: Short Form 36 Health Survey Questionnaire; SCL 90-R: Symptom Checklist-90-R; COB; infrared: IR; near-infrared: NIR. List of the abbreviations are listed in Supplementary File S2.

Study, Year, Origin and Citation	Journal Name/ Impact Factor (IF)	Study Design	Presented Symptoms and Duration	Diagnosis	Affected Area (s)	Functionality Problem (s)	Sample Size (n)	Gender Male (M), Female (F)	Age (yrs) (Mean ± SD)	Intervention Groups and Subject, No. Allocation	Evaluation Period	Assessed Parameter (s)	Evaluation Methods	Outcome and Conclusion
Bardellini et al., 2019 (Italy) [74]	Med Oral Patol Oral Cir Bucal (IF: 1.71)	RCT/DB	Pain Burning sensation, 6/12	IASP- 2016	TT, LT, DT, UL, LL, BM	Functional limitation, physical pain, psychological and social disabilities	85 (F)	F: 42 (G1) F: 43 (G2)	G1: 59 ± 9.51 G2: 60.86 ± 10.02	G1 (LLLT): 43 G2 (Placebo): 42	At baseline, mid-treatment (5th Session), End-treatment, 1/12 after treatment	Pain, Functionality limitation, Stress/ anxiety, Physical activity,	VAS Italian- OHIP	On VAS: in G1, a significant reduction in pain (p = 0.0008) and improvement in QoL-OH (p = 0.0002). VAS: at 5th session, a reduction in pain but no statistically significant differences between G1 and G2 (p = 0.6232). At end-treatment: statistically significant reduction in symptoms in G1 (p = 0.0008) and kept at 1/12 follow-up (p = 0.0005). On OHIP: G1 9.00 ± 4.20 vs. G2 −4.87 ± 3.75
Valenzuela et al., 2017 (Spain) [75]	J Oral Rehabil (IF: 2.4)	RCT/ Prospective/partially blinded/single centre	Oral burning/Pain, ≥6/12	IHS-2013	NI	Pain, Oral burning sensation. Reduction in saliva flow	44	M: 3 F: 41	65.5	G1 (LLLT): 16 (4 J) G2 (LLLT): 16 (6 J) G3 placebo/ sham laser: 12	At baseline, 2/52 and 4/52	Pain, oral health, salivary flow, anxiety/ depression, over all treatment satisfaction	VAS, OHIP-14 (Spanish version), Sialometry HADS, PGI-I	VAS and OHIP-14 scores reduced significantly over time of treatment in all groups. At 2/52 and 4/52: VAS and OHIP-14 for G1 and G2 significantly lower than in G3. No significant differences between G1 and G2. Xerostomia severity and HAD: no significant differences between groups. PGI-I: no significant differences G1 and G2. Overall VAS scores improvement from baseline to end-LLLT were: G1: 15.7%, G2: 15.6%, G3: 7.3%
Arbabi-Kalati et al., 2015 [76]	J Clin Exp Dent. (IF: 1.73)	RCT/SB	Pain, burning sensation, 4/12	IASP- 2016	10 areas of oral mucosa BM, T, FM, SP, HP	Taste disturbance Pain intensity	20	M: 0 F: 20	G1: 47.2 G2: 46.6	G1 (LLLT): 10 G2 (Placebo Sham): 10	At baseline and after treatment Follow-up: NI	Pain, QoL	VAS, Persian- OHIP	Statistically significant improvement in burning sensation in G1 (p = 0.004), compared to G2. QoL: statistically significant in G1 (p = 0.01). VAS: G1: −4.4 ± 3.0 G2: −0.2 ± 1.5. OHIP: G1: −15.0 ± 11.4 vs. G2: 0.3 ± 11.5
Arduino et al., 2016 (Italy) [77]	Lasers Med. Sci. (IF: 1.94)	RCT/comparative Double or single blind: NI,	Pain, burning sensation 6/12	IASP- 2016	Oral mucosa	Functional limitation, physical pain, psychological and social disabilities	33 Caucasian	M: 8 F: 25	G1: 68.5 G2: 65.4	G1 (LLLT): 18 G2 [Clonazepam (2 mg) lozenge]: 15	At 3/52, 8/52 and 12/52	Pain, QoL, PH saliva, anxiety/ depression	VAS, MPQ, PPI, OHIP-14, HADS, GDS, UWS pH	G1 was superior to G2, in improving pain intensity in all parameters but statistically significant only at 8/52 (p = 0.026) VAS: G1: −2.78 ± 4.08 vs. G2: −1.15 ± 1.80. MPQ: G1: −10.05 ± 4.80 vs. G2: −11.00 ± 4.80. OHIP: G1: −11.06 ± 32.10 vs. G2: 4.40 ± 43.00. No adverse effects in G1 but 32% of dizziness, fever, headache and lack apatite in G2
Sugaya et al., 2016 (Brazil) [78]	Braz Oral Res. (IF: 1.6)	RCT/SB	Burning sensation, dysgeusia, Duration: NI	IASP- 2013	Tongue, UL, LL, BM, MR SP; HP, LG	Xerostomia & dysgeusia	30 allocated Analysed only 23	M: 2 F: 21 (7 lost to follow-up)	59.7 (29–87)	Allocated: LG (LLLT): 15 CG (Placebo): 15, but analysed: LG: 13 CG: 10	At baseline, 15 mins after irradiation, At 14/7 1/12, 2/12 and 3/12	Pain	VAS, global perception chart pain index	A significant improvement of symptoms in LG over CG in two measurements only. Positive effect in emotional profile in LG and CG. CR: LG 6/13 vs. CG 4/10
Spanemberg et al., 2015 (Spain) [79]	J Biomed Opt. (IF: 3.17)	RCT/DB	Burning sensation, Pain, 6/12	IASP- 2016	TT, DT, LT (bilateral), UL, LL, HP, SP	NI	78	M: 11 F: 67	G1: 63.6 ± 9.61 G2: 60.5 ± 6.42 G3: 63.2 ± 6.91 G4: 61.5 ± 8.76	Three groups of LLLT vs. placebo G1: [LLLT IR (IR1W) ]: 20 G2: [LLLT-IR (IR3W)]: 20 G3: (LLLT red: 19. G4 (Placebo, Sham): 19	Baseline, end-treatment & 8/52 after treatment	Pain, QoL	VAS, VNS, OHIP-14	Significant improvement in symptoms and QoL (p < 0.01) in G1 compared to G4. On VS and VNS: G1 and G2 differed significantly compared to G4, but no significant difference between G3 and G4. OHIP-14: significant difference between G2 and G4. G1 and G3 didn’t differ significantly to G4
Skrinjar et al., 2020 (Croatia) [80]	Act Stomatol Croat. (IF: 0.75)	RCT/DB	Burning sensation, ≥3 months	IASP- 2016	Both sites: tongue, lip or HP	Xerostomia, intraoral disability	23	M: 3 F: 20	LLLT: 61 Placebo: 62	G1 (LLLT): 12 G2 (Placebo): 11	At baseline, end-treatment	Burning sensation, Salivary cortisol level	VAS, Unstimulated saliva (ELISA)	VAS scores and salivary cortisol levels were significantly lower in G1 and G2. LLLT was not better than placebo. No adverse effects reported for both groups
Pezelj-Ribarić et al., 2013 (Croatia) [81]	Lasers Med Sci. (IF: 1.94)	RCT/ unspecified	Burning sensation, pain Duration un-specified	IASP-2013	NI	NI	40	M: 13 F: 27	G1: 60.2 G2: 61.1	G1 (LLLT): 12 G2 (Placebo): 9	NI	Pain, UWS	VAS, TNF-α & IL-6 levels	On VAS: no significant differences in pain reduction between G1 and G2. In G1: no reduction of symptoms. VAS scores: G1: −4.2 vs. G2: −3. Decrease in TNF-α and IL-6
Sikora et al., 2018 (Croatia) [82]	Acta Clin Croat. (IF: 0.53)	RCT/SB	Burning mouth symptoms duration: NI	IASP-2016	NI	NI	44	M: 1 F: 43	Range 56–83 Mean age: 67.56	LLLT and Placebo but no data available	At baseline and after each treatment session	Pain, QoL	VAS, OHIP-CRO- 14	OHIP-CRO14: No significant differences between the groups prior and after LLLT (p > 0.05%). Neither of therapy protocols improved QoL scores. VAS score: significant decreases in both groups (p < 0.05%) and (p < 0.01%).
Spanemberg et al., 2019 (Spain) [83]	J Oral Medicine and Pathology (IF: 2.5)	RCT/DB	Pain/ burning, anxiety/ depression, 3/12	ICHD -2013	TT, LT, DT, BM, LM, HP, SP; G, AM	Intraoral & psychological disabilities	21	M: 1 F: 20	LG: 66.3 ± 7.52 CG: 66.4 ± 6.31	LG: 12 CG (sham): 9	At baseline, 8th session, 2/12 after treatment	Pain/ burning, dry mouth, dysphagia	VAS, HANDS	Initial VAS score mean was 8.9 in LG and 8.3 in CG (p > 0.05%). At end-treatment, VAS score was 5.5 in LG and 5.8 in CG. At 2/12, VAS score was 4.7 in LG and 5.1 in CG. Marginal significant improvement in dry mouth and dysphagia (p = 0.0538)
De Pedro et al., 2020 (Spain) [84]	Oral Diseases (IF: 2.6)	RCT/SB	Pain/burning, depression/ anxiety, lack of sleep >3/12	ICHD-3-2018	VM, L, BM, HP, LT, DT, SM	Intraoral disability, mental & psychological disabilities, lack of sleep	20	M: 2 for each group F: 8 for each group	LG: 66.30 ± 15.19 CG = 67.60 ± 10.68	LG: 10 CG (sham): 10	At baseline, 10th session 1/12 and 4/12 after treatment	Pain, sleepiness QoL, anxiety/ depression	VAS, SF-36, Psychometric SCL 90-R, MPQ, OHIP-14	On VAS: LG showed an improvement in pain at end-treatment and increased at 1/12 follow-up and continued to improve at 4/12 in (90%) (p = 0.013). In GC, 20% improvement at end-treatment and worsened in 40% at 1/12 and kept worsening in 40% at 4/12 follow-up. On McGill and OHIP-14: scores decreased in LG at end-treatment and maintaiend over the follow-up period, indicating a positive impact on psychological state. On mental health score: significant decrease in anxiety in LG at end treatment and at 4/12 follow-up. Statistical significant improvement in SF-36 scores in LG at 1/12 follow-up.
Scardina et al., 2020 (Italy) [85]	Dent J (Basel) (IF: NI)	RCT/DB	IO pain and burning sensation, >3/12	Unspecified criteria but specified burning sensation without specifying symptoms’ duration	ULM, DT, BM, LLM	Pain	40	Only F	62.06 ± 3.1	G1: LLLT: 20 G2: Placebo: 20	At baseline, after each treatment session (8 sessions) and 60 days after treatment	Pain, Capillary bed: Length, diameter, density, morphology tortuosity	VAS, NRS, Video-capillaroscopy evaluation	G1: a lasting improvement in symptoms. No statistical significant difference in COB in G2 (p > 0.05). Reduction in diameter of the following areas in G1: BM: 3μ, LL: 3μ, DT: 2μ. An increase in capillary length in all irradiated areas (p < 0.05). PBMT induced reduction in capillary diameter (long time period), reflected an improvement in clinical profile.