Introduction
Light-based therapies, including low–level light therapy (LLLT), photobiomodulation (PBM), and light-emitting diodes (LEDs), have attracted increasing attention as noninvasive approaches to modulate biological processes [1]. Light therapy is a light–dependent treatment modality for various diseases. By delivering specific wavelengths and energy doses, light therapy is proposed to modulate cellular metabolism, enhance tissue repair, reduce inflammation, and influence neural and immune functions [2].
These mechanisms underlie its wide range of clinical applications, spanning dentistry, dermatology, oncology, musculoskeletal medicine, and neurological or psychiatric disorders [3–7].
In particular, LLLT, which is typically delivered in the red to near–infrared spectrum, is widely used in medical practice for treating various diseases. LLLT uses low–power light from lasers or LEDs, typically at wavelengths of 600 to 1,100 nm in the red to near–infrared spectrum [8]. These wavelengths are intended to elicit photobiomodulatory responses and promote positive therapeutic responses [1, 9].
Previous studies indicate that LLLT is implemented to target tissues using specific wavelengths and optimized fluence (energy density) parameters to achieve therapeutic outcomes without inducing adverse effects [10]. The energy levels applied are sufficiently low to avoid thermal effects [7]. The noninvasive nature of LLLT has contributed to its clinical appeal, although its safety profile remains incompletely characterized because adverse events have not been consistently assessed or reported.
Consequently, clinical interest has expanded globally, and numerous trials and systematic reviews have been published [11, 12].
However, despite the growing body of evidence, findings remain heterogeneous and occasionally contradictory. While some reviews report robust benefits of LLLT, others find equivocal or neutral effects [1, 10]. The diversity of light therapy parameters, including wavelength, energy density, treatment duration, and frequency, further complicates the interpretation and generalizability of the results [11].
Given this fragmented landscape, an umbrella review of systematic reviews may provide an opportunity to evaluate the breadth and credibility of the evidence [12]. This method allows for synthesis across diverse health conditions, assessment of the methodological rigor of existing systematic reviews, and identification of gaps in the literature on LLLT.
The objective of this umbrella review was to synthesize evidence from systematic reviews and meta-analyses on LLLT across clinical conditions, with a focus on effectiveness, adverse events, and methodological quality of the included reviews.
Methods
Protocol and reporting
This umbrella review followed the PRIOR statement for reporting overviews of reviews [13] and PRISMA statement for reporting systematic reviews [14]. The protocol was developed prospectively, with eligibility criteria, search methods, and data extraction procedures defined in advance, and was registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD420261327092).
Eligibility criteria
The following PICO framework and eligibility criteria were applied for this review:
Population: Human participants of any age, sex, or clinical condition were included.
Intervention: Non-thermal, low-intensity light-based therapies intended to induce photobiomodulatory effects, including low-level light therapy (LLLT), photobiomodulation (PBM), and light-emitting diode (LED) therapy, were eligible. Eligibility was determined based on intervention classification and therapeutic intent reported in the original reviews rather than predefined thresholds for wavelength, power output, or fluence because treatment parameters varied across indications and reporting was inconsistent. High-intensity light therapy, photodynamic therapy, cosmetic laser procedures, and diagnostic applications were excluded.
In reviews containing both eligible and potentially ineligible interventions, eligibility was reassessed at the primary study level. Separable primary studies using thermal or ablative laser applications, including CO₂, Er: YAG, Er, Cr: YSGG, or high-energy Nd: YAG lasers, were excluded unless their use as non-thermal photobiomodulation could be clearly established.
Comparator: Eligible comparators included sham, placebo, standard care, and active interventions.
Outcomes: Primary outcomes included pain reduction, healing or disease severity, functional improvement, and structural or biological outcomes. Because meta-analytic effect estimates were not comparable across reviews, no umbrella-level quantitative effect estimate was calculated. Secondary outcomes included adverse events, side effects, and other harms associated with the intervention.
Whether adverse events were reported and, when available, their types were summarized descriptively.
Inclusion criteria: Published systematic reviews (SRs) or meta–analyses of randomized or non–randomized controlled trials of light therapy in humans.
Exclusion criteria: Narrative or scoping reviews, non–systematic evidence syntheses, preclinical–only studies, or articles not available in English. Reviews that did not use a Cochrane risk-of-bias tool to assess the included primary studies were also excluded.
Search strategy
A systematic search was conducted in PubMed, Embase, Cochrane Library, and Web of Science databases from inception to February 24, 2026. The strategy combined database-specific subject headings and free-text terms related to phototherapy, light therapy, LLLT, and photobiomodulation, with terms for systematic reviews and meta-analyses applied where appropriate. The complete database-specific search strategies are provided in Supplementary Material 1.
Reference lists of included reviews and related citations were manually searched for additional eligible studies.
Study selection
Two reviewers independently screened the titles, abstracts, and full texts according to the eligibility criteria for study selection. Disagreements were resolved by discussion or consultation with a third reviewer if necessary.
Data extraction
Two reviewers independently extracted the data using a standardized data extraction form. The following review–level information was extracted and tabulated:
Bibliographic details (first author, year, country) of the review.Clinical conditions and categories (oral and dental conditions, musculoskeletal disorders, oncology-related complications, wound and lymphatic conditions, ocular conditions, dermatologic and hair conditions, respiratory conditions, auditory conditions).Number of included primary studies and reported sample size.Type of intervention (device type).Treatment characteristics (wavelength range, energy per point, fluence range, emission mode).Overall direction of review conclusions (favorable, neutral/mixed, or unclear).Adverse events or side effects related to the intervention.Primary outcome(s) reported in each included review.Identifiers of included primary studies for construction of the citation matrix and overlap assessment.
Where an included systematic review contained both eligible and ineligible primary studies, eligibility and extracted data were reassessed at the primary-study level. Only eligible primary studies contributed to the evidence counts, intervention characteristics, reported sample size, and overlap assessment. Reported sample size was extracted for eligible primary studies where separable and was summed descriptively across reviews.
Because some reviews reported teeth or other units of analysis and some primary studies appeared in multiple reviews, the cumulative reported sample size was not interpreted as the number of unique participants.
Adverse-event reporting was classified into three mutually exclusive categories: one or more adverse events or side effects reported, no adverse events explicitly reported, or adverse-event information not reported. The absence of reported information was not interpreted as evidence that no adverse events occurred.
Quality assessment
The methodological quality of included reviews was appraised using AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews) [15], which evaluates 16 items including protocol registration, search comprehensiveness, risk of bias assessment, and synthesis methods. Reviews were categorized as having high, moderate, low, or critically low confidence in their results, following the AMSTAR 2 guidance.
Data synthesis
The conclusions were synthesized narratively according to clinical categories. When multiple reviews addressed the same condition, their conclusions were descriptively compared. To descriptively map the direction of conclusions across the included reviews, we categorized the review authors’ overall conclusions regarding treatment effects as favorable, neutral, or unclear.
A favorable classification indicated that the review authors concluded that the intervention was beneficial; neutral indicated that the authors reported no clear benefit or mixed conclusions; and unclear indicated that no clear overall conclusion could be determined. This classification was based on the review authors’ stated interpretations and was used solely to characterize the conclusions reported in the review literature. It was not considered a quantitative synthesis of efficacy, effect magnitude, or certainty of evidence.
Overlap assessment
The overlap assessment was performed to inform interpretation of the overall conclusions by identifying the extent to which primary studies were repeatedly included across systematic reviews. Primary study identifiers extracted from each systematic review were standardized using canonical study identifiers to account for differences in citation formats and publication years, and a citation matrix was constructed. The corrected covered area (CCA) was then calculated to quantify the degree of overlap among primary studies included in multiple reviews.
Because an overall CCA may be diluted when reviews address unrelated clinical conditions, CCA was also calculated separately for each health condition category represented by more than one review. Overlap was not used as an exclusion criterion, and repeated inclusion of the same primary study was not interpreted as independent confirmation of treatment effects.
Pairwise CCA was also calculated for every pair of included reviews using the citation matrix. For two reviews, pairwise CCA equals the number of shared primary studies divided by the number of distinct primary studies in their combined set, multiplied by 100. Results were summarized separately for pairs within the same health condition category and pairs across categories.
Results
Overview of evidence base
A total of 100 reviews were included in this umbrella review (Fig. 1), representing 1,164 eligible primary-study occurrences and a cumulative reported sample size of 47,228 across reviews with reported values. After standardization and deduplication of study identifiers, 790 unique eligible primary studies were identified.
The distribution of countries by the first authors showed that most reviews were from Brazil (n = 23, 23.0%) and China (n = 21, 21.0%), followed by India (n = 7, 7.0%), Iran (n = 7, 7.0%), and Chile (n = 6, 6.0%). Smaller contributions came from the United States (n = 5, 5.0%), United Kingdom (n = 4, 4.0%) and Spain (n = 4, 4.0%), with the remaining reviews distributed across several other countries. The reviews were published between 2006 and 2026, with a median publication year of 2021 (IQR, 2019–2023).
The most productive years were 2021, 2023, and 2025 (n = 13 each), followed by 2022 (n = 12).
Fig. 1Flow diagram of systematic review identification, screening, eligibility assessment, and inclusion
When categorized according to the underlying health condition, the largest category was oral and dental conditions (n = 53, 53.0%), followed by musculoskeletal disorders (n = 22, 22.0%). Other categories included oncology-related complications (n = 8, 8.0%), wound and lymphatic conditions (n = 8, 8.0%), ocular conditions (n = 4, 4.0%), dermatologic and hair conditions (n = 3, 3.0%), respiratory conditions (n = 1, 1.0%), and auditory conditions (n = 1, 1.0%). This distribution indicates that more than half of the available review evidence on LLLT has focused on oral and dental applications, whereas non-oral indications were less frequently represented (Table 1).
Table 1General characteristics of the included systematic reviews (n = 100)First author, yearCountryCategoryHealth conditionNo. of included primary studiesReported sample sizeDirection of review authors’ conclusionsDevice typeDiode subtypeWavelength range (nm)Fluence range (J/cm2)Energy per point (J)Mode (continuous or pulsed)Adverse events reportedAbesi 2023IranOral and dental conditionsPost-gingivectomy wound healing and pain6140FavorableLaser (diode)Unspecified588–9404NRContinuousNRAhmad 2021IndiaMusculoskeletal disordersTemporomandibular joint disorders371409NeutralLaser (diode, He-Ne, Nd: YAG)AlGaInP, GaAlAs, GaAs,632.8–10641.5–112.5NRNRNRAhmed 2020IndiaOral and dental conditionsRecurrent aphthous ulcers5330FavorableLaser (diode, Nd: YAG)AlGaInP, unspecified658–1064NRNRNRNoAkram 2018aPakistanOral and dental conditionsOral lichen planus5240NeutralLaser (diode)AlGaInP630–9701.5–120NRNRNRAkram 2018bPakistanOral and dental conditionsGingival recession defects4100NeutralLaser (diode)GaAlAs588–8104–15NRNRNRAl-Maweri 2018Saudi ArabiaOral and dental conditionsRecurrent herpes labialis6492FavorableLaser (diode, He-Ne)GaAlAs632.5–8702.04–48NRNRNoAlosaimi 2025Saudi ArabiaDermatologic and hair conditionsAndrogenetic alopecia4165NeutralUnspecified LLLT-NRNRNRNRNRAnschau 2019BrazilOncology-related complicationsCancer therapy–induced oral mucositis5317FavorableUnspecified LLLT-830–9702–6.5NRNRNoBakdach 2020SyriaOral and dental conditionsOrthodontic tooth movement25570FavorableMixed (diode, LED)GaAlAs, GaAs618–9800.065–1500.2–2.3MixedNRBarbosa 2022BrazilOral and dental conditionsPost-orthognathic surgery pain, oedema, and neurosensory disorders15322FavorableLaser (diode)AlGaInP, GaAlAs, GaAs660–9801.5–157.51.2–9NRNRBarros 2022BrazilOral and dental conditionsHerpes labialis8931FavorableUnspecified LLLT-632.8–10722.04–48NRNRNRBekhet 2017EgyptMusculoskeletal disordersCarpal tunnel syndrome8473NeutralLaser (diode & unspecified)GaAlAs780–8806–112.7–11MixedNoBitencourt Reis 2022BrazilOral and dental conditionsOrthodontic tooth movement9164NeutralMixed (LED, diode)GaAlAs618–9805–67.061NRNRBittencourt 2017BrazilOral and dental conditionsNeurosensory disorders after orthognathic surgery350FavorableLaser (diode)GaAlAsNR5–70NRNRNRBonacina 2026BrazilOral and dental conditionsPostoperative endodontic pain8609FavorableLaser (diode)AlGaInP, GaAlAs, unspecified660–9806–590NRNRNRCabrera Martimbianco 2020BrazilMusculoskeletal disordersAchilles tendinopathy4119NeutralLaser (diode & unspecified)GaAlAs810–904NR0.9–3.0NRNoCarneiro 2022BrazilOral and dental conditionsTooth sensitivity after dental bleaching6212FavorableUnspecified LLLT-660–81010–60NRNRNoChen 2019ChinaOral and dental conditionsPostoperative pain after root canal treatment7446NeutralLaser (diode)AlGaInP800–97070–901.08–15MixedNoChen 2020TaiwanAuditory conditionsTinnitus11670NeutralUnspecified LLLT-650–830NRNRNRYesCheung 2020China (Hong Kong)Musculoskeletal disordersCarpal tunnel syndrome6418NeutralLaser (diode)AlGaInP, GaAlAs, GaAs660–9041–100.072–3.6NRYesda Silva Mira 2023BrazilOral and dental conditionsPediatric dental conditions4257FavorableUnspecified LLLT-786.94–9803–33.51–4NRNRde Figueiredo Costa 2021BrazilOral and dental conditionsOrthodontic mini-implant stability6108FavorableLaser (diode)Unspecified618–9404–36NRNRNRde la Barra Ortiz 2025ChileMusculoskeletal disordersDe Quervain tenosynovitis8320FavorableLaser: diode, unspecifiedGaAlAs830–9040.25–203–24ContinuousNRde la Barra Ortiz 2026ChileMusculoskeletal disordersMusculoskeletal disorders221352NeutralLaser: diode, unspecifiedUnspecified775–9804–50NRMixedNode Pedro 2020SpainOral and dental conditionsNeuropathic orofacial pain13405FavorableLaser (diode, He-Ne, unspecified)GaAlAs630–9802–105NRNRNoDeana 2017ChileOral and dental conditionsOrthodontic pain20788FavorableLaser (diode)GaAlAs, GaAs780–9401–1600.2–12MixedNoDelaney 2018USADermatologic and hair conditionsAndrogenetic alopecia5523FavorableUnspecified LLLT-630–66047.9–67.3NRNRYesDeng 2024ChinaOcular conditionsMyopia progression6793FavorableUnspecified LLLT-650NRNRNRYesDiaz 2025aChileOral and dental conditionsMaxillofacial neuropathies181220FavorableUnspecified LLLT-630–9802–20NRNRYesDiaz 2025bChileMusculoskeletal disordersTemporomandibular disorders441816FavorableUnspecified LLLT–632.8–10640.13–603–18MixedYesDoiphode 2024IndiaOral and dental conditionsPrimary molar pulpotomy14462NeutralLaser (diode & unspecified)Unspecified632–9802.5–6.7NRMixedNRDomah 2021United KingdomOral and dental conditionsThird molar surgery postoperative morbidity171094NeutralLaser (diode, He-Ne)GaAlAs, unspecified550–9403–126–106MixedNRDomingos de Barros 2022BrazilOral and dental conditionsPostoperative pain after lower third molar extraction15648FavorableLaser (diode)GaAlAs, unspecified550–9803–480NRNRNRdos Santos 2021BrazilWound and lymphatic conditionsDiabetic foot ulcers13361FavorableUnspecified LLLT-400–9041.5–10NRNRNoDuarte de Oliveira 2021BrazilOral and dental conditionsThird molar surgery postoperative pain, edema, trismus10308NeutralLaser (diode, He-Ne)AlGaInP, unspecified660–9403–187.56–180NRNRFan 2024ChinaMusculoskeletal disordersKnee osteoarthritis12631FavorableMixed (LED, diode)NR650–1,0601.5–382NRNRNRFarzan 2021IranOral and dental conditionsOrthodontic separator placement pain4129FavorableLaser (diode)GaAlAs810–8302–6NRNRNRFarzan 2022IranOral and dental conditionsBone formation in rapid palatal expansion485FavorableLaser (diode)AlGaInP, GaAlAs, unspecified660–980140–238.853–6NRNRFerreira Gonzalez 2025SpainOral and dental conditionsThird molar extraction complications18585NeutralLaser (diode)Unspecified660–9403–2124–50NRNRFiroozi 2020IranOral and dental conditionsNeurosensory disturbance after sagittal split ramus osteotomy (SSRO)8188NeutralMixed (LED, diode)GaAlAs632–9801.5–1001.2–9NRNoFranco 2023ItalyOncology-related complicationsOral mucositis after hematopoietic stem cell transplantation398FavorableUnspecified LLLT-NRNRNRNRNoGaitero 2025BrazilWound and lymphatic conditionsNipple trauma and pain3193NeutralUnspecified LLLT–6605-66.60.2–3NRYesGao 2025ChinaOral and dental conditionsOrthodontic pain231007FavorableUnspecified LLLT–808–8301–4NRNRNRGe 2015ChinaOral and dental conditionsOrthodontic tooth movement acceleration8121NeutralLaser (diode, He-Ne)GaAlAs, GaAs632–8602.5–25NRNRNoGentile 2024ItalyDermatologic and hair conditionsAndrogenetic alopecia (male and female pattern hair loss)7607FavorableMixed (LED, diode)Unspecified630–66047.9–67.3NRNRYesGhaderi 2025IranOral and dental conditionsDental pain5207FavorableLaser: diodeGaAlAs, Unspecified660–9804–692–16.25ContinuousNoGil 2025ChileOral and dental conditionsOral surgery17731FavorableLaser: diode, Nd: YAG, unspecifiedGaAlAs, InGaAIP, Unspecified660–10643–35NRMixedNRGolez 2022SloveniaOncology-related complicationsXerostomia/hyposalivation18558FavorableMixed (LED, diode, He-Ne)Unspecified625–9401.5–29.5NRMixedNoGrajales 2023SpainOral and dental conditionsOrthodontic tooth movement acceleration19305FavorableLaser (diode)GaAlAs, GaAs658–9804.2–25NRNRNRGuedes Pereira Máximo 2022BrazilMusculoskeletal disordersTemporomandibular disorder10438FavorableLaser (diode & unspecified)AlGaInP, GaAlAs, unspecified630–9041–1056NRNRHe 2013ChinaOral and dental conditionsOrthodontic pain6402NeutralLaser (diode, He-Ne)GaAlAs, unspecified632.8–8300.45–2.5NRContinuousNoHe 2015ChinaOral and dental conditionsPostoperative complications after mandibular third molar surgery12193FavorableLaser (diode, He-Ne, unspecified)GaAlAs, unspecified632.8–9804–100.96–54MixedNoHe 2018ChinaOncology-related complicationsChemotherapy-induced oral mucositis8373FavorableLaser (diode & unspecified)AlGaInAs, AlGaInP, GaAlAs660–9704–720.35–2.4NRNRHenein 2021United KingdomOcular conditionsAge-related macular degeneration2132UnclearMixed (LED, diode)Unspecified590–8504–9NRContinuousNRJajarm 2018IranOral and dental conditionsOral lichen planus7NRNeutralUnspecified LLLT-NRNRNRNRNRJimenez 2024USAMusculoskeletal disordersSpastic cerebral palsy8NRFavorableUnspecified LLLT-NRNRNRContinuousNRJing 2021ChinaMusculoskeletal disordersTemporomandibular joint disorders16538FavorableLaser (diode, He-Ne, Nd: YAG, unspecified)AlGaInP, GaAlAs, GaAs632.8–1064NRNRNRNRJnaneshwar 2023IndiaOral and dental conditionsOrthodontic tooth movement10223FavorableLaser (diode) & unspecified LLLTGaAlAs, unspecified618–9802.25–150NRContinuousNRJoseph 2025FinlandOncology-related complicationsOral mucositis in cancer patients5256FavorableLEDInGaAIP, GaAIP, unspecified600–6700.99–40.24–2.34ContinuousNRLi 2015ChinaOral and dental conditionsOrthodontic pain11698NeutralLaser (diode, He-Ne)AlGaInP, GaAlAs, GaAs, unspecified632.8–9100.5–60.042–10.88NRNRLi 2018ChinaWound and lymphatic conditionsDiabetic foot ulcer7194FavorableUnspecified LLLT-400–9042–10NRNRNoLourinho 2023BrazilMusculoskeletal disordersRheumatoid arthritis18793NeutralLaser (diode, He-Ne, unspecified)AlAs, GaAlAs632.5–10600.0075–251.55–7.5NRYesLu 2023ChinaOral and dental conditionsBurning mouth syndrome14550NeutralLaser (diode, Nd: YAG, unspecified)GaAlAs, unspecified630–10641–2002–6MixedNoLu 2025ChinaOral and dental conditionsOral lichen planus pain12476FavorableUnspecified LLLT–630–9800.3–177NRNRNoMachado 2017BrazilWound and lymphatic conditionsPressure ulcers4210NeutralLaser (diode & unspecified)GaAlAs, GaAs650–9501–4.5NRNRNRMalik 2023IndiaMusculoskeletal disordersKnee osteoarthritis13774FavorableMixed (LED, diode)GaAs, GaAlAs, unspecified640–9050.12–2001.2–30NRNRMeneses-Santos 2022BrazilOral and dental conditionsPostoperative outcomes after orthognathic surgery5190NeutralLaser (diode)InGaAsP, GaAlAs660–9403–1001.2–2.8MixedNRMichelogiannakis 2022USAOral and dental conditionsOrthodontic mini-screw implant stability6103FavorableLaser (diode)Unspecified618–940NRNRPulsedNRMirzaei 2019GermanyOral and dental conditionsInferior alveolar nerve sensory recovery after sagittal split osteotomy7181FavorableLaser (diode)GaAlAs660–9301.5–1001.2–9NRNRMunguia 2018USAMusculoskeletal disordersTemporomandibular myofascial pain8225NeutralLaser (diode, Nd: YAG)AlGaInP, GaAlAs, GaAs660–10643.4–105NRMixedNRNascimento Ribeiro 2024BrazilOncology-related complicationsXerostomia in head and neck radiotherapy patients4126NeutralLaser (diode)AlGaInP, GaAlAs660–8303–710.28–2NRNRPeralta-Mamani 2019BrazilOncology-related complicationsOral mucositis due to radiotherapy for head and neck cancer7363FavorableLaser (diode, He-Ne)AlGaInP632.8–6851.3–6.30.05–3NRNRPrados-Frutos 2016SpainOral and dental conditionsDental implant220UnclearLaser (diode)GaAlAs637–8306.26–92.10.25MixedNRRadithia 2024IndiaOral and dental conditionsRecurrent aphthous stomatitis8424FavorableLaser (diode, Nd: YAG)AlGaInP, GaAlAs, unspecified645–10642–12.90.1–3MixedNRRankin 2017United KingdomMusculoskeletal disordersCarpal tunnel syndrome221153NeutralLaser (diode, He-Ne, Nd: YAG)GaAlAs, GaAs, unspecified632.7–10643.4–111.2–8MixedNoReis Guerreiro 2021BrazilOral and dental conditionsPostoperative endodontic pain12736FavorableMixed (LED, diode)AlGaIn, GaAlAs, unspecified640–9703–902.5MixedNRRen 2015China (Hong Kong)Oral and dental conditionsOrthodontic pain14659NeutralLaser (diode)AlGaInP, GaAlAs, GaAs, unspecified635–9100.5–800.18–9MixedNoRen 2022ChinaMusculoskeletal disordersTemporomandibular disorders pain27969FavorableUnspecified LLLT-632.8–11001.5–1051.5–2NRNRShafaee 2023IranOral and dental conditionsOral health in fixed orthodontic patients6142NeutralLaser (diode)GaAlAs, unspecified660–940NR2–5.7ContinuousNRShan 2021ChinaOral and dental conditionsDentin hypersensitivity35574FavorableLaser (diode, Nd: YAG) & unspecified LLLTGaAlAs, unspecified630–10672–1000.1–300ContinuousNRSkondra 2018GreeceOral and dental conditionsBone healing and regeneration after rapid maxillary expansion493FavorableLaser (diode)GaAlAs, unspecified660–83010–140NRNRNRSobral de Oliveira-Souza 2023BrazilOral and dental conditionsOrofacial pain89NRFavorableMixed (LED, diode, He-Ne, Nd: YAG) & unspecified LLLTAlGaInP, GaAlAs, GaAs, unspecified632.8–10643–112.5NRNRNRSouza de Lima 2020BrazilOncology-related complicationsOral mucositis prevention in head and neck cancer patients4500FavorableLaser (diode, He-Ne)AlGaInP, GaAlAs632.8–6602.5–40.1–3.48NRNRStausholm 2019NorwayMusculoskeletal disordersKnee osteoarthritis221063FavorableUnspecified LLLT-785–904NR0.054–8NRNoTaha 2024United KingdomWound and lymphatic conditionsSkin wounds18670FavorableLaser (diode) & unspecified LLLTAlGaInP, GaAlAs, unspecified400–8901.04–13NRMixedNRTang 2023ChinaOcular conditionsMyopia131857FavorableUnspecified LLLT-635–650NRNRNRNoTchanque-Fossuo 2016USAWound and lymphatic conditionsDiabetic foot ulcer4131FavorableUnspecified LLLT-400–8902–43.2NRNRNoTripodi 2021AustraliaMusculoskeletal disordersTendinopathy17835NeutralUnspecified LLLT-810–9050.5–5NRNRNoVande 2022IndiaOral and dental conditionsDental implant stability10156NeutralMixed (LED, diode, unspecified)GaAlAs, unspecified626–9804–92.1NRNRNRVlassov 2006RussiaRespiratory conditionsTuberculosis1130UnclearLaser (diode)GaAs890NRNRNRNRWahid 2024IndonesiaWound and lymphatic conditionsPost-mastectomy lymphedema9299FavorableUnspecified LLLT-NRNRNRNRNoWang 2019ChinaMusculoskeletal disordersPlantar fasciitis6274FavorableLaser (diode)GaAlAs, GaAs, unspecified635–904NR5.6–16.8NRNoYang 2025ChinaOcular conditionsChildhood myopia81479FavorableUnspecified LLLT-650NRNRNRYesYap 2025SingaporeMusculoskeletal disordersPain in tendinopathy351551FavorableLaser-633–10600.38–303–16MixedNRYeh 2019TaiwanMusculoskeletal disordersFibromyalgia9325FavorableMixed (LED, diode) & unspecified LLLTGaAlAs, GaAs640–9502–42–4MixedNoYousefi-Nooraie 2008CanadaMusculoskeletal disordersNon-specific low back pain7384UnclearLaser (diode, Nd: YAG, unspecified)GaAlAs, GaAs, unspecified632–1060NR0.1–29.9MixedNoZhao 2021ChinaOral and dental conditionsPostoperative pain and wound healing after periodontal surgery13394NeutralMixed (LED, diode)GaAlAs, unspecified588–9404–60NRNRYesZheng 2023aChinaOral and dental conditionsOrthodontic dental alignment8369FavorableMixed (LED, diode)GaAlAs, InGaAs635–9802.25–216NRContinuousNRZheng 2023bChinaOral and dental conditionsOrthodontic miniscrew stability346NeutralMixed (LED, diode)Unspecified618–94036NRNRNRZhou 2021SingaporeWound and lymphatic conditionsDiabetic foot ulcers12480FavorableUnspecified LLLT-400–9040.18–10NRMixedNo
Regarding the direction of review authors’ conclusions, 62 reviews (62.0%) reached overall conclusions favoring the evaluated intervention, 34 (34.0%) reported neutral or mixed conclusions, and 4 (4.0%) had unclear conclusions. The highest within-category proportions of favorable conclusions were observed for oncology-related complications (87.5%), wound and lymphatic conditions (75.0%), and ocular conditions (75.0%) (Table 2).
Table 2Evidence size and direction of review authors’ conclusions by health condition categoryHealth condition categoryNo. of reviewsNo. of primary study occurrencesNo. of unique primary studiesCumulative reported sample sizeDirection of review authors’ conclusions (review count, %)Oral and dental conditions5362444519,883Favorable: 32 (60.4%), Neutral: 20 (37.7%), Unclear: 1 (1.9%)Musculoskeletal disorders2235925715,860Favorable: 12 (54.5%), Neutral: 9 (40.9%), Unclear: 1 (4.5%)Oncology-related complications854462,591Favorable: 7 (87.5%), Neutral: 1 (12.5%)Wound and lymphatic conditions870462,538Favorable: 6 (75.0%), Neutral: 2 (25.0%)Ocular conditions429224,261Favorable: 3 (75.0%), Unclear: 1 (25.0%)Dermatologic and hair conditions316111,295Favorable: 2 (66.7%), Neutral: 1 (33.3%)Respiratory conditions111130Unclear: 1 (100.0%)Auditory conditions11111670Neutral: 1 (100.0%)Total1001,164790*47,228Favorable: 62 (62.0%), Neutral: 34 (34.0%), Unclear: 4 (4.0%)Percentages are calculated within each health condition categoryReported sample size is presented as reported for eligible primary studies and may refer to participants, teeth, or other units of analysis. Three reviews did not report a total sample size. Review-level sample sizes were summed across reviews and may include the same participants more than once because some primary studies were represented in multiple reviews.
Accordingly, the cumulative reported sample size of 47,228 should not be interpreted as the number of unique participants. Category-level primary-study occurrences were summed across reviews, whereas unique primary studies were deduplicated separately within each health condition category. Direction categories reflect the conclusions reported by the review authors* Category-specific unique primary-study counts are not mutually exclusive because some primary studies were represented in systematic reviews assigned to more than one category.
After accounting for this cross-category overlap, the overall number of unique primary studies was 790
Oral and dental conditions
Oral and dental conditions contributed the largest body of evidence, with 53 reviews [16–68] including 624 eligible primary-study occurrences representing 445 unique primary studies. Of these, 32 reviews (60.4%) reached favorable conclusions, 20 (37.7%) reported neutral conclusions, and 1 review (1.9%) was classified as unclear. Favorable conclusions were most commonly reported for post-surgical healing and pain control, recurrent herpes labialis, and some orthodontic applications.
Neutral conclusions were reported across several indications, including oral lichen planus, gingival recession, implant stability, and some postoperative dental outcomes.
Musculoskeletal disorders
Twenty-two reviews [69–90] included 359 eligible primary-study occurrences representing 257 unique primary studies on musculoskeletal disorders, including temporomandibular disorders, tendinopathy, osteoarthritis, carpal tunnel syndrome, low back pain, fibromyalgia, and related pain conditions. Twelve reviews (54.5%) reached favorable conclusions, 9 (40.9%) reported neutral conclusions, and 1 (4.5%) was classified as unclear. Favorable conclusions were most commonly reported for pain reduction and functional improvement in selected musculoskeletal conditions, whereas neutral conclusions were frequently reported in reviews with substantial variation in treatment parameters, comparator interventions, and outcome assessment.
Oncology–Related complications
Eight reviews [91–98] included 46 unique primary studies on oncology-related complications, most commonly oral mucositis and xerostomia associated with chemotherapy or radiotherapy. Seven reviews (87.5%) reached favorable conclusions, and 1 (12.5%) review reported neutral conclusions. Favorable conclusions were mainly reported for reducing the incidence, severity, or duration of oral mucositis.
Dermatologic and hair conditions
Three reviews [99–101] included 11 unique primary studies in dermatologic and hair conditions. Two reviews (66.7%) reached favorable conclusions and 1 (33.3%) reported neutral conclusions. The two favorable reviews evaluated hair density outcomes, whereas the review evaluating hair count and diameter was neutral.
Wound care and lymphatic disorders
Eight reviews [102–109] included 46 unique primary studies on wound and lymphatic conditions, including diabetic foot ulcers, pressure ulcers, skin wounds, post-mastectomy lymphedema, and nipple trauma and pain. Six reviews (75.0%) reached favorable conclusions and 2 (25.0%) reported neutral conclusions. Favorable conclusions were primarily related to wound healing, tissue repair, or edema reduction.
Ocular conditions
Four reviews [110–113] included 22 unique primary studies related to ocular conditions, including myopia progression, childhood myopia, and age-related macular degeneration. Three reviews (75.0%) reached favorable conclusions and 1 (25.0%) was classified as unclear. Favorable conclusions were reported mainly in myopia-related applications.
Respiratory conditions
Respiratory conditions were represented by 1 review [114], including 1 primary study on tuberculosis. This review was classified as unclear.
Auditory conditions
Auditory conditions were represented by 1 review [115], including 11 primary studies on tinnitus. This review was classified as neutral.
Primary outcome domains
The primary outcomes reported across the included systematic reviews were categorized into five outcome domains. Pain was the most frequently evaluated primary outcome domain (57 reviews), followed by functional outcomes (27 reviews), healing or disease severity (26 reviews), structural outcomes (19 reviews), and biological outcomes (3 reviews). The full list of primary outcomes reported by the included systematic reviews is provided in Supplementary Table S1.
Distribution of review conclusions across health conditions
A bubble map was constructed to visualize the distribution of review conclusions across health condition categories (Fig. 2). The x-axis represents the direction of review authors’ conclusions (favorable, neutral, or unclear), and the y-axis lists the health condition categories, with the number of included reviews in parentheses.
Bubble size reflects the number of reviews, while the labels show the review count and within-category percentage.
Fig. 2Bubble map of the direction of review conclusions across health condition categories
Adverse events
Fifty-seven reviews (57.0%) did not provide adverse-event information. Among the 43 reviews that addressed adverse events or side effects, 32 reviews (32.0% of all reviews) explicitly reported no adverse events, whereas 11 (11.0%) reported one or more events (Table 3). Reported events included local discomfort and skin reactions, such as erythema, warmth, burning, tingling, pruritus, dry skin, scalp irritation, acne, and pain.
Other reported events included sudden deafness with dizziness, increased disease activity, and prolonged afterimage duration. However, the included reviews generally did not provide sufficient denominators, comparator-group data, causality assessments, standardized severity classifications, or absolute risks. Therefore, the frequency, comparative risk, severity, and relationship of these events to LLLT could not be determined.
Table 3Review-level reporting of adverse events by health condition categoryHealth condition categoryAENo AENRReported adverse events or side effectsOral and dental conditions21437Pain, discomfort, burning sensation, edema, erythema (13 RCTs); transient erythema or warmth at application site (< 5%).Musculoskeletal disorders3910Mild wrist pain and discomfort (1 RCT); increased disease activity and burning sensation in treated joints (2 RCTs); transient erythema (3–5%) and mild discomfort at application site (< 2%)Oncology-related complications035-Wound and lymphatic conditions152Tingling sensation (1 RCT)Ocular conditions211Discomfort from brightness (1 RCT); excessive afterimage duration (1 RCT)Dermatologic and hair conditions201Xerosis, pruritus, mild scalp irritation, warm sensation, acne (2 RCTs); paresthesia, mild urticaria, headache, dry skin, pruritus, scalp tenderness, irritation, warm sensation, eczema, acne (4 RCTs)Respiratory conditions001-Auditory conditions100Sudden deafness and dizziness (1 RCT)Total113257AE adverse events, NR not reported, RCT randomized controlled trialCounts represent systematic reviews rather than individual participants or adverse events. “NR” indicates that the review did not provide adverse-event information and should not be interpreted as the absence of adverse events. The reported events are presented as described in the included reviews
Methodological quality
Overall methodological confidence in the included reviews was generally low according to AMSTAR 2 (Table 4). Sixty reviews (60.0%) were rated as critically low, 30 (30.0%) as low, 1 (1.0%) as moderate, and 9 (9.0%) as high confidence. Item-level performance varied considerably.
Description of included studies (Q8) was rated Yes in 97 reviews and Partial Yes in 3, while PICO/inclusion criteria (Q1) was rated Yes in 99 reviews. Justification of eligible study designs (Q3) was rated Yes in 97 reviews. High adherence was also observed for disclosure of conflicts of interest (Q16, 93.0%), duplicate study selection (Q5, 90.0%), and duplicate data extraction (Q6, 86.0%).
In contrast, reporting of funding for the included primary studies (Q10) was rated Yes in only 6.0% of reviews.
Table 4AMSTAR 2 overall confidence summary (n = 100)Overall confidencen%High99.0Moderate11.0Low3030.0Critically low6060.0
Among the AMSTAR 2 critical domains, performance was lowest for provision of an excluded-study list with justification (Q7; 22.0% Yes) and assessment of publication bias (Q15; 23.0% Yes or Partial Yes). Ten reviews met all applicable critical domains; 9 were rated as high confidence and 1 as moderate confidence. The item-level judgments and overall confidence ratings, together with graphical summaries of the AMSTAR 2 domain-level judgments and overall confidence, are presented in Supplementary Material 2.
Overlap assessment
The citation matrix comprised 790 unique eligible primary studies and 1,164 primary-study occurrences across the included systematic reviews. The overall CCA was 0.48%. However, category-specific CCA values were used for interpretation, since the overall CCA value combined reviews addressing diverse unrelated conditions.
CCA was 22.73% for dermatologic and hair conditions, 10.61% for ocular conditions, 7.45% for wound and lymphatic conditions, 2.48% for oncology-related complications, 1.89% for musculoskeletal disorders, and 0.77% for oral and dental conditions. CCA was not applicable to the auditory and respiratory categories because each contained only one review. The citation matrix is provided in Supplementary Table S2.
Among 1,674 within-category review pairs, 144 shared at least one primary study. Pairwise CCA ranged from 0% to 71.43%, indicating substantial overlap between some individual reviews despite the low overall CCA. Fifteen cross-category pairs also shared primary studies.
Full pairwise results are provided in Supplementary Table S3.
Discussion
This umbrella review consolidated evidence from 100 systematic reviews on LLLT across diverse clinical conditions. A substantial proportion of the included reviews reached conclusions favoring the evaluated interventions, suggesting potential clinical benefit in selected indications. Nevertheless, the direction of review-level conclusions alone does not establish treatment efficacy or the certainty of the underlying evidence, and interpretation was further limited by the generally low methodological confidence of the included reviews.
Interpretation of key findings
Favorable review conclusions were most common for oncology-related complications, driven mainly by reviews of oral mucositis reporting reductions in its incidence, severity, or duration. This aligns with clinical practice guidelines that recommend LLLT for supportive oncology care [116, 117]. Oral and dental conditions contributed the largest body of review evidence, with favorable conclusions reported for post-gingivectomy healing, recurrent herpes labialis, and adjunctive periodontal care.
These favorable conclusions are consistent with the broader literature suggesting the potential of LLLT to promote oral healing and reduce pain [118, 119]. However, conclusions varied across indications, indicating that a larger volume of evidence did not correspond to uniformly favorable conclusions.
Across all included reviews, treatment parameters varied widely (wavelengths, 400–1,100 nm; fluence, 0.0075–590 J/cm²). This heterogeneity may have contributed to inconsistent findings across conditions and underscores the need for standardized protocols for light-based therapies. Furthermore, the cumulative reported sample size should not be interpreted as the number of unique participants due to overlap among systematic reviews and the use of units other than individual participants in some dental reviews.
Adverse events and safety considerations
Adverse-event reporting was incomplete across the included reviews. Fifty-seven reviews did not provide adverse-event information, which should not be interpreted as indicating that no adverse events occurred. Reviews addressing harms generally lacked consistent denominators, comparator-group data, causality assessments, standardized severity classifications, and absolute risks.
Although localized discomfort and skin reactions were reported, potentially important events, including sudden deafness with dizziness, increased disease activity, and prolonged afterimage duration, were also described. Consequently, no firm conclusions could be drawn about the incidence, comparative risk, causality, or overall safety of LLLT. Future trials and systematic reviews should systematically monitor and report adverse events, including comparator-specific denominators, severity, causality, and absolute risks, to enable more reliable safety assessments [120, 121].
Methodological quality and evidence certainty
Confidence in the review conclusions was limited because most systematic reviews received low or critically low overall confidence ratings using AMSTAR 2. Although many reviews performed well in core methodological domains, such as defining the review question, conducting literature searches, describing included studies, and assessing risk of bias, shortcomings in critical domains reduce confidence even when conclusions appear favorable. Limited protocol registration increases the risk of selective reporting, the absence of excluded-study lists reduces transparency, incomplete reporting of funding sources limits assessment of potential conflicts of interest, and insufficient evaluation of publication bias may overestimate treatment effects.
Because 90 of the 100 included reviews (90.0%) had low or critically low methodological confidence, the favorable conclusions should be interpreted cautiously and should not be viewed as evidence of high certainty.
Due to the substantial heterogeneity in outcomes and inconsistent reporting of pooled estimates across reviews, outcome-level quantitative synthesis and sensitivity analyses according to methodological quality were not feasible. Therefore, findings should be interpreted together with the overall methodological confidence. Although AMSTAR 2 provided an assessment of review conduct, it does not indicate the certainty of the underlying evidence or confidence in effect estimates.
Implications for clinical practice
Clinical application of LLLT should be considered on a condition-specific basis. Oral mucositis represents a particularly promising application, as favorable review conclusions were frequent and were consistent with existing clinical practice guidelines. Favorable conclusions were also reported for selected oral and dental, wound-related, musculoskeletal, ocular, and dermatologic indications, although findings were less consistent across these areas.
Given the generally low methodological confidence of the included reviews and substantial variation in treatment parameters and outcomes, clinical decisions should consider condition-specific evidence and guidance, treatment parameters, and patient characteristics rather than the number of reviews reaching favorable conclusions. The available evidence did not permit firm conclusions about safety, and cost-effectiveness was not evaluated in this umbrella review.
Research gaps and future directions
Future research should address several key gaps. First, intervention parameters should be standardized to reduce heterogeneity and enable more reliable comparisons among studies. Wavelength, power, fluence, treatment duration, and frequency should be clearly reported in clinical trials.
Second, larger, well-designed randomized controlled trials are needed. Third, future systematic reviews should improve methodological rigor through protocol registration, transparent reporting of excluded studies and funding sources, and assessment of publication bias. Finally, safety outcomes should be systematically assessed and reported, ensuring that risks are adequately evaluated alongside benefits.
Strengths and limitations
The primary strength of this umbrella review is its comprehensive synthesis of systematic reviews across diverse clinical applications of light therapy. By evaluating the evidence at the review level, this umbrella review provides a high–level overview of the breadth and credibility of the findings. However, this review has several limitations.
Although the overall CCA was 0.48%, this aggregate may obscure overlap within particular clinical areas because it combines reviews addressing diverse conditions. Category-specific overlap was considerably higher for dermatologic and hair conditions, ocular conditions, and wound and lymphatic conditions. Pairwise analysis further identified substantial overlap between some individual reviews, with within-category pairwise CCA reaching 71.43%.
Repeated inclusion of the same primary studies may therefore contribute to apparent consistency across review conclusions and should not be interpreted as independent confirmation of treatment effects. Although category-specific and pairwise analyses were performed, further stratification by specific condition, comparison, and outcome was not feasible because the available extracted data did not consistently link individual primary studies to these combinations. Establishing these links would have required additional extraction from the primary studies.
Broad health condition categories may therefore still obscure overlap within particular clinical questions.
In addition, the certainty of evidence (e.g., using GRADE) was not evaluated at the umbrella level, which limits the formal assessment of confidence in the effect estimates. The descriptive classification of review authors’ conclusions was intended to provide a broad overview across diverse clinical conditions but did not account for differences in sample size, methodological quality, or strength of evidence among reviews. Consequently, reviews with substantially different evidentiary weight contributed equally to the summary findings, potentially oversimplifying the evidence base.
The findings should therefore be interpreted alongside the AMSTAR 2 and overlap assessments. Additionally, variability in outcome measures, patient populations, and intervention parameters limited the ability to draw firm conclusions for several conditions and also limited the assessment of dose-response relationships. Finally, publication bias could not be assessed at the umbrella level, leaving the possibility that favorable conclusions are overrepresented.
Conclusions
The included reviews reported favorable conclusions for several clinical conditions, with the clearest positive pattern observed for oncology-related complications, particularly oral mucositis. These findings suggest that LLLT has potential clinical value in selected indications and identify areas in which further clinical development and research may be warranted. However, these descriptive patterns do not establish treatment efficacy or certainty of evidence.
Interpretation remains limited by heterogeneity in treatment protocols, incomplete adverse-event reporting, the absence of an umbrella-level certainty assessment, and the generally low methodological confidence of the included reviews. Future research should build on these promising areas while prioritizing standardized protocols, rigorous study designs, and higher-quality evidence syntheses.
Supplementary Information
Below is the link to the electronic supplementary material.
Supplementary Material 1
Supplementary Material 2
Supplementary Material 3
Supplementary Material 4
Supplementary Material 5