Abstract
In-office tooth bleaching is widely used for rapid aesthetic improvement, but the clinical value of protocol variations—such as peroxide concentration, light activation, gel application methods, and desensitizing strategies—remains uncertain. This umbrella review synthesized systematic reviews and meta-analyses evaluating the effects of in-office bleaching protocols on whitening efficacy and tooth sensitivity. PubMed, Scopus, and Web of Science were searched from database inception to January 2026. Eligible studies were systematic reviews or meta-analyses assessing in-office bleaching of vital permanent teeth in adults. Methodological quality was assessed using AMSTAR-2, and certainty of evidence for major clinical questions was evaluated using GRADE. Due to protocol heterogeneity, findings were synthesized narratively with emphasis on results from higher-quality reviews. Twenty-four systematic reviews were included. Moderate-certainty evidence indicated that low-to-medium hydrogen peroxide concentrations (≈25–35%) produce whitening outcomes comparable to higher concentrations while reducing tooth sensitivity. Light activation (LED, halogen, or laser) generally did not improve whitening efficacy and may increase sensitivity. A recent meta-analysis suggested that violet-light activation combined with carbamide peroxide may enhance whitening without increasing sensitivity; however, supporting evidence remains limited. Single gel application protocols showed similar whitening outcomes to repeated gel renewals, with a tendency toward lower sensitivity. Desensitizing agents, particularly potassium nitrate and sodium fluoride, consistently reduced sensitivity without affecting whitening efficacy. Moderate peroxide concentrations, simplified gel application strategies, and desensitizing approaches may optimize in-office bleaching while minimizing sensitivity. Evidence supporting light activation and photobiomodulation remains limited, highlighting the need for well-designed randomized clinical trials.
Supplementary Information
The online version contains supplementary material available at 10.1007/s44445-026-00159-7.
Keywords: Bleach, Esthetic dentistry, Peroxide hydrogen
Introduction
Tooth discoloration is a common aesthetic concern that may negatively affect self-image and oral-health–related quality of life (Rodríguez-Martínez et al. 2019). Consequently, tooth whitening has become one of the most frequently requested cosmetic dental procedures. Vital tooth bleaching using peroxide-based agents is widely considered a minimally invasive approach for improving dental aesthetics while preserving natural tooth structure (Kielbassa et al. 2015).
Among available techniques, in-office bleaching allows rapid shade improvement under professional supervision through the use of high-concentration hydrogen peroxide or carbamide peroxide formulations (Kothari et al. 2019). Despite its effectiveness, tooth sensitivity remains the most frequently reported adverse effect associated with bleaching procedures and represents the main factor limiting patient comfort and treatment acceptance (Kielbassa et al. 2015; Goettems et al. 2021).
To improve outcomes and reduce adverse effects, numerous modifications of in-office bleaching protocols have been proposed. These include variations in peroxide concentration, different gel application strategies, the use of desensitizing agents, and adjunctive technologies such as light activation systems (e.g., LED, halogen, laser, and violet light) (He et al. 2012; Joiner 2010). However, the true clinical value of many of these protocol modifications remains debated.
Over the past decade, several systematic reviews and meta-analyses have evaluated the effects of these protocol variables on whitening efficacy and tooth sensitivity. Although some reviews reported potential advantages for certain techniques, others found little or no clinically meaningful differences between protocols (Joiner 2010; Page et al. 2021; Maran et al. 2018). In addition, methodological limitations such as heterogeneous study designs, variability in outcome measures, and inconsistent risk-of-bias assessment have contributed to uncertainty in the interpretation of existing evidence.
Umbrella reviews synthesize evidence from multiple systematic reviews and can provide a comprehensive overview of the strength and consistency of the available literature. Therefore, the aim of this umbrella review was to critically synthesize systematic reviews and meta-analyses evaluating in-office tooth bleaching protocols, with particular emphasis on peroxide concentration, light activation, gel application strategies, desensitizing approaches, and adjunctive therapies, while also assessing the methodological quality and certainty of the evidence.
Materials and methods
Protocol and reporting
This umbrella review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement for systematic reviews of systematic reviews (Page et al. 2021). The methodological framework, eligibility criteria, and outcomes of interest were defined a priori before study selection and data extraction in order to ensure methodological transparency and reproducibility.
Although prospective registration of systematic review protocols in PROSPERO is recommended, umbrella reviews synthesizing previously published systematic reviews are not consistently accepted within the PROSPERO database, which primarily focuses on reviews of primary clinical studies. For this reason, the protocol for the present review was not prospectively registered. Nevertheless, all methodological decisions, eligibility criteria, and analytical procedures were defined prior to data collection and are fully described in this manuscript to ensure transparency.
Eligibility criteria
Systematic reviews and meta-analyses were considered eligible if they evaluated in-office tooth bleaching procedures performed on vital permanent teeth in adult patients. Included reviews were required to investigate bleaching protocols involving hydrogen peroxide or carbamide peroxide and to report at least one clinically relevant outcome related to whitening efficacy, such as color change measured by ΔE or ΔSGU, and/or tooth sensitivity.
Reviews were excluded if they were narrative or scoping reviews without systematic methodology, focused exclusively on at-home bleaching techniques, investigated non-vital or intracoronal bleaching, or relied solely on in vitro evidence without clinical data. Reviews that did not clearly report their search strategy or eligibility criteria were also excluded in order to maintain methodological consistency.
Information sources and search strategy
A comprehensive electronic literature search was conducted in PubMed, Scopus, and Web of Science from database inception to January 2026, without restrictions regarding publication year or language. The search strategy combined controlled vocabulary terms and free-text keywords related to in-office tooth bleaching, hydrogen peroxide, carbamide peroxide, tooth whitening, tooth sensitivity, light activation, and systematic reviews or meta-analyses.
To minimize the risk of publication bias, additional screening of grey literature sources, including Google Scholar, was performed. The reference lists of all eligible systematic reviews were also examined to identify potentially relevant studies that might not have been retrieved through the database search. The complete electronic search strategies for each database are presented in Supplementary Table S1.
Study selection
All retrieved records were exported to Rayyan® systematic review software to facilitate duplicate removal and screening. Study selection was performed in two stages. Initially, titles and abstracts were screened to exclude clearly irrelevant records. Subsequently, full-text articles of potentially eligible studies were assessed according to the predefined eligibility criteria.
Any disagreements during the selection process were resolved through discussion and consensus. The overall study-selection process, including the number of records identified, screened, excluded, and finally included, is illustrated in the PRISMA flow diagram (Fig. 1).
Fig. 1.

PRISMA flow diagram of study selection. Legend: Flow diagram depicting identification, screening, eligibility, and inclusion stages according to PRISMA 2020. Shows number of records retrieved, duplicates removed, exclusions after title/abstract screening, full-text exclusions with reasons, and final number of systematic reviews included (n = 24). Abbreviations: PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses
Data extraction
Data extraction was performed using a standardized form designed for this review. For each included systematic review, information was collected regarding the first author, year of publication, journal, and number and design of the primary studies included in the review. Additional data included the bleaching agents and concentrations evaluated, protocol variables such as light activation, gel application strategies, desensitizing agents, and photobiomodulation approaches, as well as reported outcomes related to whitening efficacy and tooth sensitivity.
Reported adverse effects associated with bleaching procedures were also recorded when available. The main characteristics and findings of the included systematic reviews are summarized in Table 1.
Table 1.
Characteristics of the included systematic reviews
| # | First author (Year) | Journal | Type | Population & setting | In-office protocol focus | Adjunct/comparison | Main outcomes | Key conclusion (simplified) |
|---|---|---|---|---|---|---|---|---|
| 1 | He (2012) | J Dent | SR + MA | Adults, vital teeth, in-office HP | In-office bleaching with HP | Light vs no light | ΔE/color, tooth sensitivity | Light activation does not provide clinically relevant improvement in color; associated with increased or similar sensitivity |
| 2 | Maran (2018) | J Dent | SR + MA | Adults, vital teeth | In-office HP gels | Light-activated vs non-light in-office | ΔE, tooth sensitivity | Activation of in-office gel with light does not improve color change or affect TS, regardless of HP concentration |
| 3 | SoutoMaior (2019) | Oper Dent | SR + MA | Adults, vital teeth | In-office bleaching | Various light sources (LED, laser, halogen, etc.) vs no light | ΔE, TS | Different light sources produce minimal additional bleaching; some associated with more sensitivity; overall benefit of light is limited |
| 4 | Casado (2020) | Oper Dent | SR + MA | Adults, in-office | In-office HP with light | Laser vs other light sources | Tooth sensitivity, ΔE | Laser has no significant advantage in TS or color change compared with other light sources during in-office bleaching |
| 5 | Kikly (2019) | J Esthet Restor Dent | SR | Adults, vital teeth | In-office, laser-activated bleaching | Laser-activated vs conventional protocols | Post-operative sensitivity | Laser-activated bleaching protocols tend to show higher or similar sensitivity; evidence not strong enough to justify routine use purely for TS benefits |
| 6 | Alshammery (2019) | J Contemp Dent Pract | SR | Adults | In-office HP | Light activation vs no light | ΔE, photosensitivity | Light activation does not consistently enhance whitening efficacy and may increase photosensitivity/TS |
| 7 | Maran (2019) | J Dent/Clin Oral Investig (NMA) | SR + network MA | Adults, in-office | In-office HP protocols | Multiple light-activation systems vs no light | ΔE | No light-activation protocol is superior to non-light in-office bleaching for efficacy, regardless of HP concentration |
| 8 | Ajaj (2012) | Dent Hypotheses | SR | Adults, in-office | In-office bleaching | Light/laser vs no light | Efficacy, TS | Early evidence-based SR suggesting no strong clinical justification for routine light/laser activation in in-office bleaching |
| 9 | Anagnostaki (2023) | Appl Sci | SR | Clinical + in vitro; vital teeth | Laser-activated vs conventional in-office bleaching | Laser protocols | Color, TS, protocol parameters | Laser-activated bleaching is not clearly superior to conventional in-office methods; protocols are heterogeneous and require standardization |
| 10 | Bessa (2025) | Lasers Med Sci | SR + MA | Adults, in-office | In-office bleaching with carbamide peroxide | Violet light-assisted vs conventional | ΔE, TS | Violet light can improve color change with no increase in sensitivity compared with conventional in-office CP bleaching |
| 11 | Maran (2020) | J Dent | SR + MA | Adults, in-office | HP concentration for in-office bleaching | Low/medium (< 35%) vs high (≥ 35%) HP | ΔE, TS | Low/medium HP provides similar color change with lower risk and intensity of TS than high-concentration HP |
| 12 | de Boa (2024) | Restor Dent Endod | SR | Adults, in-office | HP vs CP in-office bleaching | 35–38% HP vs high CP (e.g., 37%) | Efficacy, TS | In-office carbamide peroxide can achieve comparable whitening to HP with no higher TS, but evidence is limited |
| 13 | Kury (2022) | J Esthet Restor Dent | SR + MA | Adults, in-office | Single vs repeated gel application per session | Gel renewal vs single application | ΔE immediately/longer term, TS | No clinically significant difference in ΔE between renewal vs single application; TS may be lower with single application protocols |
| 14 | Wang (2015) | J Dent | SR + MA | Adults undergoing bleaching (in-office + at-home) | Bleaching with desensitizers | KNO₃ and NaF vs placebo/no desensitizer | TS (risk/intensity), color | Potassium nitrate and sodium fluoride reduce tooth sensitivity during bleaching; no consistent effect on color. Includes in-office subgroups |
| 15 | Krishnakumar (2022) | Cureus | SR + MA | Adults, in-office | In-office HP with pre-applied desensitizers | Various desensitizing agents prior to bleaching | TS, color | Pre-bleaching desensitizers reduce TS without compromising color in many protocols; evidence still moderate |
| 16 | Fachin (2023) | J Adv Med Med Res | SR + MA | Adults, in-office | In-office whitening | Different desensitizing agents during/around in-office bleaching | TS (odds ratio), ΔE | Various desensitizing agents significantly reduce TS in in-office whitening; color change preserved |
| 17 | Cabral (2024) | Clin Oral Investig (online first) | SR | Adults, in-office or at-home | Bleaching (incl. single-session in-office with 35–38% HP) | Desensitizing toothpastes vs control | TS | Desensitizing toothpastes reduce TS after some high-concentration bleaching regimens (including single-session in-office), but not all protocols |
| 18 | PBM SR – Rezende/Vochikovski group (~ 2022) | Photobiomodul Photomed Laser Surg | SR + MA | Adults, in-office | In-office bleaching with PBM/LLLT adjunct | PBM vs placebo | Pain-related symptoms, ΔE | Photobiomodulation reduces pain/TS without affecting bleaching efficacy |
| 19 | Giannakopoulou (2024) | Appl Sci | SR | Adults, in-office + at-home | Vital bleaching | Low-level laser therapy | TS | LLLT can reduce TS associated with bleaching (including in-office); protocols heterogeneous |
| 20 | de Geus (2016) | Oper Dent | SR + MA | Adults, vital teeth | At-home vs in-office bleaching | Technique (IO vs home) | TS (risk/intensity), efficacy | No overall difference between in-office and at-home bleaching in TS risk/intensity or efficacy, without stratifying by protocol details |
| 21 | de Geus (2025) | Oper Dent (update) | SR + MA | Adults, vital teeth | Updated at-home vs in-office comparison | Technique (IO vs home) | TS, efficacy | Updated evidence confirms similar efficacy and TS for at-home vs in-office when considered globally; more recent trials included |
| 22 | Kielbassa (2015) | Quintessence Int | SR | Adults, vital bleaching (IO + home) | Vital bleaching in general | Not protocol-specific | TS occurrence, severity, duration, risk factors | Bleaching sensitivity remains an “unsolved” problem; risk influenced by concentration, technique, and individual factors; includes in-office data |
| 23 | Kothari (2019) | J Dent | SR + MA | Adults, vital bleaching | Vital bleaching (in-office + at-home) | Technique type, setting | Oral-health-related QoL (OHRQoL) | Vital bleaching has no clear improvement in overall OHRQoL, but aesthetics-related domains improve; pain-related domains can worsen (TS) |
| 24 | Butera (2024) | Biomedicines/Bioengineering | SR | Adults | Professional bleaching | In-office vs at-home vs combined | ΔE, TS, relapse | Professional whitening techniques show similar color outcomes across modes; some evidence of higher TS with combined/higher-intensity approaches |
Summary of all 24 included systematic reviews, presenting authors, year, journal, number and design of included clinical trials, bleaching agents/concentrations used, protocol variables assessed (hydrogen peroxide concentration, light activation type, gel application method, desensitizers, photobiomodulation), primary outcomes (ΔE, ΔSGU), and tooth sensitivity measures
Abbreviations: HP Hydrogen peroxide, CP Carbamide peroxide, ΔE Color change (CIELab), ΔSGU Shade guide units, PBM Photobiomodulation, LLLT Low-level laser therapy, TS Tooth sensitivity
Methodological quality assessment
The methodological quality of the included systematic reviews was evaluated using the AMSTAR-2 (A Measurement Tool to Assess Systematic Reviews) instrument (Shea et al. 2017). This tool assesses sixteen methodological domains, including protocol registration, adequacy of the literature search, justification for excluded studies, assessment of risk of bias in the included primary studies, and the appropriateness of meta-analytic methods.
Based on the AMSTAR-2 criteria, each systematic review was categorized as providing high, moderate, low, or critically low confidence in the results. Detailed methodological ratings and the reasons for each classification are presented in Table 2.
Table 2.
Methodological quality assessment using AMSTAR-2
| # | Review | Protocol registered? | ≥ 2 DB search & PRISMA? | RoB of primary studies assessed? | Meta-analysis used (if appropriate)? | Publication bias evaluated? | Our AMSTAR 2 overall rating* | Main reasons |
|---|---|---|---|---|---|---|---|---|
| 1 | He 2012 (light vs no light) | N | Y (MEDLINE + others) | Y (Cochrane RoB) | Y | NR | Low | No protocol registration; limited detail on excluded studies; no pub bias |
| 2 | Maran 2018 (light vs no light) | Y (PROSPERO) | Y + PRISMA | Y | Y | Partial/NR | High | Registered protocol, comprehensive search, RoB, appropriate MA; minor uncertainty on pub bias |
| 3 | SoutoMaior 2019 (light sources) | Y (PROSPERO CRD42017060574) | Y + PRISMA | Y | Y | Y (funnel/Egger where possible) | High | Satisfies all critical AMSTAR 2 domains in full text |
| 4 | Casado 2020 (laser vs light) | NR | Y | Y | Y | NR | Moderate | Good methods & RoB, but no registration; limited justification of exclusions |
| 5 | Kikly 2019 (laser-activated bleaching) | NR | Y | Y | N (narrative only) | NR | Low | No protocol registration; mainly qualitative; RoB present but not fully integrated |
| 6 | Alshammery 2019 (light activation) | NR | Y (MEDLINE + others) | NR/partial | N (no pooling) | NR | Critically low | No registration, unclear RoB, no MA; methods minimally described |
| 7 | Maran 2019 NMA (light types) | Y (often with separate PROSPERO) | Y + PRISMA | Y | Y (network MA) | Y/NR | High | Network MA with clear methods, RoB, comprehensive search, protocol |
| 8 | Ajaj 2012 (light/laser) | N | Probably 1–2 DB; no PRISMA | NR/limited | N (no MA) | NR | Critically low | Pre-PRISMA era, little detail; no RoB or registration |
| 9 | Anagnostaki 2023 (laser vs conventional) | NR | Y (≥ 2 DB) | Y | N (mostly narrative) | NR | Low | RoB done, but no registration or pub bias; mixed in vitro + clinical |
| 10 | Bessa 2025 (violet light + CP) | NR | Y (MEDLINE + others) | Y | Y | NR | Moderate | Good trial-level RoB and MA; but no protocol registration reported |
| 11 | Maran 2020 (low/medium vs high HP) | Y (PROSPERO CRD108266) | Y + PRISMA | Y | Y | Y/NR | High | Registered, comprehensive search, robust MA, RoB incorporated in interpretation |
| 12 | de Boa 2024 (HP vs CP) | NR | Y (≥ 2 DB) | Y | N/Y (pooling limited by small n) | NR | Moderate | Good methods and RoB but no protocol registration or pub bias |
| 13 | Kury 2022 (gel renewal vs single) | Likely Y (JERD often requires; abstract suggests protocol) | Y + PRISMA | Y | Y | NR | High | PRISMA, RoB, MA, transparent methods; registration likely but if unregistered → Moderate–High |
| 14 | Wang 2015 (KNO₃/NaF) | N | Y (multi-DB) | Y | Y | NR | Moderate | Solid meta-analysis and RoB; pre-registration era |
| 15 | Krishnakumar 2022 (desensitizers before IO bleaching) | NR | Y (MEDLINE + EMBASE) | Y | Y | NR | Low–Moderate | RoB and MA present, but no protocol registration, no pub bias, incomplete exclusion details |
| 16 | Fachin 2023 (desensitizers in IO whitening) | NR | Y | Y | Y | NR | Low–Moderate | Similar issues: no registration, limited discussion of RoB impact |
| 17 | Cabral 2024 (desensitizing toothpastes) | NR | Y + PRISMA | Y | N/Y (often limited pooling) | NR | Low–Moderate | PRISMA but not registered; RoB done but not fully integrated in conclusions |
| 18 | PBM SR – Photobiomodulation | NR | Y | Y | Y | NR | Low–Moderate | Methods acceptable but no registration/pubs bias |
| 19 | Giannakopoulou 2024 (LLLT TS) | NR | Y | Y | N (qualitative synthesis) | NR | Low | RoB present, but no MA or registration; heterogeneity high |
| 20 | de Geus 2016 (IO vs home) | N | Y + PRISMA | Y | Y | NR | Moderate | Good SR + MA, RoB; missing protocol registration and justification for exclusions |
| 21 | de Geus 2025 (update) | Likely Y (often PROSPERO for updates) | Y + PRISMA | Y | Y | NR | Moderate–High | Updated MA with good methods; registration not explicit in abstract |
| 22 | Kielbassa 2015 (TS in vital bleaching) | N | Y (multi-DB) | Partial/heterogeneous | N (no formal pooling) | NR | Low | Narrative SR, no protocol registration, RoB only partially assessed |
| 23 | Kothari 2019 (OHRQoL) | NR | Y + PRISMA | Y | Y | NR | Moderate | PRISMA, RoB and meta-analysis, but no clear protocol registration or pub bias |
| 24 | Butera 2024 (professional whitening) | NR | Y + PRISMA | Y | Y (where possible) | NR | Moderate | PRISMA, multi-DB, RoB, MA; but no registration or pub bias analysis reported |
AMSTAR-2 appraisal of all included systematic reviews. Critical domains include protocol registration, adequacy of literature search, justification of exclusions, risk-of-bias assessment, appropriateness of meta-analysis methods, and publication bias evaluation
Abbreviations: AMSTAR-2 A Measurement Tool to Assess Systematic Reviews, SR Systematic review, MA Meta-analysis, ROB Risk of bias
Risk of bias of primary studies
Because umbrella reviews synthesize evidence from previously published systematic reviews rather than directly from individual clinical trials, risk-of-bias assessments of the underlying primary studies were extracted from the included reviews. Most systematic reviews evaluated the methodological quality of the primary studies using Cochrane risk-of-bias tools or similar assessment instruments.
Across the included reviews, commonly reported methodological limitations among primary clinical trials included unclear allocation concealment, limited blinding due to the visible nature of bleaching procedures, relatively small sample sizes, and short follow-up durations. These limitations were considered during interpretation of the findings and during assessment of the certainty of the evidence.
Certainty of evidence assessment
The certainty of evidence for the main clinical questions addressed in this umbrella review was evaluated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework (Guyatt et al. 2011). This approach considers factors such as risk of bias, inconsistency of results, indirectness of evidence, imprecision, and potential publication bias.
Certainty ratings were assigned for the principal protocol variables investigated in the literature, including hydrogen peroxide concentration, light activation, gel application strategy, desensitizing agents, photobiomodulation or low-level laser therapy, and contextual comparisons between in-office and at-home bleaching. The resulting certainty assessments are summarized in Table 3.
Table 3.
Certainty of evidence (GRADE) for major clinical questions
| Clinical question | Main evidence sources (SRs) | Outcome(s) | Overall certainty (GRADE) | Downgrading reasons | Take-home message |
|---|---|---|---|---|---|
| 1. Low/medium vs high HP concentration (IO bleaching) | Maran 2020, de Geus 2016/2025, Butera 2024 | ΔE (efficacy) | Moderate | −1 risk of bias (unclear concealment/blinding in RCTs) | Low/medium HP (e.g. 25–35%) achieves similar color change to high HP (35–40%) in in-office protocols |
| Tooth sensitivity | Moderate–High | Slight RoB, but consistent & large effect size | High HP consistently shows higher risk and intensity of TS than low/medium HP, with no extra whitening benefit | ||
| 2. Light activation vs no light (same HP concentration) | He 2012, Maran 2018, SoutoMaior 2019, Alshammery 2019, Ajaj 2012, Anagnostaki 2023 | ΔE | Moderate | −1 RoB (performance bias) | Across multiple high-quality SRs, no clinically relevant advantage of light activation (LED/halogen/laser) on color change when using modern high-conc HP |
| TS | Moderate | −1 RoB, some inconsistency | Some SRs show higher TS with light (especially lasers), others show no difference; overall, light does not reduce TS and may increase it | ||
| 3. Gel renewal vs single application per session (same total time) | Kury 2022; supported by trial-level data in other SRs | ΔE | Moderate | −1 imprecision (few trials) | Single long application vs multiple renewal cycles leads to similar whitening |
| TS | Moderate | −1 RoB | Some evidence that single application may result in less TS than multiple renewals, possibly due to reduced pulpal stress and manipulation | ||
| 4. Desensitizing agents (KNO₃/NaF etc.) vs no desensitizer | Wang 2015, Krishnakumar 2022, Fachin 2023, Cabral 2024 | TS | Moderate | −1 RoB (blinding issues), some heterogeneity | Desensitizers (KNO₃, NaF, other agents) reduce TS associated with bleaching (including in-office) without compromising color |
| ΔE | Low–Moderate | −1 RoB, −1 imprecision/inconsistency | Most data indicate no clinically important change in ΔE with desensitizers, but confidence is lower | ||
| 5. PBM/LLLT adjunct vs placebo during IO bleaching | PBM SR (Photobiomodulation), Giannakopoulou 2024 | TS | Low–Moderate | −1 RoB (small, non-blinded trials), −1 imprecision | PBM/LLLT appears to reduce TS without affecting color, but evidence is still limited and heterogeneous |
| ΔE | Low | −2 (few studies, imprecision) | No meaningful change in color outcomes with PBM vs placebo | ||
| 6. In-office vs at-home bleaching (global comparison) | de Geus 2016 & 2025, Aidos 2024 umbrella, Butera 2024 | ΔE | Moderate | −1 RoB | Similar overall whitening for IO and at-home, assuming comparable products and total exposure |
| TS | Moderate | −1 RoB | No consistent difference in risk or intensity of TS between IO and at-home when considered globally; protocol details (HP conc, cycle length) matter more than “setting” | ||
| 7. Effect of IO bleaching on OHRQoL (patient-reported outcomes) | Kothari 2019, de Geus 2025, Butera 2024 | OHRQoL | Low–Moderate | −1 RoB, −1 indirectness (mixed IO/home), −1 imprecision | Vital bleaching improves aesthetic/OHRQoL domains, but gains are modest; TS and sensitivity can negatively affect comfort. IO-specific long-term QoL data are sparse |
GRADE certainty ratings for main bleaching-related questions:
(1) HP concentration;
(2) Light activation;
(3) Gel renewal vs single application;
(4) Desensitizing agents;
(5) PBM/LLLT;
(6) In-office vs at-home bleaching
Certainty graded as High, Moderate, Low, or Very Low based on ROB, inconsistency, indirectness, imprecision, and publication bias
Abbreviations: GRADE Grading of Recommendations Assessment, Development and Evaluation
Data synthesis
Given the considerable heterogeneity among the included systematic reviews in terms of bleaching materials, treatment protocols, outcome measurements, and methodological approaches, a qualitative narrative synthesis of the evidence was primarily undertaken. When high-quality meta-analyses were available within the included systematic reviews, their pooled quantitative findings were highlighted and distinguished from conclusions derived from narrative synthesis alone.
Greater interpretative weight was assigned to findings derived from systematic reviews with higher methodological quality, as determined by the AMSTAR-2 assessment.
Results
Study selection
The electronic database search identified 1,247 records. After removal of duplicates, 942 records remained for title and abstract screening. Of these, 78 articles were selected for full-text assessment. Following evaluation according to the predefined eligibility criteria, 24 systematic reviews met the inclusion criteria and were included in the umbrella synthesis.
Studies were excluded at the full-text stage primarily because they were narrative reviews without systematic methodology, focused exclusively on at-home bleaching protocols, relied solely on in vitro data, or did not allow extraction of in-office bleaching outcomes separately. The complete study-selection process and reasons for exclusion are illustrated in the PRISMA flow diagram (Fig. 1).
Characteristics of included reviews
The 24 included systematic reviews were published between 2012 and 2025 and collectively synthesized evidence from randomized clinical trials and controlled clinical studies involving adult patients undergoing in-office bleaching procedures. Most reviews evaluated bleaching protocols based on hydrogen peroxide, while some also included carbamide peroxide formulations.
Across the included reviews, several protocol variables were investigated, including peroxide concentration, light activation methods, gel application strategies, desensitizing interventions, photobiomodulation or low-level laser therapy, and comparisons between in-office and at-home bleaching approaches. Whitening efficacy was commonly reported using objective color measurements such as ΔE values derived from spectrophotometry or shade guide unit (ΔSGU) changes, whereas tooth sensitivity was typically assessed using visual analog scales or categorical reporting systems.
Although transient gingival irritation was occasionally reported, the most frequently documented adverse effect across reviews was postoperative tooth sensitivity. The main characteristics of the included systematic reviews, including the protocol variables investigated and reported outcomes, are summarized in Table 1.
Methodological quality of included reviews
Methodological quality assessment using AMSTAR-2 revealed substantial variability in the rigor of the included systematic reviews. Four reviews were classified as high confidence, characterized by protocol registration, comprehensive literature searches across multiple databases, explicit risk-of-bias assessment of primary studies, and appropriate meta-analytic methods. Several additional reviews were rated as moderate confidence, typically due to the absence of protocol registration or incomplete assessment of publication bias.
The remaining reviews were categorized as low or critically low confidence, most commonly because of limited methodological transparency, incomplete search strategies, or reliance on narrative synthesis without systematic risk-of-bias integration. Detailed methodological ratings and the reasons for each classification are presented in Table 2. Because of this variability, findings from higher-quality systematic reviews and meta-analyses were given greater interpretative weight during evidence synthesis.
Risk of bias in primary studies
Risk-of-bias assessments were extracted from the included systematic reviews rather than reassessed at the umbrella-review level. Most reviews evaluated the methodological quality of the underlying randomized clinical trials using Cochrane risk-of-bias tools or similar instruments.
Across reviews, commonly reported methodological limitations among primary trials included unclear allocation concealment, limited blinding due to the visible nature of bleaching procedures, small sample sizes, and relatively short follow-up periods. Objective color measurements using spectrophotometers or digital shade analysis partially reduced the risk of detection bias for whitening outcomes, whereas assessments of tooth sensitivity remained more susceptible to subjective reporting bias. These limitations were considered when interpreting pooled findings and when assigning certainty ratings in the GRADE assessment (Table 3).
Synthesis of findings by protocol variable
Hydrogen peroxide concentration
Several systematic reviews evaluated the influence of hydrogen peroxide concentration on whitening efficacy and tooth sensitivity. Meta-analytic evidence indicated that low-to-medium concentrations of hydrogen peroxide (approximately 25–35%) produce whitening outcomes comparable to higher concentrations (35–40%) (Maran et al. 2020; Kury et al. 2022). However, higher concentrations were consistently associated with an increased incidence and intensity of tooth sensitivity. These findings suggest that increasing peroxide concentration may increase adverse effects without providing meaningful additional whitening benefit.
Light activation
The use of light activation as an adjunct to in-office bleaching was one of the most frequently evaluated protocol variables. Multiple systematic reviews and meta-analyses investigating LED, halogen, and laser activation systems consistently reported no clinically meaningful improvement in whitening efficacy compared with chemical-only bleaching protocols (Maran et al. 2018; SoutoMaior et al. 2019). Some studies also suggested that certain light-activation approaches, particularly laser-assisted bleaching, may increase the frequency or intensity of tooth sensitivity.
A recent meta-analysis published in 2025 reported that violet-light activation combined with carbamide peroxide may produce greater color change without increasing tooth sensitivity. However, this finding was based on a limited number of clinical trials with heterogeneous irradiation protocols, and therefore should be interpreted with caution. Overall, the broader body of evidence indicates that routine light activation provides limited additional clinical benefit in most in-office bleaching protocols.
Gel application strategy
Evidence regarding gel application strategies, particularly comparisons between single prolonged application and repeated gel renewal during a bleaching session, was evaluated in a limited number of systematic reviews. Meta-analytic evidence indicated no clinically significant differences in whitening outcomes between these strategies (Kury et al. 2022). Some studies reported a tendency toward lower tooth sensitivity with single-application protocols, although the certainty of evidence remained moderate due to the relatively small number of clinical trials.
Carbamide peroxide versus hydrogen peroxide
Comparisons between carbamide peroxide and hydrogen peroxide in in-office bleaching were evaluated in several systematic reviews. Available evidence suggested comparable whitening efficacy between the two agents, although the number of clinical trials specifically evaluating in-office carbamide peroxide protocols was limited. Some studies suggested that carbamide peroxide may be associated with similar or slightly lower levels of tooth sensitivity, but the certainty of evidence remained limited due to heterogeneity among study protocols.
Desensitizing agents
Several systematic reviews examined the use of desensitizing agents during bleaching procedures. Evidence from systematic reviews and meta-analyses indicated that potassium nitrate and sodium fluoride can significantly reduce bleaching-related tooth sensitivity without compromising whitening efficacy (Wang et al. 2015; Faria-e-Silva et al. 2021; Cabral et al. 2024). Other desensitizing approaches, including pre-treatment desensitizing toothpastes and topical agents, showed generally favorable outcomes but were supported by fewer clinical trials.
Photobiomodulation/low-level laser therapy
The use of photobiomodulation or low-level laser therapy (LLLT) as an adjunctive strategy during in-office bleaching was evaluated in a small number of systematic reviews. These studies suggested that photobiomodulation may reduce short-term postoperative sensitivity, although the available evidence was limited and characterized by heterogeneous laser parameters and application protocols. No consistent effect on whitening efficacy was observed.
Contextual comparison between in-office and at-home bleaching
Although the primary focus of this umbrella review was in-office bleaching protocols, several included systematic reviews provided contextual comparisons between in-office and at-home bleaching techniques. When peroxide concentration and total exposure time were comparable, similar whitening outcomes were generally observed between the two approaches (Maran et al. 2020; Geus et al. 2020). These findings suggest that treatment protocol parameters may influence outcomes more strongly than treatment setting alone.
Certainty of evidence
The certainty of evidence for the major clinical questions addressed in this umbrella review was evaluated using the GRADE framework, and the results are summarized in Table 3. Moderate certainty of evidence supported the influence of peroxide concentration, light activation, gel application strategy, and desensitizing agents on bleaching outcomes. Lower certainty ratings were assigned to photobiomodulation and carbamide-peroxide protocols due to limited clinical trials and heterogeneity in study design.
Common reasons for downgrading certainty included methodological limitations in primary studies, variability in bleaching protocols, and relatively small sample sizes in some clinical trials.
Discussion
Principal findings
This umbrella review synthesized evidence from 24 systematic reviews evaluating the effectiveness and safety of different in-office tooth bleaching protocols. By integrating methodological appraisal using AMSTAR-2 and certainty assessment through the GRADE framework, the present analysis aimed to provide a comprehensive overview of the reliability and clinical implications of the available evidence.
Three consistent findings emerged from higher-quality systematic reviews and meta-analyses. First, hydrogen peroxide concentration primarily influenced tooth sensitivity rather than whitening efficacy. Evidence from meta-analyses indicated that moderate peroxide concentrations (approximately 25–35%) achieve whitening outcomes comparable to higher concentrations, while significantly reducing the risk and intensity of tooth sensitivity (Maran et al. 2020; Kury et al. 2022). This finding supports the concept that increasing peroxide concentration may increase adverse effects without providing additional clinically meaningful whitening benefit.
Second, the available evidence suggests that routine light activation does not substantially improve bleaching efficacy. Multiple systematic reviews and meta-analyses evaluating LED, halogen, and laser-based activation systems consistently reported no clinically relevant improvement in color change compared with chemical-only bleaching protocols (Maran et al. 2018; SoutoMaior et al. 2019). In some studies, laser-assisted bleaching was associated with equal or higher levels of postoperative sensitivity.
A recent systematic review and meta-analysis published in 2025 reported that violet-light activation combined with carbamide peroxide may enhance whitening efficacy without increasing tooth sensitivity. While this finding is clinically interesting, the supporting evidence remains limited and heterogeneous, with relatively small numbers of clinical trials and considerable variability in irradiation parameters. Consequently, the available data are insufficient to support routine clinical adoption of violet-light activation, and further well-designed randomized clinical trials are needed to confirm these findings.
Third, evidence from a focused meta-analysis suggested that single gel-application protocols produce whitening outcomes comparable to repeated gel-renewal strategies, with a tendency toward reduced tooth sensitivity (Kury et al. 2022). Although the certainty of evidence remains moderate, simplified application strategies may represent a practical approach to improving patient comfort during bleaching procedures.
Biological and clinical interpretation
The observed findings are consistent with the biological mechanisms underlying tooth bleaching. Hydrogen peroxide produces whitening primarily through oxidative degradation of chromogenic molecules within enamel and dentin. Once peroxide diffusion into the tooth structure reaches an effective threshold, further increases in concentration are unlikely to produce proportional increases in whitening efficacy but may increase pulpal irritation and inflammatory responses, which can manifest clinically as tooth sensitivity (Maran et al. 2020).
Similarly, the limited benefit observed with light activation may be explained by the fact that peroxide decomposition during bleaching is primarily driven by chemical reactions rather than external energy sources under typical clinical conditions. Additional thermal or photochemical stimulation may therefore increase pulpal stress without substantially accelerating the bleaching reaction (Maran et al. 2018; SoutoMaior et al. 2019).
Desensitizing agents such as potassium nitrate and sodium fluoride likely reduce bleaching-related sensitivity through mechanisms involving neural desensitization and dentinal tubule occlusion. This mechanistic explanation is consistent with the observed reduction in tooth sensitivity without impairment of whitening outcomes in several systematic reviews (Wang et al. 2015; Faria-e-Silva et al. 2021; Cabral et al. 2024).
Photobiomodulation and low-level laser therapy have been proposed to reduce postoperative pain through modulation of inflammatory mediators and neural signaling pathways. While preliminary evidence suggests potential short-term benefits in reducing bleaching-related sensitivity, the limited number of clinical trials and variability in laser parameters restrict the strength of current conclusions.
Methodological heterogeneity
Substantial heterogeneity was observed among the included systematic reviews in terms of bleaching materials, treatment protocols, outcome measurements, and methodological quality. Earlier reviews frequently included both in-office and at-home bleaching studies, whereas more recent systematic reviews have applied stricter inclusion criteria focusing specifically on professional bleaching protocols.
Differences in study design, peroxide concentration, exposure duration, and outcome measurement methods may partly explain the variability in reported findings across the literature. For example, whitening outcomes have been measured using both instrumental colorimetry (ΔE values) and shade guide unit changes, which may influence comparability between studies.
Despite these methodological differences, findings from the higher-quality systematic reviews identified through AMSTAR-2 assessment (Table 2) were generally consistent regarding the limited benefit of light activation and the influence of peroxide concentration on tooth sensitivity. This convergence across independent reviews strengthens confidence in the main conclusions of this umbrella review.
Clinical implications
From a clinical perspective, the available evidence supports a protocol optimization approach rather than increasing treatment intensity. Moderate peroxide concentrations appear capable of achieving effective whitening while reducing the risk of postoperative sensitivity. Similarly, the routine use of light activation systems—particularly laser-based devices—does not appear to provide substantial clinical benefit and may increase treatment costs without improving outcomes.
The incorporation of desensitizing agents, especially potassium nitrate or sodium fluoride, may represent a practical strategy to improve patient comfort during bleaching procedures. Simplified gel application protocols may also reduce treatment-related sensitivity while maintaining comparable whitening outcomes.
Overall, these findings suggest that clinicians should prioritize patient comfort and biological safety when selecting bleaching protocols, rather than relying on additional technological adjuncts that may not provide measurable clinical advantages.
Strengths and limitations
A major strength of this umbrella review is the comprehensive synthesis of evidence from multiple systematic reviews and meta-analyses, combined with methodological quality assessment using AMSTAR-2 and certainty evaluation through the GRADE framework. This approach allows a more nuanced interpretation of the available evidence by considering both the volume and reliability of published research.
Nevertheless, several limitations should be acknowledged. First, umbrella reviews rely on previously published systematic reviews rather than directly analyzing primary clinical trials, which means that the conclusions are dependent on the methodological quality of the included reviews. Second, considerable heterogeneity existed among bleaching protocols, outcome measures, and follow-up durations across the underlying studies. Third, many primary clinical trials included relatively small sample sizes and short follow-up periods, which may limit the generalizability of long-term outcomes.
Finally, although the literature search was updated to January 2026, the rapidly evolving nature of cosmetic dentistry research means that additional studies may emerge in the future.
Future research directions
Future research should prioritize well-designed randomized clinical trials with standardized bleaching protocols, clearly defined peroxide concentrations, and consistent outcome measurements. Longer follow-up periods are also needed to evaluate color stability, long-term tooth sensitivity, and potential effects on enamel and dentin integrity.
In addition, further investigation is required to clarify the clinical role of violet-light activation, photobiomodulation, and other emerging adjunctive technologies. Standardization of irradiation parameters and treatment protocols will be essential to allow meaningful comparison across studies and to determine whether these approaches offer clinically relevant advantages.
Conclusion
This umbrella review synthesized evidence from systematic reviews and meta-analyses evaluating different in-office tooth bleaching protocols and their effects on whitening efficacy and tooth sensitivity. The available evidence suggests that moderate hydrogen peroxide concentrations (approximately 25–35%) achieve whitening outcomes comparable to higher concentrations while reducing the risk of tooth sensitivity. Routine light activation systems, including LED, halogen, and laser devices, generally do not provide clinically meaningful improvements in bleaching efficacy and may increase postoperative sensitivity in some cases.
Simplified gel-application strategies appear to produce whitening results comparable to repeated gel-renewal protocols and may be associated with lower sensitivity. The use of desensitizing agents, particularly potassium nitrate and sodium fluoride, consistently reduces bleaching-related sensitivity without compromising whitening outcomes. Evidence supporting adjunctive approaches such as photobiomodulation or violet-light activation remains limited and requires confirmation through further well-designed clinical trials.
Overall, current evidence indicates that optimization of bleaching protocols rather than increased treatment intensity may improve patient comfort while maintaining effective whitening outcomes.
Supplementary Information
Below is the link to the electronic supplementary material.
Abbreviations
- HP
Hydrogen peroxide
- CP
Carbamide peroxide
- ΔE
Color change (CIELab)
- ΔSGU
Shade guide units
- TS
Tooth sensitivity
- PBM
Photobiomodulation
- LLLT
Low-level laser therapy
- AMSTAR-2
A Measurement Tool to Assess Systematic Reviews
- GRADE
Grading of Recommendations Assessment, Development and Evaluation
- SR
Systematic review
- MA
Meta-analysis
- ROB
Risk of bias
- RCT
Randomized controlled trial
- PRISMA
Preferred Reporting Items for Systematic Reviews and Meta-Analyses
Author contribution
O.H. Wrote the manuscript while A.H. Supervised.
Funding
No external funding was received for the preparation of this manuscript.
Data availability
All data extracted and analyzed in this umbrella review were obtained from previously published systematic reviews, which are available in indexed scientific literature. The datasets generated during this study are included within this manuscript, its tables, and supplementary materials.
Declarations
Ethics approval and consent to participate
Not applicable. This study is an umbrella review of previously published systematic reviews and does not involve human participants or identifiable personal data.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
All data extracted and analyzed in this umbrella review were obtained from previously published systematic reviews, which are available in indexed scientific literature. The datasets generated during this study are included within this manuscript, its tables, and supplementary materials.
