Abstract
Background
Locally delivered curcumin and turmeric-derived formulations have been proposed as adjuncts to scaling and root planing (SRP), but the evidence is difficult to interpret because trials differ by design, comparator, population, formulation and follow-up.
Methods
We searched PubMed, Embase, Scopus, Web of Science, CENTRAL, ClinicalTrials.gov, and other relevant sources from inception to 18 May 2026. Search terms covered curcumin, turmeric, curcuminoids, Curcuma longa, periodontitis, periodontal pockets, scaling and root planing, non-surgical periodontal therapy, and local or subgingival drug delivery. Two reviewers independently screened records, extracted data and assessed risk of bias using RoB 2. Random-effects meta-analyses were stratified by study design, comparator type and population, and certainty of evidence for the primary outcome was assessed using GRADE.
Results
The search identified 71 database records and 8 ClinicalTrials.gov registry records. Twenty-nine randomized or quasi-randomized clinical reports were included in the qualitative synthesis, and 27 reports contributed extractable PPD data to at least one quantitative analysis. In systemically healthy participants with inactive controls, adjunctive curcumin/turmeric-derived delivery was associated with modest PPD reduction in parallel-arm studies (6 studies; MD -0.67 mm, 95% CI -1.13 to -0.22; I2 = 79.6%) and split-mouth studies (15 studies; MD -0.46 mm, 95% CI -0.68 to -0.24; I2 = 87.5%). Prediction intervals crossed the null in both analyses, and the certainty of evidence for PPD reduction was rated as low because of risk of bias and inconsistency. Active-comparator analyses were highly heterogeneous and exploratory.
Conclusions
Locally delivered curcumin/turmeric-derived formulations used adjunctively with SRP may provide a modest improvement in PPD reduction; however, the findings should be interpreted cautiously because of substantial heterogeneity and methodological limitations. The certainty and clinical applicability of the evidence remain limited by small trials, high heterogeneity, incomplete reporting, variable formulations and geographically clustered evidence. Current evidence does not establish dose-response, formulation superiority, safety, or replacement of chlorhexidine, antibiotics or other conventional antimicrobial agents.
Registration
PROSPERO CRD420261333717, Registered on 6 March 2026
Supplementary Information
The online version contains supplementary material available at 10.1186/s12903-026-08846-x.
Keywords: curcumin, turmeric, periodontitis, scaling and root planing, local drug delivery, systematic review, meta-analysis
Introduction
Periodontitis is a chronic inflammatory disease in which dysbiotic biofilms and host immune responses drive clinical attachment loss and alveolar bone resorption [1, 2]. Scaling and root planing remains the foundation of non-surgical periodontal therapy, but residual pockets, furcation anatomy and root concavities can limit mechanical debridement and favour microbial recolonization [3–5]. Local drug-delivery systems have therefore been evaluated to increase therapeutic exposure within periodontal pockets while limiting systemic exposure [6, 7].
Curcumin, turmeric and Curcuma longa-derived preparations are biologically plausible adjuncts because they combine antimicrobial, antioxidant and anti-inflammatory activities. Experimental studies suggest effects on NF-κB signalling, inflammatory cytokines, oxidative stress and periodontopathic bacteria [8–14]. These mechanisms align with the microbial and host-response components of periodontitis, but mechanistic plausibility does not establish a clinically meaningful effect in heterogeneous clinical trials.
Previous systematic reviews and meta-analyses have examined curcumin or turmeric-based adjuncts in non-surgical periodontal therapy, but several issues continue to limit clinical interpretation, including outdated search windows, narrow search terminology, small trials, mixed comparator types, inconsistent handling of split-mouth designs, variable formulations and concentrations, and limited attention to special populations. The present review was designed to address these limitations by updating the search to 18 May 2026, broadening the search strategy to include turmeric-derived and subgingival local-delivery terminology, explicitly searching ClinicalTrials.gov, and stratifying analyses by study design, comparator type and population. Formulation, concentration and follow-up findings were treated as exploratory sources of heterogeneity rather than confirmatory evidence of dose-response or formulation superiority.
Methods
Protocol and registration
This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement [15] and was registered in PROSPERO (registration number: CRD420261333717, registered on 6 March 2026).
Search strategy and trial-register search
We searched PubMed, Embase, Web of Science, the Cochrane Library and Scopus from inception to 18 May 2026. The final strategy combined intervention terms (curcumin, turmeric, curcuminoids, Curcuma longa), condition terms (periodontitis, periodontal disease, periodontal pocket), treatment-context terms (scaling and root planing, root planing, periodontal debridement, non-surgical periodontal therapy), and delivery-route terms (local drug delivery, subgingival delivery, subgingival application). Full strategies are provided in the Supplementary Information.
ClinicalTrials.gov was searched up to 18 May 2026 using curcumin/turmeric and periodontitis/periodontal-disease terms. Registry records were used to identify ongoing, unpublished or linked published trials. Registry records without posted results or linked full-text publications were removed once before title/abstract screening and were not repeated as full-text exclusions. Reference lists of included studies and previous systematic reviews were also screened [16–19].
Eligibility criteria
Eligible studies were randomized or quasi-randomized controlled clinical trials, including parallel-arm and split-mouth designs, in patients with periodontitis, including studies using the term chronic periodontitis under older classifications. For split-mouth studies, random or quasi-random allocation of sites, quadrants or periodontal pockets was required. Interventions were subgingivally delivered curcumin, turmeric, Curcuma longa or curcuminoid formulations used adjunctively with SRP. Eligible local-delivery vehicles included gels, chips, strips, in situ systems, nanoparticles or comparable subgingival delivery systems. Controls were categorized as inactive controls, including SRP alone, placebo or empty vehicle, or active comparators such as chlorhexidine, ornidazole, neem or other adjunctive local agents. Eligible studies were required to report at least one clinical periodontal outcome, including PPD, CAL, plaque index, gingival index or bleeding outcomes, with a minimum follow-up of 21 days.
Studies were excluded if they evaluated mouthwash, systemic administration, photodynamic therapy as the curcumin mechanism, animal or in-vitro experiments, or non-subgingival delivery. Additional exclusions were applied to studies with non-random or fixed allocation, unclear allocation without evidence of random or quasi-random assignment, duplicate or overlapping populations, or reports without extractable clinical outcomes. Randomized or quasi-randomized reports with relevant clinical content but incompatible variance information were retained in the qualitative synthesis but excluded from meta-analysis. Trial registry records without posted results or linked full-text publications were handled during record screening and were not counted as full-text exclusions.
Analytical grouping framework
Analyses were grouped according to the clinical question being estimated. The main clinical comparison was adjunctive benefit over an inactive control, defined as locally delivered curcumin/turmeric-derived formulation plus SRP versus SRP alone, placebo or empty vehicle. Active-comparator trials estimated a different question—comparative performance against another local agent or adjunctive modality—and were analysed separately as exploratory evidence.Parallel-arm and split-mouth trials were not pooled together because split-mouth designs are within-patient comparisons and require paired-analysis assumptions [20]. For split-mouth trials, inclusion in quantitative synthesis required random allocation of sites, quadrants or periodontal pockets using a reported random allocation method, such as computer-generated randomization, coin toss, lottery method or a comparable procedure. Studies using fixed allocation by arch or site, non-random allocation, or unclear allocation without evidence of random assignment were excluded from the RCT synthesis.
The primary estimates were restricted to systemically healthy participants with inactive controls. Trials in smokers or patients with diabetes were treated as special-population sensitivity evidence because smoking and diabetes can alter inflammation, microbial ecology, wound healing and periodontal response. Whole-turmeric gel, turmeric-chip, Curenext and other turmeric-derived formulations were eligible when the intervention was delivered subgingivally, used adjunctively with SRP, and the allocation method and comparator matched the relevant analysis. Companion or potentially overlapping reports were not double-counted.
Data extraction and risk of bias
Two reviewers independently extracted study characteristics, design, population, allocation method, intervention, comparator, follow-up, PPD, CAL, plaque index, gingival index, bleeding outcomes, adverse events and data format. The primary outcome was PPD at the longest available follow-up. Mean differences were calculated as intervention minus control; negative values favoured curcumin/turmeric adjunctive therapy. For split-mouth studies, paired effect estimates and corresponding standard errors were used when available. When paired standard errors were not reported, standard errors were approximated using an assumed within-patient correlation coefficient of 0.5 and interpreted cautiously.
Risk of bias was assessed using RoB 2 for the primary outcome, PPD reduction, at the longest available follow-up [21]. RoB 2 was applied only to studies meeting the randomized-trial eligibility criteria. The five domains were bias arising from randomization, deviations from intended interventions, missing outcome data, outcome measurement and selective reporting. Insufficiently reported items were judged as some concerns rather than left blank. RoB 2 results were summarized using a weighted domain-level plot in the main text and study-level traffic-light plots in the Supplementary Information.
Statistical analysis
Inverse-variance random-effects meta-analysis was used [22]. Heterogeneity was quantified using I2 and tau2 [23]. Parallel-arm and split-mouth trials were analysed separately. The main quantitative analyses included only randomized or quasi-randomized trials with compatible comparator groups and extractable PPD data. Studies with non-random or fixed allocation, unclear allocation without evidence of random assignment, incompatible variance information, or overlapping populations were not included in pooled estimates.
Because clinical and methodological heterogeneity were expected, prediction intervals were reported for the main analyses to show the range of effects that could plausibly arise in future comparable settings. Funnel plots and small-study-effect assessments were treated as exploratory because trial numbers were small and heterogeneity was high [20, 22–24]. Subgroup and meta-regression findings were interpreted cautiously and were not used as confirmatory evidence of dose-response or formulation superiority.
Certainty of evidence assessment
The certainty of evidence for the primary outcome, probing pocket depth reduction, was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Evidence from randomized or quasi-randomized trials was initially rated as high certainty and was downgraded, when appropriate, for risk of bias, inconsistency, indirectness, imprecision and publication bias. Two reviewers independently performed the assessment, and disagreements were resolved through discussion. Certainty was classified as high, moderate, low or very low. A summary-of-findings table was prepared for the primary PPD analyses and is provided in the Supplementary Information.
Results
Search results and study selection
The database search identified 71 records, and the ClinicalTrials.gov search identified 8 registry records. After removal of 13 duplicates and registry-record handling, 58 records were screened. Twenty records were excluded at title/abstract screening, and 38 full-text clinical reports were assessed for eligibility. Nine reports were excluded after full-text assessment: six evaluated an ineligible route, mechanism or study type, two used non-random or fixed allocation, and one was an overlapping companion report. Overall, 29 reports of randomized or quasi-randomized clinical trials, representing 29 unique studies, were included in the qualitative synthesis. Twenty-seven reports provided extractable PPD data and contributed to at least one quantitative analysis. Registry records were processed before full-text assessment and were not repeated as full-text exclusions. (Fig. 1).
Fig. 1.
PRISMA 2020 flow diagram of study selection
Study characteristics
Eligible reports evaluated subgingivally delivered curcumin, turmeric, Curcuma longa or curcuminoid formulations, including whole-turmeric gel, turmeric-chip, strip, gel, in situ gel, nanoparticle and comparable local-delivery preparations [25–40]. Studies with inactive controls were considered for primary PPD analyses when random or quasi-random allocation and extractable variance information were available [25, 26, 29–32, 35, 36, 41–52]. Studies comparing curcumin/turmeric-derived formulations with chlorhexidine, ornidazole, neem or other active agents were analysed separately as active-comparator evidence [27, 33, 34, 37–39, 53–55]. Randomized reports with clinically relevant content but incompatible PPD variance information, including Anuradha 2015 and Karthickeyan 2019, were retained qualitatively and not pooled [29, 36]. Non-random or fixed-allocation studies and overlapping reports were excluded from the RCT synthesis and documented in the Supplementary Information [56–58].
Risk of bias
For the primary outcome, PPD reduction, most included randomized or quasi-randomized trials were judged as having some concerns in RoB 2. The most frequent reasons were insufficient reporting of allocation concealment, participant or examiner blinding, prespecified analysis plans, outcome assessor calibration and paired-analysis methods for split-mouth designs. Two studies were judged at low risk of bias, and no study was judged at high risk for the primary outcome. Overall, the predominance of some-concerns judgments indicates that the pooled estimates should be interpreted with caution. The weighted domain-level summary is shown in Fig. 2, and the study-level traffic-light plots are provided in Supplementary Figure S2.
Fig. 2.
Weighted summary of RoB 2 judgements for the primary outcome, probing pocket depth reduction, at the longest available follow-up. D1, bias arising from randomization; D2, deviations from intended interventions; D3, missing outcome data; D4, measurement of outcome; D5, selection of reported result
Primary outcome: probing pocket depth
Primary PPD analyses were restricted to randomized or quasi-randomized studies with compatible inactive controls and extractable variance information. In systemically healthy participants, parallel-arm studies showed a pooled MD of -0.67 mm (95% CI -1.13 to -0.22; I2 = 79.6%)(Fig. 3; Table 1). The prediction interval (-2.20 to 0.85 mm) crossed the null, indicating that future comparable settings may show little or no additional benefit despite the average effect favouring adjunctive curcumin/turmeric-derived delivery.
Fig. 3.
Forest plot of PPD reduction in parallel-arm randomized or quasi-randomized studies with inactive controls. Negative values favour adjunctive curcumin/turmeric-derived delivery
Table 1.
Stratified PPD meta-analysis among randomized or quasi-randomized studies with extractable PPD data
| Analysis | Studies | MD (mm) | 95% CI | I2 |
|---|---|---|---|---|
| Parallel healthy inactive RCT/quasi-RCT | 6 | -0.67 | -1.13 to -0.22 | 79.6% |
| Parallel including smokers/diabetes sensitivity | 8 | -0.82 | -1.22 to -0.42 | 83.0% |
| Split-mouth inactive RCT/quasi-RCT | 15 | -0.46 | -0.68 to -0.24 | 87.5% |
| Active comparator exploratory RCT/quasi-RCT | 5 | -0.68 | -1.38 to 0.02 | 98.1% |
Studies with incompatible variance information or ineligible allocation were not included in the primary pooled estimates
The split-mouth inactive-control analysis included 15 randomized or quasi-randomized studies and showed a pooled MD of -0.46 mm (95% CI -0.68 to -0.24; I² = 87.5%)( Fig. 4; Table 1). The prediction interval (-1.32 to 0.40 mm) also crossed the null. These findings support a possible modest average adjunctive effect but do not establish a uniform clinical response.
Fig. 4.
Forest plot of PPD reduction in split-mouth randomized or quasi-randomized studies with inactive controls
When smokers and patients with diabetes were included in a sensitivity analysis of parallel-arm studies, the pooled MD was − 0.82 mm (95% CI -1.22 to -0.42; I² = 83.0%;Table 1). These populations were not allowed to drive the primary estimate because smoking and diabetes may modify host inflammatory response, microbial ecology, wound healing and periodontal outcomes.
Active-comparator analyses were exploratory and highly heterogeneous (5 comparisons; MD -0.68 mm, 95% CI -1.38 to 0.02; I² = 98.1%;Table 1). These results should not be interpreted as evidence that curcumin/turmeric-derived formulations are superior to established agents such as chlorhexidine or ornidazole.
Secondary outcomes, safety and small-study effects
CAL, plaque index, gingival index and bleeding outcomes were summarized conservatively in the Supplementary Information because reporting formats varied across studies, including final scores, change scores, median/range reporting, standard errors, site-level data and incomplete paired variance information. PI, GI and bleeding measures were treated as index scores and were not reported in millimetres. Adverse events were not systematically collected or meta-analysed; therefore, safety cannot be established from this review. Funnel plots and Egger-type tests were considered exploratory because analyses included small studies and high heterogeneity; non-significant tests should not be interpreted as evidence of absence of publication bias.
Certainty of evidence
The certainty of evidence for PPD reduction was rated as low for both parallel-arm and split-mouth inactive-control analyses. The evidence was downgraded mainly because most trials had some concerns in RoB 2 and because substantial heterogeneity remained across studies. Although pooled estimates favoured adjunctive curcumin/turmeric-derived local delivery, prediction intervals crossed the null, indicating uncertainty about the effect expected in future comparable settings. The summary-of-findings table is provided in Supplementary Table S6.
Discussion
This systematic review and meta-analysis provides an updated and clinically stratified synthesis of randomized and quasi-randomized evidence on locally delivered curcumin/turmeric-derived formulations used adjunctively with scaling and root planing for periodontitis. The findings indicate a modest average improvement in probing pocket depth among trials with inactive controls. However, this signal should be interpreted alongside substantial heterogeneity, small trial size, incomplete reporting and prediction intervals crossing the null. The evidence therefore supports a potential adjunctive effect in selected settings, but it does not establish a uniform or predictable clinical response across different periodontal populations, formulations or study designs.
A major contribution of this review is its stricter analytical framework. Previous systematic reviews evaluated curcumin or turmeric-based adjuncts in non-surgical periodontal therapy, including comparisons with SRP alone and with active agents such as chlorhexidine [16–19]. However, clinical interpretation has remained limited by mixed comparator types, inconsistent terminology for curcumin/turmeric-derived products, variable formulations and incomplete separation of parallel-arm and split-mouth designs. The present review addressed these issues by updating the search, broadening intervention and local-delivery terminology, explicitly searching ClinicalTrials.gov, screening reference lists of included studies and previous reviews, excluding non-random or fixed-allocation reports from the RCT synthesis, and stratifying analyses by study design, comparator type and population. The search strategy was intentionally designed to capture not only “curcumin” but also turmeric, curcuminoids, Curcuma longa, periodontal-pocket and subgingival/local-delivery terms, thereby reducing the risk that eligible reports using different intervention terminology would be missed.
The direction of the observed effect is biologically plausible. Periodontitis is driven by dysbiotic microbial biofilms and host-mediated inflammatory tissue destruction [1, 2]. Curcumin has demonstrated anti-inflammatory, antioxidant and antibacterial properties, including effects on inflammatory signalling, oxidative stress and periodontopathic bacteria [8, 9, 12, 13]. Local delivery further provides a rational method for maintaining therapeutic exposure inside periodontal pockets while reducing systemic exposure [6, 7]. Nevertheless, biological plausibility alone cannot confirm clinical effectiveness. Drug retention, release profile, pocket anatomy, SRP quality, baseline disease severity and patient-level risk factors can all determine whether a mechanistic effect translates into measurable periodontal improvement.
Substantial heterogeneity was observed across the main analyses, which is consistent with the clinical and methodological diversity of the included trials [23, 24]. Differences in curcumin/turmeric formulation, concentration, delivery vehicle, follow-up duration, comparator type, baseline pocket depth, examiner calibration, population characteristics and split-mouth variance handling are plausible contributors to variation in treatment effects. Therefore, the pooled estimates should be interpreted as average effects across diverse clinical settings rather than as effects expected uniformly for every patient, periodontal site or formulation. The prediction intervals crossing the null further indicate that the magnitude and direction of benefit may vary in future trials, particularly when formulations, comparators or patient risk profiles differ. These findings support cautious interpretation of the pooled effect and highlight the need for more standardized trial designs.
Study design also influenced the reliability of the evidence. Split-mouth trials are common in periodontal research and can reduce between-patient confounding, but they require random allocation of sites or quadrants and paired statistical handling [20]. Treating fixed-site, fixed-arch or unclear-allocation comparisons as randomized split-mouth trials can underestimate uncertainty and inflate precision. For this reason, reports with non-random allocation, fixed allocation or overlapping populations were excluded from the RCT synthesis. This stricter eligibility decision reduced the number of included reports but strengthened the methodological consistency of the quantitative analysis. It also aligned the evidence base with RoB 2, which is intended for randomized trials [21].
Risk of bias further constrains the certainty of the evidence. Most included trials were judged as having some concerns rather than low risk of bias, largely because allocation concealment, blinding, prespecified analysis plans and paired-analysis methods for split-mouth trials were incompletely reported. In the revised risk-of-bias assessment, incompletely reported domains were classified as “some concerns” rather than left unassessed, and no blank domains were retained in the RoB 2 plots. This approach improves transparency but does not remove the underlying uncertainty. The pooled estimates should therefore be interpreted as provisional and dependent on future trials with clearer randomization, allocation concealment and outcome-assessment procedures.
Comparator type is another important determinant of clinical meaning. Inactive-control trials estimate whether curcumin/turmeric-derived local delivery adds benefit beyond SRP alone, placebo or empty vehicle. Active-comparator trials answer a different question: whether curcumin/turmeric-derived formulations perform differently from another local adjunct such as chlorhexidine, ornidazole or neem. These comparisons should not be merged into a single clinical claim. The active-comparator evidence in this review was highly heterogeneous and exploratory, and it does not demonstrate superiority over established adjunctive agents. Therefore, locally delivered curcumin/turmeric-derived formulations should be interpreted as potential adjuncts to SRP, not as replacements for chlorhexidine, antibiotics or conventional antimicrobial strategies.
Population differences further limit generalization. Trials involving smokers or patients with diabetes were treated as special-population sensitivity evidence because these conditions alter periodontal inflammation, microbial ecology, wound healing and treatment response. This separation was necessary to avoid allowing biologically distinct populations to drive conclusions intended for systemically healthy patients. Geographic clustering also restricts external validity, with many trials conducted in India. Differences in diet, oral microbiome composition, access to periodontal care, SRP delivery standards and background disease risk may influence treatment response. Broader multicentre evidence is needed before the findings can be confidently generalized to diverse clinical populations.
The clinical importance of the observed effect size remains uncertain. A PPD reduction of approximately 0.5–0.8 mm can be meaningful in selected residual or moderate pockets if accompanied by clinical attachment gain, reduced bleeding and long-term stability. However, PPD and CAL are operator-sensitive outcomes influenced by probing force, examiner calibration, inflammation and blinding. Many included trials were small and incompletely reported, and adverse events were not consistently collected or meta-analysed. Consequently, this review cannot support claims of established safety or long-term tolerability. Natural origin should not be equated with safety, and future trials should systematically assess staining, taste alteration, mucosal irritation, allergy, discomfort and other patient-centred outcomes.
Future research should move beyond small proof-of-concept trials toward clinically decisive designs. Trials should be prospectively registered, adequately powered, assessor-blinded and multicentre. Formulations should be standardized, with clear reporting of curcumin concentration, vehicle composition, release characteristics, pocket retention and dosing frequency. Split-mouth studies should report paired estimates and paired variance, while parallel-arm trials should clearly describe randomization, allocation concealment, baseline comparability and blinding. Future analyses should predefine inactive-control and active-comparator questions separately and avoid confirmatory claims about dose-response or formulation superiority unless supported by adequately powered head-to-head data.
In summary, locally delivered curcumin/turmeric-derived formulations used adjunctively with SRP show a modest average association with PPD improvement in selected randomized or quasi-randomized trials. The main scientific value of this review is not only the updated evidence base, but also the stricter separation of study design, comparator type and population, which provides a more clinically interpretable estimate of effect. Current evidence supports continued development and testing of standardized curcumin/turmeric-derived local-delivery systems, but it does not justify routine clinical recommendations or replacement of established periodontal adjuncts. Larger, well-reported randomized trials are required to determine which formulations, patient groups and periodontal conditions are most likely to benefit.
Conclusions
Locally delivered curcumin/turmeric-derived formulations used adjunctively with SRP may provide a modest PPD benefit in selected randomized or quasi-randomized trials. However, the evidence remains limited by high heterogeneity, small sample sizes, incomplete reporting, variable formulations and limited safety data. Current evidence does not establish dose-response, formulation superiority, safety, or replacement of established periodontal adjuncts. Larger, adequately powered and well-reported randomized trials are needed before routine clinical recommendations can be made.
Supplementary Information
Acknowledgements
Not applicable.
Clinical trial number
not applicable
Abbreviations
- CAL
Clinical Attachment Level
- CI
Confidence Interval
- df
Degrees of freedom
- GI
Gingival Index
- MD
Mean Difference
- PI
Plaque Index
- PRISMA
Preferred Reporting Items for Systematic Reviews and Meta-Analyses
- RA
Rheumatoid Arthritis
- RCT
Randomized Controlled Trial
- RoB
Risk of Bias
- SMD
Standardized Mean Difference
- SRP
Scaling and Root Planing
- T2DM
Type 2 Diabetes Mellitus
- TNF-α
Tumor necrosis factor-alpha
Authors’ contributions
SW (Shuoyan Wu): Conceived and designed the study, conducted literature screening and data extraction, performed statistical analysis, and drafted the initial manuscript.YX (Yan Xuan): Assisted with data extraction and verification, created all figures and tables, and revised the manuscript for important intellectual content.XL (Xin Luo): Corresponding author, supervised the entire study design and implementation, revised the manuscript critically for all content, and approved the final version for publication. All authors read and approved the final manuscript.
Funding
This research received no external funding.
Data availability
The datasets used and/or analyzed during the current study are derived from the published randomized controlled trials included in this systematic review and meta-analysis. The detailed characteristics of the included studies are presented in the supplementary materials of this article, and the original data extraction table can be obtained from the corresponding author upon reasonable request. The search strategies for all the databases have been archived in searchRxiv and are available for public access.
Declarations
Ethics approval and consent to participate
Human Ethics and Consent to Participate declarations: not applicable. This systematic review and meta-analysis synthesized data from published randomized controlled trials and did not involve primary human or animal experiments, so ethical approval and informed consent were not required.
Consent for publication
Not applicable. This manuscript does not contain any individual person’s data, images, videos or case report details, thus no consent for publication is needed.
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
The datasets used and/or analyzed during the current study are derived from the published randomized controlled trials included in this systematic review and meta-analysis. The detailed characteristics of the included studies are presented in the supplementary materials of this article, and the original data extraction table can be obtained from the corresponding author upon reasonable request. The search strategies for all the databases have been archived in searchRxiv and are available for public access.