ABSTRACT
Background and Aim
Effective oral hygiene using different mechanical means is mainly dependent on the patient. Mouthwashes containing antimicrobial agents have been developed to be used as an adjunct to mechanical supragingival plaque control. The aim of this umbrella review is to evaluate and compare the long‐term efficacy of commonly used, commercially available daily mouthwashes in plaque control and gingival inflammation.
Methods
The current umbrella review was conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions using the PICOS format. The search was conducted in four databases: PubMed, Scopus, Cochrane and Web of Science. Nine systematic reviews/meta‐analyses (SRs/MAs) on the long‐term efficacy of commercially available mouthwashes (low‐concentration chlorhexidine [CHX], cetylpyridinium chloride [CPC], mouthwashes with essential oils [EOs], fluoride and oxygen‐releasing mouthwashes) were included.
Results
The results revealed that in all SRs/MAs, the prolonged daily use of mouthwashes helped in reducing plaque and gingival inflammation indices but not always with statistical significance.
Conclusions
Results of the present study indicate that the long‐term use of mouthwashes containing EOs seems to give the best results in both reducing plaque levels and improving gingivitis indices among all tested formulations.
Trial Registration: PROSPERO Registration Number CRD 42024618552
Keywords: daily use, gingival index, mouthwash, plaque index, umbrella review
1. Introduction
Oral hygiene using a combination of mechanical means is considered sufficient to remove the microbial dental biofilm and preserve gingival health (Sanz et al. 2020). The effectiveness of these aids depends upon the patient's dexterity, commitment and motivation, and therefore daily homecare in plaque control is often inadequate (Barouch et al. 2019). To overcome such limitations, mouthwashes containing antimicrobial agents have been developed. They are used only as a supplement to mechanical supragingival plaque control because, even though they are easy to use and effective at reducing the numbers of bacteria in their planktonic state, the characteristics of the bacterial biofilm limit their effectiveness as a monotherapy (Masadeh et al. 2013).
The active agents of mouthwashes are either chemical products such as chlorhexidine (CHX), cetylpyridinium chloride (CPC), hydrogen peroxide, hexetidine and others (James et al. 2017; Oo et al. 2023; Hossainian et al. 2011; Afennich et al. 2011; Hassandarvish et al. 2020), or herbal extract derivatives. Eucalyptol, menthol, peppermint, methyl salicylate, clove oil and thymol are some of the essential oils (EOs) associated with well‐known over‐the‐counter mouthwashes (Charugundla et al. 2015). In addition, natural products with antiseptic properties (tea tree oil, aloe vera) are useful as mouthwashes (Zhang et al. 2024; Al‐Maweri et al. 2020). Finally, extracts from curcumin, Salvadora persica, mastic, and so on, also constitute agents of mouthwashes, but are consumed mainly by the local communities where they are produced (Arunachalam et al. 2017; Jassoma et al. 2019; Tsironi et al. 2023).
Mouthwashes are used either during active periodontal therapy (PT) or as part of daily homecare. The use of CHX has been suggested (S3 guidelines) as an adjunct in the treatment of periodontitis stages I–III (Sanz et al. 2020). At high concentrations (≥ 0.12%), its long‐term use (most studies reporting up to 3 weeks since there is no evidence‐based literature on CHX use duration) results in, among others, tooth staining and irritation of the oral mucosa. Therefore, these products are not approved for prolonged use. However, lower CHX concentrations (0.05%/0.06%) along with other antibacterial agents can be used safely daily (James et al. 2017).
Several studies have evaluated the efficacy of these products in reducing plaque levels and in enhancing gingival health with encouraging results. Several systematic reviews (SRs) have been published on the subject, but in many original studies the effects of daily‐use mouthwashes are compared with those of CHX (≥ 0.12%) (Windhorst et al. 2025; James et al. 2017). However, high‐concentration CHX mouthwashes are not recommended for long‐term use, and therefore these comparisons cannot accurately disclose the actual benefit of daily mouthwashes.
An increasing tendency for mouthwash use by the general population for the prevention or treatment of gingivitis and periodontal disease (PD) has been observed. Taking into consideration that in the latest EFP guidelines it is unclear whether everyday use of commercially available mouthwashes can benefit patients with no PD or patients during supportive PT (the role of antiseptics in active PT or in supportive PT was not directly addressed in the SR of the European Workshop that led to the guidelines, while it is stated that adjunctive antiseptics, specifically CHX mouthwashes, may be considered for a limited period), a critical appraisal of the available data was deemed necessary.
Therefore, the aim of this umbrella review was to evaluate and compare the long‐term efficacy of commonly used and commercially available daily mouthwashes in plaque control and gingival inflammation when used as an adjunct to mechanical plaque removal.
2. Methods
2.1. Review Registration (Prospero) Design
The current umbrella review was conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions (Cumpston et al. 2019) and registered with an international prospective register of SRs and meta‐analyses (MAs) (PROSPERO) (Registration Number CRD 42024618552 14 December 2024).
2.2. PICOS
The review refers to adult individuals not currently under PT (Population), who are using commercially, and as widely available, over‐the‐counter daily homecare mouthwash (Intervention), compared to a placebo mouthwash and not a positive control such as CHX 0.12% (Comparative). Plaque index (PI) and gingival index (GI) or bleeding index (BI, modified BI) were assessed (Outcome). Only SRs/MAs including randomised controlled clinical trials (RCTs) were evaluated (Table 1).
TABLE 1.
PICO of included studies.
| Study no. | Studies | Participants | Intervention | Comparison | Outcome |
|---|---|---|---|---|---|
| 21 | Araujo et al. (2015) | Generally healthy men and women, 18 years or older, with mild to moderate levels of gingival inflammation and dental plaque but without signs of clinical periodontitis | EO‐containing mouthrinse | Daily mechanical plaque control (homecare) | MGI, PI |
| 2 | Figuero et al. (2019) | Systemically healthy patients with some degree of gingivitis at baseline | Anti‐plaque products, used adjunctively to mechanical oral hygiene measures with or without previous professional prophylaxis | Positive or negative control adjunctive to mechanical oral hygiene measures | Changes in plaque, gingival or bleeding indices |
| 3 | Gunsolley (2006) | Adults 18 years and older (presumed with gingivitis) | Antiplaque and/or anti‐gingivitis agents | Placebo or vehicle control | Anti‐plaque and anti‐gingivitis efficacy |
| 4 | Haas et al. (2016) | Systematically healthy participants with gingivitis | EO‐containing mouthrinse as adjuvant to mechanical oral hygiene | Comparison group always comprised a placebo solution, flossing, or CPC as adjuncts to mechanical plaque control | At least one measure of plaque and/or gingivitis |
| 5 | Haps et al. (2008) | Adults in good general health (periodontal status not determined) | CPC‐containing mouth rinses as adjuncts to toothbrushing | Toothbrushing only or toothbrushing plus placebo rinse | PI, GI, BI |
| 6 | Langa et al. (2021) | Adult individuals (periodontal status not determined) | CPC with manual toothbrushing | Placebo solution with toothbrushing or only toothbrushing | Interproximal plaque or gingivitis indices reductions |
| 7 | Van Leeuwen et al. (2014) | Adults with good general health (periodontal status not determined but selected studies included only participants with gingivitis) | EO‐based mouthrinse as an adjunct to self‐performed daily mechanical oral hygiene | Water‐based control or vehicle solution from a fixed formula of EO containing between 21.6% and 26.9% hydro‐alcohol |
Primary outcomes: plaque and gingivitis scores Secondary outcome: extrinsic tooth staining |
Abbreviations: BI, bleeding index; CHX, chlorhexidine; CPC, cetylpyridinium chloride; EO, essential oil; GI, gingival index; MGI, modified bleeding index; PI, plaque index.
2.3. Search Strategy—Inclusion and Exclusion Criteria
The search (Appendix A) was conducted in four databases: PubMed, Scopus, Cochrane CENTRAL and Web of Science. The literature search yielded a total of 3303 articles. After duplicate removal (1174), 2129 records were screened by title and/or abstract by two examiners (Y.A.B., P.A.K.). Of these, 112 articles were considered eligible for full text evaluation with a working team of six experts (W.P., P.A.K., Y.A.B., D.A.A., P.K., C.G.). Any disagreement was discussed within the team. Studies that did not fulfil the inclusion criteria were omitted (Appendix A). Finally, seven studies were included in the umbrella review (Figure 1).
FIGURE 1.

Preferred reporting items for systematic reviews and meta‐analyses (PRISMA) diagram for study selection.
The SRs/MAs had to meet the following inclusion criteria:
Include only RCTs.
Include only adults.
Include individuals with any periodontal diagnosis (gingivitis or periodontitis).
Include any commercially available, over‐the‐counter daily mouthwash as comprising the test group.
Include only placebo or mechanical oral hygiene as the control group.
Include any PI and/or GI as outcome measure.
Do not consider any time limit regarding the use of the daily mouthwash.
Consider only manuscripts in English language.
SRs and MAs were excluded if the included RCTs:
Assessed individuals under non‐surgical or surgical PT.
Assessed orthodontic patients or other special populations.
Reported any antimicrobial interventions other than adjunctive use of mouthwashes, such as use of dentifrices, gels, sprays, oil pulling, and so on.
Reported on non‐commercially available mouthwashes.
Used a positive control such as CHX (≥ 0.12%).
Assessed peri‐implantitis.
3. Results
The effect of various mouthwashes on plaque control and/or gingival inflammation was evaluated based on seven SRs/MAs. The demographic characteristics of the test subjects are summarised in Table 2. Studies were published between 2006 and 2021 with a follow‐up period of 6 months. Search timeline was from 1980 (Araujo et al. 2015) to 2020 (Langa et al. 2021). One study (Gunsolley 2006) did not report the search duration. Two studies (Araujo et al. 2015; Haas et al. 2016) included data from diverse populations (China, Africa, Tibet, Mongolia, Japan, India, Korea, Iran, Myanmar, USA, Canada, Switzerland), while five did not report on the population studied (Figuero et al. 2019; Gunsolley 2006; Haps et al. 2008; Langa et al. 2021; Van Leeuwen et al. 2014). The sample size varied from 720 participants (Langa et al. 2021) to 5775 (Figuero et al. 2019), with two studies (Gunsolley 2006; Van Leeuwen et al. 2014) not reporting on the population size. All studies included systemically healthy individuals with gingivitis except three (Haps et al. 2008; Langa et al. 2021; Van Leeuwen et al. 2014), which did not report the periodontal status. Intervention and comparator details are given in Table 1. PI and modified BI, mGI were assessed in all studies, while GI was assessed in eight (16, 17, 19–24) and BI in seven studies (16, 19–24).
TABLE 2.
Demographic characteristics of the included studies.
| Authors | No. of included RCTs | Total sample size | Country | Sources of search | Duration of search | Follow‐up period |
|---|---|---|---|---|---|---|
| Araujo et al. (2015) | 29 | 5106 | USA, Canada | Studies sponsored by Johnson & Johnson Consumer Companies and its predecessors | From 1980 to 2012 | 6 months or longer |
| Figuero et al. (2019) | 53 (21 for mouth rinses) | 8457 (5775 for mouth rinses) | N/R | PubMed CENTRAL | Up to 14 January 2019 | 6 months or longer |
| Gunsolley (2006) | 50 (at least 25 for mouth rinses) | N/R | N/R | Medline | N/R | 6 months or longer |
| Haas et al. (2016) | 14 | 2597 | USA, Canada, Switzerland, Brazil | MEDLINE‐Pubmed, EMBASE, Lilacs, and Scopus | Up to 1 April 2016 | 6 months or longer |
| Haps et al. (2008) | 8 | 867 | N/R | MEDLINE–PubMed and Cochrane Central Register of Controlled Trials. | Up to and including January 2008 | 6 weeks to 6 months |
| Langa et al. (2021) | 9 | 720 | N/R | SCOPUS and EMBASE | Up to 26 February 2020 | 6 weeks to 6 months |
| Van Leeuwen et al. (2014) | 5 | N/R | N/R | PubMed‐MEDLINE, Cochrane Central Register of Controlled Trials, and EMBASE | Up to and including September 2013 | 3 weeks to 6 months |
The seven included SRs/MAs assessed data from 62 primary RCTs, which appeared 110 times in the SRs/MAs. The overlap calculated by the ‘corrected covered area’ (CCA) was 12.9%, which is considered high (Pieper et al. 2014).
Of the included studies, one evaluated the effect of low‐concentration CHX (Figuero et al. 2019), four of CPC (Figuero et al. 2019; Gunsolley 2006; Haps et al. 2008; Langa et al. 2021), five of herbal mouthwashes with EOs (Araujo et al. 2015; Figuero et al. 2019; Gunsolley 2006; Haas et al. 2016; Van Leeuwen et al. 2014) and one each of fluoride (Figuero et al. 2019) and oxygen‐releasing mouthwashes (Figuero et al. 2019).
3.1. Quality Assessment (PRISMA, AMSTAR 2 GRADE)
The qualitative and quantitative characteristics of included studies are summarised in Tables 3 and 4, respectively.
TABLE 3.
Qualitative synthesis of the included studies.
| Study no. | Study | Methodology for quality assessment | Quality appraisal | Heterogeneity | Findings |
|---|---|---|---|---|---|
| 1 | Araujo et al. (2015) |
N/R Risk of bias was evaluated following the Cochrane handbook for systematic reviews of interventions |
There was a low risk of performance and detection bias in all 29 studies b/c the study personnel were masked to treatment assignment across all studies This analysis is not subject to publication bias, b/c publication was not considered in the inclusion of studies |
Significant heterogeneity among studies (study characteristics examined were supervision, baseline dental prophylaxis, flossing, study period, location). Other sources of heterogeneity: (a) gingival inflammation was assessed in some studies with MGI in others with GI and (b) the number of surfaces evaluated for PI was different among included studies | Clinically significant site‐specific benefit of adjunctive EO treatment in people within a 6‐month period |
| 2 | Figuero et al. (2019) | Cochrane Reviewers' Handbook (Higgins and Green 2011) | The evaluation of the risk of bias in individual studies, was made according to the Cochrane list and to the independency of the study. Publication bias was assessed using the Egger test, based on evidence of small‐study effects on p ≤ 0.1 | All PMA performed with two or more studies showed high heterogeneity, with I 2 values ranging from 74.6% to 96%. |
Mouth rinses containing EEOO_noAlc showed the greatest effect on GI scores, as assessed by NMA |
| 3 | Gunsolley (2006) | The inclusion criteria were clearly stated and divided into 7 domains | N/R | Antiplaque effect: the test for heterogeneity was statistically significant for CPC and EOs Anti‐gingivitis effect: significant heterogeneity was present for 0.12% CHX (p = 0.013), EOs (p < 0.001) and CPC (p = 0.004) | The studies in the SR provide strong evidence of the antiplaque, anti‐gingivitis effects of multiple agents and support the use of these agents as part of a typical oral hygiene regimen |
| 4 | Haas et al. (2016) | Cochrane Collaboration's tool | Overall analysis of risk of bias suggests that the quality of the studies included in this systematic review ranged from moderate to low. No publication bias was observed | High heterogeneity (I 2 = 97.8%, p < 0.001) was found | EO seems to be superior to placebo + MPC and CPC + MPC for reduction of plaque and gingival inflammation in patients with gingivitis |
| 5 | Haps et al. (2008) | Quality was based on following:
|
N/R | Considerable heterogeneity was observed in the interventions, regimens, concentrations of CPC, bio‐availability, outcome, the number, gender and age of participants | CPC containing mouth rinses, when used as adjuncts to either supervised or unsupervised oral hygiene, provide a small but significant additional benefit in reducing plaque accumulation and gingival inflammation |
| 6 | Langa et al. (2021) | RoB2 tool by Cochrane |
|
High heterogeneity was observed in both analyses for QHPI and GI (I 2 = 89% and I 2 = 98%, respectively) | CPC is efficacious both in plaque and gingival inflammatory parameters, demonstrating the potential to compensate for the limitations of interproximal plaque control |
| 7 | Van Leeuwen et al. (2014) | Van der Weijden's checklist | Quality assessment parameters, were based on evaluation of external, internal and statistical validity. Based on these criteria, the estimated risk of bias was low. Publication bias could not be used b/c fewer than 10 studies were included in MA | The majority of MA showed non‐important heterogeneity (I 2 value: 0%–9%) | EOMW appears to provide a significant oral health benefit during the 6 months of use and have an effect on plaque and gingivitis parameters that extends beyond the V‐Sol. Furthermore, the V‐Sol proved to be no different from WC |
Abbreviations: CHX, chlorhexidine; CPC, cetylpyridinium chloride; EO, essential oil; GI, gingival index; MA, meta‐analysis; MGI, modified gingival index; N/R, not reported; NaOCl‐MW, sodium hypochlorite mouthwash; NMA, network meta‐analysis; PI, plaque index; PMA, pairwise meta‐analysis; SR, systematic review; V‐Sol, alcohol vehicle solution; WC, water‐based control.
TABLE 4.
Quantitative synthesis of the included studies.
| Study no. | Authors | Meta‐analysis | Statistical analysis | Subgroup analysis | Sensitivity analysis | Significance/Direction |
|---|---|---|---|---|---|---|
| 1 | Araujo et al. (2015) | Yes | Treatment effect and SE estimates were obtained using a generalised linear model approach for the analysis of healthy sites and plaque free sites. This model was used to estimate the OR and associated SE within each study. The DerSimonian and Laird method was used to generate a pooled overall estimate of OR based on the random effects assumption. | Yes | NA | This meta‐analysis showed that addition of daily rinsing with an EO mouthrinse to mechanical oral hygiene provided statistically significantly greater odds of a cleaner and healthier mouth, 5.0 (95% confidence interval [CI], 3.3–7.5) and 7.8 (95% CI, 5.4–11.2) respectively. The percentage reductions in gingivitis and plaque at 6 months were 6.0 (95% CI: 11.3–20.7) and 27.7 (95% CI: 22.4–32.9), respectively |
| 2 | Figuero et al. (2019) | Yes | Results were combined using SMDs along with 95% CI. PMAs using a random‐effects model were performed. NMA was conducted to simultaneously compare the different active ingredients and placebo control for each delivery format. The NMA was performed using multivariate random‐effects meta‐analysis. The design‐by‐treatment interaction model was used to evaluate the assumption of consistency in the entire network. The surface under the cumulative ranking curve (SUCRA) was used to potentially rank the treatments | No | Yes. A sensitivity analysis resulted in a significant in‐consistency | The ranking of treatments according to SUCRA results from NMA was the following: EEOO_noAlc, EEOO, (tric_cop), CHX_H, CPC_H, CHX_L, AmF_SnF, CPC_L, alexidine, delmopinol and placebo. Results from NMA were similar to those obtained from PMA in terms of SMD, with all active agents showing greater reductions in GI than placebo control, although in the NMA comparisons, higher SMDs were found for CHX_H and CPC_H compared to PMA results. Statistically significant differences were found between CHX_H, EEOO, EEOO_noAlc and tric_cop versus placebo both in the PMA and in the NMA |
| 3 | Gunsolley (2006) | Yes | Standard difference in means and 95% CI were calculated at baseline and at 6 months. A random‐effects model was used to evaluate the overall efficacy of the data, when heterogeneity was present | Yes. Separate analysis of efficacy for each of the active agent was conducted. | N/R |
Anti‐plaque effect EOs: All but one study (total of 20 with 25 arms) showed statistical significance. Although the test for heterogeneity was positive, the study results clearly support the anti‐plaque efficacy of the essential oils (Std. Diff. = 0.852, p < 0.0001) CPC: great deal of heterogeneity in both the CPC agents evaluated and the results obtained, with some of the agents exhibiting antiplaque effects and some not exhibiting these effects Anti‐gingivitis effect EOs: The results of one‐ half of the studies were statistically significant for each agent, but all of the studies demonstrated anti‐gingivitis effects. CPC: difficult to reach conclusion due to heterogeneity. Use of MGI will improve researchers' ability to show differences between active and placebo agents |
| 4 | Haas et al. (2016) | Yes | Means and SDs at 6mo of each trial group (with and without EO) were used to estimate the WMD and its 95% CI. RETD was estimated for comparisons between EO + MPC and placebo + MPC regarding the QHI and the MGI, and a WMD was estimated and reported. Linear meta‐ analysis was applied. Heterogeneity was assessed by the Q test and quantified with the I 2 statistic. Random effects models were applied using the DerSimonian and Laird method because of high heterogeneity across studies. Pooled WMD were investigated using linear meta‐regression when the number of included studies was more than 10 and heterogeneity was higher than 40%. | Yes | NA |
Mouthwashes containing EOs should be considered the first choice for daily use as adjuvants to self‐performed MPC MAs comparing EO and placebo solution: All studies demonstrated statistically significant differences in favour of EO for Q‐H, but with high heterogeneity (I 2 = 97.8%, p < 0.001) and for all gingivitis indices. MA comparing EO and CPC: Statistically lower levels of plaque and gingivitis. The respective WMD values for Q‐H and MGI were −0.75 and −0.52. MA comparing EO, placebo and flossing in the proximal area: EO had a significantly higher decrease in the Q‐H index (WMD = −0.95, 95% CI –1.26 to −0.63; I 2 = 96.0% p < 0.001) and in MGI (WMD = −0.34, 95% CI –0.53 to −0.15; I 2 = 98.9% p = 0.001) compared to placebo in the proximal area. When EO was compared to brushing and flossing regarding levels of plaque in the interproximal area, there was significantly lower levels in favour of EO but there was no significant difference regarding gingivitis. Meta‐regression: High heterogeneity (I 2 > 95%) was found and explained (MGI—R 2 = 63.6%; QHI—R 2 = 80.1%) by differences between studies in the percentage of males, supervision of the mouthwashes and provision of oral hygiene |
| 5 | Haps et al. (2008) | Yes | Mean values and standard deviations were obtained by data extraction | Yes | NA | In all cases, baseline scores were not statistically different. The end scores showed a significant effect for the QHPI in favour of the CPC group compared to those of toothbrushing only or toothbrushing followed by a placebo rinse (weighted mean difference [WMD]:0.50, p < 0.00001; test for heterogeneity p = 0.002, I 2 = 71.6%). The heterogeneity was greater for intermediate‐length studies (I 2 = 68.1%) than long‐term studies (I 2 = 58.8%). The end scores also displayed a significant effect for the GI in favour of the CPC group compared to toothbrushing only or toothbrushing followed by a control rinse group (WMD: 0.25, p < 0.00003; test for heterogeneity p = 0.0001, I 2 = 87.0%). |
| 6 | Langa et al. (2021) | Yes | Two meta‐analyses were performed for the Turesky modification of the QHPI and the Löe and Silness GI. For both analyses, the MD between baseline and 6 weeks were calculated using a random‐effect model | Yes. Subgroup analyses were created for both meta‐analyses because of different concentrations of CPC used and because of different follow‐up periods using the same indices | NA | The meta‐analysis demonstrated that groups that used CPC displayed a significantly greater reduction in the plaque index score (MD; 95% confidence interval [95% CI]: −0.70; −0.83 to –0.57) and in the gingival index (MD; 95% CI: −0.38; −0.47 to –0.28) when compared to placebo |
| 7 | Van Leeuwen et al. (2014) | Yes |
DIFFMs were calculated with Review Manager3 using a random‐effect model or a fixed‐effect model In case there are < 4 studies included Heterogeneity was tested by chi‐squared test and the I 2 statistic. A Chi‐squared test resulting in a p < 0.1 was considered an indication of significant statistical heterogeneity |
No. | No. Sensitivity analysis could not be conducted because of the limited number of included studies. |
The 6‐month brushing studies that evaluated QH modified by Turesky showed a significant effect in favour of the EOMW when compared to the V‐Sol, with a difference in means of 0.39 [95% CI = (0.30; 0.47), p < 0.00001]. A significant effect was also found in favour of the EOMW for GI with a DIFFM of 0.36 [95% CI = (0.26; 0.62), p = 0.0001], and MGI with a DIFFM of 0.17 [95% CI = (0.08; 0.25), p < 0.001]. When the V‐Sol was compared to WC, no significant difference was found for either the plaque scores or the gingivitis reduction, DIFFM = 0.04 [95% CI = (0.09; 0.18), p = 0.51] and DIFFM = 0.03 [95% CI = (0.06; 0.13), p = 0.51], respectively |
Abbreviations: alexi, alexidine; AmF_SnF, amine and stannous fluoride; BI, bleeding index; CI, confidence interval; CPC, cetylpyridinium; delmo, delmopinol; DIFFMs, differences of means; EEOO, essential oils; H, high concentration; L, low concentration; MGI, modified gingival index; MPC, mechanical plaque control; NA, not applicable; NMA, network meta‐analysis; QHPI, Quigley‐Hein Plaque Index; RETD, relative end‐of‐trial difference; SMD, standardized mean difference; tric_cop, triclosan copolymer; WMD, weighted mean difference.
Three studies (Araujo et al. 2015; Langa et al. 2021, Van Leeuwen et al. 2014) reported a low risk of bias (RoB) and one (Haas et al. 2016) moderate to low, while two (Gunsolley 2006; Haps et al. 2008) did not report the RoB. Regarding heterogeneity, all studies (Araujo et al. 2015; Figuero et al. 2019; Gunsolley 2006; Haas et al. 2016; Haps et al. 2008; Langa et al. 2021) reported significant or high heterogeneity (I 2 value ranging from 74.6% to 98% depending on the study) except one (Van Leeuwen et al. 2014) which found non‐important heterogeneity (I 2 value: 0%–9%).
MA was performed on all selected studies. Regarding statistical analyses, six studies (Araujo et al. 2015; Figuero et al. 2019; Gunsolley 2006; Haas et al. 2016; Langa et al. 2021; Van Leeuwen et al. 2014) applied a random‐effects model; one (Araujo et al. 2015) used the generalised linear model approach to determine the odds ratio (OR); and one (Haps et al. 2008) reported outcomes as mean values with standard deviations (SDs).
Regarding quality appraisal of the selected studies, the AMSTAR 2 tool was used (Shea et al. 2017). All seven SRs/MAs had a defined PICO and included RCTs only. No SR/MA was registered apart from Araujo et al. All SRs/MAs, except for Gunsolley, used a comprehensive literature search and performed both study selection and data extraction in duplicate. Only Figuero et al. provided a full list, whereas Araujo et al. gave a partial list of the excluded studies with justification for the exclusions. All seven SRs/MAs described the included studies in detail. RoB was assessed fully in all SRs/MAs but only partially in Gunsolley. Except Araujo et al., no other SR/MA reported on the sources of funding of the included studies. All authors used appropriate methods for statistical combination of results. Except for Gunsolley's study, which did not assess but only partially accounted for RoB of the selected studies, all other SRs/MAs partially did so and assessed the RoB in the interpretation of results. All SRs/MAs provided an explanation for the heterogeneity observed in the studies. Apart from Gunsolley et al. and Haps et al., all other SRs/MAs reported on publication bias. Finally, all SRs/MAs reported on conflicts of interest. Taking into consideration the above, which are the answers to the 16 questions of the AMSTAR 2 instrument (Shea et al. 2017), Araujo et al. had a ‘high’ confidence rating, Figuero et al. ‘moderate to high’, Haas et al., Langa et al. and Van Leeuwen et al. ‘moderate’, Haps et al. ‘low to moderate’ and Gunsolley ‘low’ (Figure 2).
FIGURE 2.

AMSTAR 2 (a measurement tool to assess systematic reviews) tool of the included studies. NA, not applicable; YES: YES; NO: NO; PAR: PARTIAL YES. AMSTAR 2 items (Shea et al. 2017).
The certainty of evidence was assessed by the GRADE system. Under GRADE, all RCTs start as ‘high’ quality of evidence, and can be downgraded considering factors such as study design, RoB, inconsistency, indirectness, imprecision and publication bias. This systematic approach ensures a comprehensive evaluation of the evidence base (Guyatt et al. 2011). Regarding the RoB for the selected studies, those by Araujo et al., Figuero et al. and Van Leeuwen et al. have been assessed as having a low RoB since they only included RCTs that provided information on allocation concealment, blinding and completeness of outcome data, and they were not downgraded in the GRADE system. The remaining four studies were downgraded. The study by Langa et al. included RCTs that did not report properly on their randomisation sequence both for plaque and bleeding indices. Haas et al. had all RCTs but they were funded by the industry and most of them provided unclear information for random sequence generation while only four provided clear information regarding allocation. Overall, the quality of the studies included in this SR ranged from moderate to low. In Haps et al., all studies but one were RCTs. Allocation concealment reporting is absent or unclear in all the studies but two. Finally, Gunsolley's is an older study with poor reporting for both randomisation and allocation concealment, while many of the included studies are industry sponsored. With all the above GRADE (Guyatt et al. 2011) factors considered, Araujo et al., Figuero et al. and Van Leeuwen et al. were categorised as ‘high’, Gunsolley as ‘moderate’ and Haas et al., Haps et al. and Langa et al. as ‘low’ in the assessment (Figure 3).
FIGURE 3.

GRADE (grading of recommendations assessment, development, and evaluation) tool of the included studies.
3.2. Effect of Mouthwashes Containing Low‐Concentration CHX (< 0.10%)
The efficacy of the daily use of low‐concentration CHX (< 0.10%) on gingival health was assessed only in one SR/MA (Figuero et al. 2019). A reduction, although not statistically significant, in GI was reported; however, the data were derived only from a single RCT including 33 participants.
3.3. Effect of Mouthwashes Containing CPC
Four SRs/MAs (Figuero et al. 2019; Gunsolley 2006; Haps et al. 2008; Langa et al. 2021) evaluated the effect of CPC‐containing mouthwashes on gingival health. Figuero et al. analysed the effect of CPC based on its concentration. In four RCTs (429 participants), CPC concentration was ≤ 0.05% (CPC_L), while in three RCTs (292 participants) the concentration was > 0.05% (CPC_H). In all RCTs, CPC reduced the GI but failed to reach statistical significance.
The effect of CPC was also assessed by Haps et al. (six RCTs). The end scores of the MA showed a significant effect on the Quigley and Hein PI (QH‐PI) in favour of the CPC group compared to toothbrushing alone or toothbrushing followed by a placebo rinse (weighted mean difference [WMD] 0.50, p < 0.00001). However, high heterogeneity was observed among the RCTs (I 2 = 71.6%, p = 0.002). Likewise, the end scores also showed a significant effect on the GI in favour of the CPC group (WMD 0.25, p < 0.00003), although, again, the heterogeneity among the RCTs was high (I 2 = 87.0%, p = 0.0001).
Similarly, the MA by Langa et al. (nine RCTs) showed that, compared to placebo, CPC displayed a significantly greater reduction both in PI (mean difference [MD] −0.70; 95% CI [−0.83 to −0.57]) and GI (MD −0.38; 95% CI [−0.47 to −0.28]). However, high heterogeneity was observed in both analyses (I 2 = 89% and 98%, respectively). The indices used were the Turesky modification of QH‐PI and Löe and Silness GI.
Finally, in the efficacy analysis performed by Gunsolley, four out of seven RCTs showed a statistically significant improvement in GI for the CPC group. According to the author, it was difficult to reach a solid conclusion regarding CPC efficacy due to the heterogeneity among the RCTs, with some agents exhibiting anti‐plaque effects while others did not. Specifically, the mouthwashes evaluated were not comparable because the concentration of CPC used varied significantly (0.045%–0.07%), and some mouthwashes had an alcohol vehicle while others did not.
3.4. Effect of Mouthwashes Containing EOs
Herbal mouthwashes containing EOs are the most studied commercially available mouthrinses for daily use. Haas et al. performed a MA and meta‐regression of 14 and 11 RCTs to evaluate changes in QH‐PI and MGI, respectively. The reductions in plaque and gingival inflammation were 32% and 24% higher in the EO groups compared to placebo. Among the two groups, WMD for the QH‐PI was 0.95 (95% CI: 1.26–0.63, p < 0.001) and for MGI 0.3495 (95% CI: 0.53–0.15, p = 0.001). However, the authors reported high heterogeneity (I 2 > 95%) among the included RCTs, possibly due to differences in the percentage of males, supervision in the use of the mouthwashes and provision of oral hygiene. Nevertheless, the RoB of the selected studies ranged from moderate to low. These results are in accordance with those by Van Leeuwen et al. Their MA of four RCTs showed that mouthwashes containing EO provided significantly better plaque control and reduction of gingival inflammation compared to an alcohol‐based solution V‐Sol. The difference of means in plaque scores was 0.39 (p < 0.00001), while in gingival inflammation it was 0.36 (p = 0.00001) (Löe and Silness Index). The reported RoB was considered low.
The study by Araujo et al. (32 RCTs, 5106 participants) compared the effect of EO‐containing mouthwashes versus mechanical plaque control. A statistically significant reduction in PI and gingivitis was found at 6 months in favour of the EO group. Responder analyses using aggregate individual‐level data showed that 36.9% and 44.8% of the participants using additionally an EO‐containing mouthwash achieved at least 50% plaque‐free and healthy sites, respectively. In subjects performing only mechanical plaque control, the percentage was 5.5% and 14.4%, respectively. RoB was assessed as low.
Gunsolley reported that in 20 RCTs that evaluated mouthwashes containing different EOs only, one failed to show a statistically significant difference in plaque control in favour of EO. Although the heterogeneity among the studies was high, the authors supported the anti‐plaque efficacy of EO‐based mouthwashes (SD 0.852, p < 0.0001). Regarding gingivitis, 13 of the 17 RCTs revealed statistically significant anti‐gingivitis properties of EOs compared to control agents. Again, although there was significant heterogeneity (p < 0.0001) among studies, all favoured the EO group over the control mouthwash group (Std. Diff. 0.762).
Finally, Figuero et al. (2019) stratified the RCTs evaluating the effect of EOs on gingival inflammation in two groups. The first group (11 RCTs, 1009 participants) had an alcoholic solution of EO and the second group (one RCT, 107 subjects) had a non‐alcoholic solution of EO. In both EO groups, GI improved, but not significantly.
3.5. Effect of Mouthwashes Containing Fluoride or H2O2
The effect of sodium fluoride (NaF) and thiocyanate/carbamide peroxide (SCN_H2O2) mouthwashes on gingival health was assessed in one SR and MA (Figuero et al. 2019). For both antimicrobial agents, there was only a non‐significant benefit in reducing the GI. These results were derived from three RCTs (732 participants) and one RCT (140 participants) for NaF and SCN_H2O2, respectively.
3.6. Comparison of the Effect of Different Mouthwashes on Gingival Health
Only the SR/MA by Figuero et al. tried to rank the different types of mouthwashes according to their efficacy in improving plaque control and/or gingival inflammation. In their network MA (NMA), the ranking of treatments according to SUCRA results from best to worst was as follows: EO in no‐alcohol solution, EO, high‐concentration CPC, low‐concentration CHX, AmF_SnF, low‐concentration CPC, alexidine, delmopinol and placebo. Results from NMA and MA were similar in terms of standardised mean differences (SMD), with all active agents showing greater reductions in GI than placebo control, although in the NMA comparisons, higher SMDs were found for high‐concentration CPC compared to MA results. Statistically significant differences were found between EO and EO in no‐alcohol solution versus placebo both in MA and NMA.
4. DISCUSION
The EFP in its recent clinical guidelines regarding the treatment of periodontitis stage I–III states that ‘the basis of the management of gingival inflammation is self‐performed mechanical removal of biofilm although, adjunctive measures, including antiseptic mouth rinses, may be considered in specific cases, as part of a personalized treatment approach’ (Sanz et al. 2020). Mouthwashes containing CHX 0.12% and 0.20% are considered the gold standard in enhancing gingival health (James et al. 2017). However, the use of these products for a prolonged period is not recommended because of their side effects (James et al. 2017).
Another point of concern about mouthwashes is the emerging evidence regarding their potential effect on blood pressure (BP) regulation. Mouthwashes, through their antimicrobial action, alter the oral cavity's microbial composition, and this affects the nitrate–nitrite–nitric oxide pathway (enterosalivary pathway) which is vital to BP regulation (Duncan et al. 1995; Senkus and Crowe‐White 2020). Related human studies are scarce, and even though they demonstrate a negative effect of mouthwash use (Bondonno et al. 2015; Kapil et al. 2013), the product used in most of the studies is CHX ≥ 0.12%, which is not a mouthwash for everyday use. When various types and strengths of commercially available mouthwashes (including everyday‐use products) were evaluated, results suggested that the stronger mouthwashes (CHX ≥ 0.12%) led to elevated systolic BP after 3–7 days, while mouthwashes containing EO or CPC did not negatively affect any outcome (Woessner et al. 2016).
Therefore, several other mouthwashes that are commercially available have been designed for daily homecare. These products mainly contain chemical antibacterial agents such as CPC or low‐concentration CHX, or are derived from herbal extracts. Although a large body of evidence supports their long‐term use, many studies have compared their efficacy to that of the short‐term‐use gold standard. This may not accurately reflect their contribution to controlling gingival inflammation and thus may underestimate their importance in daily use. Therefore, the purpose of this study was to assess and compare the efficacy of these long‐term‐use daily mouth rinses by evaluating SRs/MAs that examined RCTs where the control group was a placebo mouth rinse.
The present results showed that in all SRs/MAs, prolonged daily use of mouthwashes had a positive effect on plaque control and gingival inflammation. However, this did not reach statistical significance in several studies. The findings indicate that mouthwashes containing EOs gave the best results both in reducing plaque levels and in improving gingivitis indices among the tested formulations. EO‐based mouthwashes were the most studied and exhibited improvement in PI and GI in three studies with statistical significance in both indices and in two with no statistical improvement in GI. Next in efficacy was CPC, which demonstrated an improvement in PI and GI in all four SRs/MAs, which showed statistical significance for PI in all studies (Figuero et al.; Gunsolley; Haps et al.; Langa et al.) but failed to reach statistical significance for GI in two (Figuero et al.; Gunsolley).
Although umbrella reviews are considered to lead to conclusions, the results from the current study need to be interpreted with caution because of methodological inconsistencies among the RCTs in the SRs/MAs included. Specifically, the RCTs used many different indices for plaque control or gingival inflammation, which limits direct comparisons. Even in cases where these indices were similar as they derive from one another (i.e., Silness & Löe 1964 PI, and Simplified Silness & Löe, PI), data still required statistical manipulations/conversions to enter an MA. Indeed, a high inconsistency was observed in most MAs, which weakened the final conclusions of the individual SR. Another issue is that, although in total the included SRs examined the effect of a large number of different antimicrobial agents in mouthwashes, some of these products were severely under represented in the current analysis. Hence, from the nine SRs included, the majority evaluated mouthwashes containing EO or CPC (five and four studies, respectively), while low‐concentration CHX, fluoride and H2O2 were assessed only by one SR, which included a small number of RCTs. Therefore, the available body of evidence is not sufficient to accurately estimate the effect of all the mouthwashes studied and safely rank their efficacy. One should always bear in mind that mouthwashes may not be of much value in those subjects with periodontal health or low risk for caries. One should take into consideration the potential risks of allergic reactions, the dysbiosis of the oral microbiota, the emergence of antimicrobial resistance, deleterious effects on the environment related to the wide use of mouthwashes (Brookes, McCullough, et al. 2023) and the possible negative effect on BP. Regarding dysbiosis and antimicrobial resistance, little is known about the effects of mouthwashes on fungi and viruses in the oral microbiome (virome) in vivo, despite the existing in vitro evidence that they ‘kill’ certain viral pathogens Furthermore, there is growing concern that the use of mouthwashes may lead to antimicrobial resistance, and this should be further considered in the context of their widespread use by clinicians and patients (Brookes, Teoh, et al. 2023).
Another limitation of the present study is the use of studies only in English language. Finally, there was no uniformity in the RoB reported, although for most RCTs it was estimated to be moderate to low.
5. Conclusion
In conclusion, all SRs/MAs demonstrated that the additional use of mouthwashes to daily toothbrushing improved both plaque control and gingival inflammation to varying degrees. This may not have been statistically significant every time, but there still remains a positive effect for all formulations tested.
The data derived from this umbrella review demonstrate that the long‐term daily use (up to 6 months) of mouthwashes containing EOs or CPC may enhance gingival health when they are used as an adjunct to mechanical plaque control. However, one cannot ignore the presence of critical methodological limitations of the RCTs, which may question the strength of the available evidence. Therefore, studies with a sound methodology, low RoB and a larger population are needed in order to evaluate safely the additional benefit that these mouthrinses may bring in everyday oral care.
Acknowledgements
Findings of the present umbrella review are the result of the joint workshop of the Hellenic Society of Periodontology and Implant Dentistry and the Hellenic Society of Preventive Dentistry, which took place in Ioannina, Greece, from 8 to 10 November 2024. This study was supported by an educational grant from Johnson & Johnson Hellas. The publication of this article in OA mode was financially supported by HEAL‐Link.
Appendix A.
Search Strategy
| Database | Search strategy | Hits |
|---|---|---|
| PubMed | ((mouthwash) OR (“mouth wash”) OR (mouthrinse) OR (“mouth rinse”) OR (gargle) OR (collut*) OR (“mouth solution”) OR (“oral solution”) OR (“oral rinse”) OR (“oral antiseptic”)) AND (systematic OR meta‐analys* OR metanalys*) | 1622 |
| Cochrane Central Register of Controlled Trials | ((mouthwash) OR (“mouth wash”) OR (mouthrinse) OR (“mouth rinse”) OR (gargle) OR (collut*) OR (“mouth solution”) OR (“oral solution”) OR (“oral rinse”) OR (“oral antiseptic”)) AND (systematic OR meta‐analys* OR metanalys*) in Title Abstract Keyword | 100 |
| Cochrane Database of Systematic Reviews | ((mouthwash) OR (“mouth wash”) OR (mouthrinse) OR (“mouth rinse”) OR (gargle) OR (collut*) OR (“mouth solution”) OR (“oral solution”) OR (“oral rinse”) OR (“oral antiseptic”)) AND (systematic OR meta‐analys* OR metanalys*) in Title Abstract Keyword | 29 |
| Scopus | TITLE‐ABS‐KEY (((mouthwash) OR (“mouth wash”) OR (mouthrinse) OR (“mouth rinse”) OR (gargle) OR (collut*) OR (“mouth solution”) OR (“oral solution”) OR (“oral rinse”) OR (“oral antiseptic”)) AND (systematic OR meta‐analys* OR metanalys*)) | 827 |
| Web of Science | ((mouthwash) OR (“mouth wash”) OR (mouthrinse) OR (“mouth rinse”) OR (gargle) OR (collut*) OR (“mouth solution”) OR (“oral solution”) OR (“oral rinse”) OR (“oral antiseptic”)) AND (systematic OR meta‐analys* OR metanalys*) (Topic) and Preprint Citation Index (Exclude—Database) | 725 |
Excluded Studies and Reasons for Exclusion
| Study (main reason) | Reason for exclusion |
|---|---|
| 1. Yong Chen et al. 2013 | Non‐commercial formulations |
| 2. Hossainian et al. 2011 | Positive control CHX |
| 3. Swaaij et al. 2024 | Tests the vehicle for CHX |
| 4. Serrano et al. 2015 | Too many formulations |
| 5. Keremi et al. 2020 | Positive control |
| 6. Janakiram et al. 2020 | Positive control |
| 7. Kairey et al. 2023 | Herbal, positive control mixed compounds |
| 8. Amanpour et al. 2023 | Too many types of formulation |
| 9. Kumar 2023 | No mouthwash |
| 10. Chatzopoulos et al. 2022 | During treatment |
| 11. Janakiram et al. 2020 | Herbal, positive control, mixed compounds |
| 12. Mathur et al. 2018 | Methodological fault |
| 13. Mehta et al. 2018 | Toothpaste |
| 14. Dhingra & Vandana 2017 | Non‐commercially available positive control |
| 15. Sunayuana Manipal et al. 2016 | Short |
| 16. Monica Prasad et al. 2016 | Non‐commercially available positive control |
| 17. Tafazoli et al. 2020 | Methodological fault |
| 18. Alshehri et al. 2018 | Ortho patients |
| 19. Fakheran et al. 2019 | Treatment |
| 20. Ingle 2021 | Formulations in various forms |
| 21. AlJameel & Almalki 2020 | Positive control CHX |
| 22. Jassoma et al. 2019 | Positive control |
| 23. Merchant et al. 2022 | Active treatment, special population |
| 24. Furquim dos Santos Cardoso et al. 2021 | Methodological fault |
| 25. Javed et al. 2023 | Methodological fault mixed population |
| 26. Konopka et al. 2015 | Polish language |
| 27. Suresh et al. 2021 | Toothpaste |
| 28. Terby et al. 2021 | Treatment |
| 29. McGrath 2018 | Special population |
| 30. Affenich et al. 2010 | Not for everyday use Hexetidine |
| 31. Alroudhan et al. 2021 | Methodological fault |
| 32. Perez – Nikolas et al. 2023 | Out of scope |
| 33. Khijmatgar et al. 2021 | Oil pulling |
| 34. Angelilo et al. 2002 | Change in formulation (previously with Triclosan) |
| 35. Riley & Lamont 2013 | Toothpaste |
| 36. Santi et al. 2019 | Mixed comparators |
| 37. Supranoto et al. 2014 | Toothpaste gel |
| 38. Svellenti et al. 2024 | Perio treatment |
| 39. Tafazoli &Tafazoli 2020 | Duplicate |
| 40. James et al. 2017 | Low quality; no specific data; few studies; low CHX |
| 41. Matesanz – Perez 2013 | Professional appliance |
| 42. Vanstrydonk et al. 2012 | Positive control CHX |
| 43. Zaffar & Ullah 2021 | Microbiology |
| 44. Zhang et al. 2018a | Spray |
| 45. Zhang et al. 2023 | Active treatment |
| 46. Zhang et al. 2018b | Spray |
| 47. Zhou etal 2018 | Special population |
| 48. Barboza et al. 2023 | Oral Pathology |
| 49. Bunte et al. 2019 | No RCT |
| 50. Canullo et al. 2020 | Surgical |
| 51. Casarin et al. 2023 | Post surgical |
| 52. Cosyn et al. 2005 | Gel |
| 53. Grover et al. 2021 | No RCT |
| 54. Johannsen et al. 2019 | Dentifrice CHX |
| 55. Langa et al. 2022 | Not mouthwash |
| 56. Jong et al. 2023 | Oil pulling |
| 57. Da Costa 2017 | Mechanical therapy |
| 58. Boyle et al. 2014 | Faulty methodology |
| 59. Al Maweri et al. 2022 | CHX |
| 60. Elkerbout et al. 2019 | CHX |
| 61. Gunsolley 2010 | Report |
| 62. Housain et al. 2022 | Self preparatory |
| 63. Prasad et al. 2016 | Too Vague no focused question |
| 64. Halboob et al. 2020 | CHX |
| 65. Adam et al. 2023 | Herbal Salvadora Persica |
| 66. Paraskevas et al. 2006 | Dentifrice |
| 67. Inchingolo et al. 2024 | Faulty methodology |
| 68. Alsehri et al. 2018 | Ortho and oral pathology patients |
| 69. Shirban et al. 2021 | Faulty methodology |
| 70. Berchier et al. 2010 | CHX |
| 71. Minervini et al. 2024 | CHX |
| 72. Lopez et al. 2019 | Oral pathology |
| 73. Addy et al. 2007 | Not available |
| 74. Swaaij et al. 2020 | CHX |
| 75. Chye et al. 2019 | Surgical CHX |
| 76. De Asis et al. 2021 | No mouthwash not commercially available |
| 77. De Silva et al. 2016 | Out of scope |
| 78. Freires et al. 2012 | Treatment non commercially available |
| 79. Garcia et al. 2008 | CHX 0.12% |
| 80. Gartenmann et al. 2020 | Not commercially available |
| 81. Hendiani et al. 2022 | Not commercially available |
| 82. Slot et al. 2008 | Commentary |
| 83. Van Strydonck et al. 2012 | CHX 0.12% |
| 84. Hwu & Lin 2014 | Out of focus |
| 85. Jadhav et al. 2021 | Too many formulations, gel |
| 86. Kolahi 2006 | Out of focus |
| 87. Lopez Valverde et al. 2021 | Treatment |
| 88. Haas et al. 2017 | Summary |
| 89. Santi et al. 2019 | Not commercially available |
| 90. Solderer et al. 2018 | CHX after surgery |
| 91. Serano et al. 2015 | Commentary |
| 92. Xhang et al. 2021 | After non‐surgical treatment |
| 93. Santi et al. 2021 | Not commercially available |
| 94. Cosyn et al. 2005 | Gel |
| 95. Stoeken et al. 2007 | CHX |
| 96. Housain et al. 2022 | Self‐preparation |
| 97. Muniz et al. 2020 | Not commercially available |
| 98. Inchingolo et al. 2024 | Faulty methodology |
| 99. Berchier et al. 2010 | CHX |
| 100. Balouk et al. 2025 | Self‐preparatory |
| 101. Bunte et al. 2019 | No RCT |
| 102. Escribano et al. 2016 | Too many formulations, CHX |
| 103. Keremi et al. 2020 | Positive control |
Koromantzos, P. A. , Bobetsis Y. A., Giota C., et al. 2026. “Effect of Adjunctive Use of Commercial Daily Mouthwashes on Periodontal Health: An Umbrella Review.” Journal of Clinical Periodontology 53, no. 3: 407–423. 10.1111/jcpe.70061.
Funding: This study was supported by an educational grant from Johnson & Johnson Hellas.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
