Introduction

Periodontitis is a major public health problem and a significant burden to the healthcare economy.1 In total, 54 billion USD/year is the global cost of lost productivity due to severe periodontitis.2 It is characterised by inflammation of the supporting structures of the teeth with resulting bone and soft tissue loss and eventual tooth loss if left untreated.3 The prevalence of periodontal disease in India has been estimated to be in the range of 86.5-100%.4 Moreover, periodontal disease can impact systemic health through several direct and indirect pathways.5,6 Management of periodontal disease is thus a critical element for maintaining overall health and reducing the economic and disease burden worldwide. Bacterial colonisation forming a biofilm that adheres to tooth surfaces and gingiva is the main aetiology of periodontitis.7 Gram-negative anaerobic bacteria, such as Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Fusobacterium nucleatum and Treponema denticola are some of the pathogens present in the biofilm that are implicated in the aetiology of periodontal disease.8 Thus, periodontal therapy primarily involves the removal of the plaque microbiota and balances the inflammatory response in the periodontal tissues.9 Mechanical plaque control with or without adjunctive use of chemical plaque control agents constitutes one of the initial steps of the etiotropic phase of periodontal therapy.10

Several chemical plaque control agents have been in use and chlorhexidine (CHX), which is a broad spectrum antiseptic agent, is considered as a gold standard anti-plaque and anti-gingivitis agent. It acts as an antibacterial agent through disruption of the bacterial cell membrane, increasing the permeability of the cell membrane and resulting in cell lysis. It can be either bacteriostatic or bactericidal, depending on the dose. The side effects like permanent staining of teeth and dysgeusia have been noticed associated with CHX.11 Although non-staining CHX has been researched upon, diversification of research has delved into the use of alternate anti-plaque and anti-gingivitis agents and the search has extended into the field of herbal medicine also.

Studies have shown that traditional herbal medicines and fruits can be used in the prevention or treatment of oral disease due to their ability to inhibit the adhesion of pathogenic biofilms in the oral cavity.12 Extracts of acacia catechu, aloe vera, azadirachta indica, glycyrrhiza glabra, cinnamomum zeylanicum, allium sativum, propolis, mikania laevigata, mikania glomerate, drosera peltata, helichrysumitalicum, coptidis rhizoma, piper cubeba, azadirachta indica, syzygium aromaticum and tea tree oil (TTO) are some of the herbal medicines used in the treatment of periodontal therapy.13 TTO is an essential oil extracted from the leaves of Melaleuca alternifolia,which belongs to the family Myrtaceae. Many studies have reported that TTO exerts strong antibacterial, antifungal, antiviral and anti-inflammatory activities (Fig. 1). It contains α-terpineol and terpinen-4-ol, which have been shown to inhibit the growth of Staphylococcus aureus and Escherichia coli. Terpinen-4-ol and 1,8-cineol have also been shown to inhibit the adhesion of P. gingivalis and reduce inflammation in oral tissue. Thus, TTO has the potential to treat gingivitis.13 According to a study conducted by Abdul Gani Soulissa et al., the P. gingivalis and A. actinomycetemcomitans colony counts on enamel surfaces treated with all concentrations of TTO were lower than those in the negative control. These results indicated that TTO inhibited the adhesion of P. gingivalis and A. actinomycetemcomitans biofilms to enamel surfaces significantly.14 It has also been observed that the local delivery of TTO gel in case of chronic periodontitis may have some beneficial effects to augment the results of conventional periodontal therapy. It can result in enhanced clinical results without any systemic side effects and bacterial resistance.15

Fig. 1
figure 1

Mechanism of action of tea tree oil

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Although TTO is seen to be efficacious in controlling periodontal inflammation and plaque formation, there is still no evidence that confirms if it can be an alternative to CHX for the management of periodontal diseases. Therefore, the present review aims to systematically appraise whether TTO can be used as an alternative to CHX to effectively limit plaque accumulation and maintain periodontal health. This review consolidates the existing evidence to show if TTO can be a viable alternative for managing periodontal diseases.

Method

Protocol and registration

The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). This systematic review was registered with PROSPERO (#CRD42021241323).

Focus question

The review aims to answer the question of whether TTO (intervention) is a viable alternative to CHX (comparator) for the management of gingival and periodontal disease (outcomes) in adolescents and adults (population). The main objective of this review is to answer the following questions:

  • Can TTO be used as an alternative to CHX for controlling gingival inflammation?

  • Can TTO be used as an alternative to CHX for controlling biofilm formation?

Search strategy and keywords

The following keywords were used: patients with periodontal disease; OR periodontitis; OR gingivitis; OR gingival inflammation; AND essential oil; OR tea tree oil; OR Melaleuca alternifolia; AND chlorhexidine; AND reduction in gingival index; OR reduction in plaque index; OR reduction in bleeding from gums, in PubMed, Scopus, Proquest, Web of Science, EBSCO (dentistry and open access), Cochrane database, Clinical.gov.org and ctri.nic.in to search for relevant articles on 7 March 2021. Additionally, hand searching and snowballing were performed to identify relevant articles. The references in the included studies were checked for additional records. All published articles were included for screening. The grey literature (Google scholar) was also searched along with hand searching for relevant articles in the Journal of Periodontology, Journal of Clinical Periodontology, Journal of Periodontal Research, Journal of Dental Research. Open grey literature of any unpublished trials and registry of clinical trials (https://clinicaltrials.gov/) were searched for trial protocols.

Articles written in English were reviewed and included. Two reviewers (NS and LP) independently performed the searches in different databases. The initial check for the title and abstract screening followed by removal of duplicates in Mendeley Reference Manager (version 1.19.4) based on the following inclusion and exclusion criteria were performed.

Inclusion and exclusion criteria

Types of participants/disease

The studies conducted among patients aged between 12-75 years suffering from any of the periodontal diseases as classified by American Academy of Periodontology classification 1999 were included.16 Studies with systemically healthy patients without any medical or drug history were included.

Trials including participants without a baseline assessment and more than 50% of the patients who were lost to follow-up were excluded. Studies where patients reported the presence of any oral abusive habit, such as smoking, tobacco chewing or use of any form of tobacco, areca nut, or supari were excluded. Studies with participants undergoing chemotherapy or radiation therapy and pregnant and lactating people were excluded. All studies where TTO was used for the treatment of diseases other than periodontal disease were excluded.

Types of interventions

All patients where TTO was given as an adjunct to non-surgical periodontal therapy (scaling and root planing) were considered. TTO in any concentration and delivery systems were considered.

Type of comparator

CHX, in any concentration and form, prescribed for the treatment of periodontal disease was considered.

Types of outcome measures

The following primary and secondary outcomes were considered for inclusion:

  • Primary outcomes: clinical parameters such as plaque index,17 plaque surface score, gingival index (GI),17 bleeding index or bleeding as measured by % of sites with bleeding on probing (BOP) or bleeding scores and papillary bleeding index (PBI)18 were the primary outcomes considered

  • Secondary outcomes: dental staining, taste perception, gingival recession (in mm), periodontal inflamed surface area index (in mm2), alveolar bone loss (in mm or%) and radiographic changes (bone gain in mm or%) were considered.

Study design

All randomised, quasi-randomised and non-randomised clinical trials evaluating the efficacy of TTO compared to CHX were included. We considered studies with a minimum follow-up of 14 days from the start of the intervention or randomisation.

All in vitro and animal studies, letters to editors and commentaries and narrative and systematic review articles were excluded. Any study where TTO was not compared to CHX was excluded.

Data collection and analysis

Selection of studies

The results of the searches run on different databases were compiled in the Mendeley Reference Manager (version 1.19.4) and duplicates were removed. For those articles that fulfiled the eligibility criteria, the full articles were retrieved. A sample (that is, 20%) of the retrieved articles was screened by another team member (MK) to ensure a consistent application of the eligibility criteria. Any disagreements were mutually discussed between the two reviewers (NS and LP) and a consensus was reached by arbitration by the third reviewer (MK) if required. The process of study selection is reported using the PRISMA flowchart (Fig. 2).

Fig. 2
figure 2

PRISMA flow chart

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Data extraction and management

Data extraction was performed on a pilot-tested spreadsheet by two authors (NS and LP) independently. The following data was captured: author details; journal; country of origin; methodology of the study; sample size; type of periodontal disease and its diagnostic criteria; characteristics of the study population; nature of intervention and comparator group; method of randomisation; allocation concealment; blinding; number of follow-up/recall visits; and primary and secondary outcomes. All the data collected was switched among reviewers to check for any discrepancy. In case of any discrepancy, a third reviewer (MK) was consulted and final data was recorded after mutual consensus (Table 1). One reviewer (LP) transferred the data into the Review Manager 5.4 (Review Manager 2020) file.

Table 1 Characteristics of included studies
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Assessment of risk of bias in included studies

Two review authors (MK and LP) independently assessed the risk-of-bias (RoB) for each study according to the Cochrane risk-of-bias tool (RoB2).19 Any disagreement was resolved by involving another review author (VR). RoB was done within and across studies. In the assessment of the RoB, a score of low, high, or unclear was assigned for each included study. The overall quality of each study was then assessed by grading the seven bias categories.20

Data synthesis

While the risk of bias was minimal within and across the studies, a quantitative synthesis could not be performed due to the following conditions:

  1. 1.

    The total number of studies were only four. Among them, one study expressed the results in the form of a figure and did not explicitly mention the outcome values. Attempts to contact the author of the study failed

  2. 2.

    Of the three studies, there was considerable clinical heterogeneity, especially with regard to the variation in the concentration of intervention and age group of participants included

  3. 3.

    Methodological heterogeneity was also observed in view of the differences in the time points of outcome measurements and index used to measure outcomes.

As the heterogeneity could consequently contribute to statistical heterogeneity and compromise the validity of the results, a meta-analysis was not performed.

Results

Studies included

A total of 3,169 articles were obtained after searching Pubmed, Cochrane, Web of Science, Scopus and Google Scholar. References of review articles were checked and an additional nine articles were screened. After duplicate removal, 2,089 articles were selected for title and abstract screening, following which 12 articles were selected for full-text screening. Eight articles were excluded (Fig. 2)21,22,23,24,25,26,27,28 and four articles29,30,31,32 were included (Fig. 2, Table 1). The inter-examiner reliability at the full-text screening was very high (kappa score = 1.00).

Study characteristics

The included articles were from Italy,30 Egypt,29 Australia31 and India.32 A total of 251 participants were included in this review. The sample sizes ranged from 4230 to 9032 participants. Computer-generated randomisation list,30 random number table29 and simple randomisation using the lottery method32 were the methods of randomisation. The follow-up in the included studies ranged from 14 days30 to six months.29 The age of the participants ranged from 12 years29,32 to 60 years.30

The effectiveness of TTO in dental plaque-induced gingivitis,30 moderate to severe plaque-induced gingivitis,31,32 patients who were treated with fixed orthodontic appliances in the upper and lower arches and suffered from chronic gingivitis29 was assessed. 100% tea tree oil mouthrinse diluted in 100 ml of water,30 2.5% TTO-containing gel,31 15 ml of 1% TTO mouthrinse twice daily for two minutes29 and 10 ml of 0.2% TTO mouthrinse32 were compared with 0.12% CHX mouthrinse,30 0.2% chlorhexidine gel,31 15 ml of 0.2% CHX mouthrinse twice daily for two minutes29and 10 ml of 0.12% CHX mouthrinse.32

Plaque index was noted in three of the included studies29,30,32 while plaque surface score was assessed in the one study;31 gingival index has been assessed in all included studies29,30,31,32 and papillary bleeding index has been considered in two of the studies.29,31Ainamo and Bay bleeding index has been used in the study by Ripari et al.30. The presence of dental dyschromia, taste perception and breath as perceived by the patient has been evaluated in the study by Ripari et al.30. Intensity stain index has been assessed by Elmehy et al.29 The detailed characteristics of the included studies are given in Table 1.

Quality (risk of bias) assessment within included studies

The RoB across studies and within studies is given in Figure 3 and Figure 4. High RoB has been noted in relation to blinding of participants and personnel in two of the studies.29,30 There is an unclear RoB in terms of allocation concealment,29,30,31,32 blinding of outcome assessment,29,30,31 random sequence generation31 and incomplete outcome data.31 Low RoB is seen with respect to random sequence generation,29,30,32 blinding of participants and personnel,31,32 blinding of outcome assessment,32 incomplete outcome data29,30,32 and selective reporting and other bias.29,30,31,32

Fig. 3
figure 3

Risk of bias graph

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Fig. 4
figure 4

Risk of bias summary

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Critical appraisal of the individual sources of evidence

Evaluating the results obtained in the included studies to assess whether TTO can be used as an alternative to CHX for controlling gingival inflammation (GI) has seen that GI changed from 2.36 ± 0.37 to 0.30 ± 0.13 in the TTO group at the end of six months and there was a statistically significant difference between the TTO group, CHX group and the scaling only group.29 A similar reduction in GI was observed in studies by Ripari et al.30and Reddy et al.,32 although the difference between TTO and CHX groups were not statistically significant.32 In the study by Soukoulis et al.,31 there was a greater reduction in GI in the CHX group as compared to TTO.

A baseline PBI of 2.91 ± 0.71 changed to 0.16 ± 0.11 with the use of TTO.29 The use of CHX resulted in a change from 2.72 ± 0.71 to 0.13 ± 0.10 at six months while scaling alone resulted in a change from 2.53 ± 0.67 to 0.55 ± 0.21. The difference between the three groups was statistically significant.29 The papillary bleeding index showed significant improvement in the TTO group as compared to the CHX and placebo groups.31The bleeding index assessed in the study by Ripari et al.30 was 4.22% at the recall visit in the TTO group as compared to 6.28% in the CHX group.

The use of TTO as an alternative to CHX for controlling biofilm formation has been assessed through evaluation of plaque index which showed a reduction from 53.25% to 5.5% in the TTO group and from 47.69% to 2.37% in the CHX group in the study by Ripari et al.30 and a similar result (1.67 ± 0.25 to 0.28 ± 0.21 in the CHX group as compared to TTO group with a reduction from 1.73 ± 0.22 to 0.43 ± 0.22) has been observed in the study by Elmehy et al.29 The plaque surface score assessed in the study by Soukoulis et al.31 also showed a comparable trend with better plaque reduction for the CHX group as compared to the TTO group. However, in the study by Reddy et al., reduction in plaque scores was 15.10% in the TTO group, 12.50% in the CHX group and 4.73% in the placebo group.32

The presence of dental staining, taste perception and breath alteration was evaluated in the study by Ripari et al.30 It was observed that TTO did not cause dental dyschromia and 4 out of 20 subjects complained of nausea. Staining was noticed in 20% of sites in the CHX group in the same study, along with alteration in taste buds when eating salted and spicy foods in four of the subjects. About 12 of the subjects did not like the taste of the mouthwash due to an unpleasant burning sensation.30 The intensity staining index assessed in the study by Elmehy et al. showed that TTO had a score of 0.15 ± 0.24 as compared to 2.00 ± 0.64 in the CHX group.

Discussion

This review shows that TTO has a beneficial effect on reducing gingival inflammation and the effect is equivalent to that of CHX, as shown by the improvement in the gingival index and bleeding indices in the studies.29,30,32 This could be attributed to the stimulation of human monocytes by TTO resulting in production of superoxide by the monocytes, which plays a microbicidal role.15 At the same time, chemical analysis of water-soluble components of TTO, terpinen-4-ol, a-terpineol and 1,8-cineole has shown that terpinen-4-ol suppressed N-formyl-methionyl-leucyl-phenylalanine (fMLP) and lipopolysaccharide (LPS) but not phorbol 12-myristate 13-acetate (PMA)-stimulated superoxide production, while a-terpineol effectively suppressed fMLP-, LPS- and PMA-stimulated superoxide production so that an excessive superoxide activity is inhibited.33 The antibacterial effect of the TTO has been postulated to result from its ability to disrupt the permeability barrier of the microbial membrane.15 This in turn results in the loss of membrane integrity and function with leeching of intracellular material and an inability to maintain microbial intracellular homeostasis.34 In the study by Soukalis et al., there was a greater reduction in GI in the CHX group as compared to the TTO group. This was the only study included in this review in which gel forms of both the agents have been used. In this study, 2.5% TTO has been compared with 0.2% CHX. It may be assumed from the findings of this study that 0.2% CHX is superior to 2.5% TTO in reducing the GI which is contradictory to the findings of the other included studies. However, a systematic review by Supranoto et al. has shown that CHX gel is inferior in its ability to control plaque as compared to CHX mouthrinse.35 Furthermore, in the study by Taalab et al. local delivery of 5% TTO gel has resulted in the improvement of pocket probing depth (PPD), clinical attachment loss (CAL), GI and BOP.36 The variation in the behaviour of the two agents in the included studies may be explained on the basis of the difference in the concentration of the agents used.

CHX has been found to be more effective than TTO in achieving plaque control.29,30,31 The efficacy of TTO as an antibacterial agent has been shown in several studies.15,34 Hence, the inferior anti-plaque activity of TTO as compared to CHX might be explained as due to a reduced substantivity or a reduction of its antibacterial properties in comparison to CHX once bounded to oral tissues.37 TTO has been shown to produce less staining29,30 and alteration in taste sensation as compared to CHX.30 Similar results have been observed in other studies.37

This review shows that the effect of TTO in reducing gingival inflammation is comparable to that of CHX but its ability to reduce plaque is less. The limitation of the review is that the strength of evidence obtained from this systematic review is based on the limited number of studies with wide clinical heterogeneity. The studies differed in the mode and dose of administration of CHX and TTO, outcome assessment using multiple indices and duration of follow-up visits. Periodontal disease parameters such as PPD and CAL have not been assessed in the included studies. Another limitation was that meta-analysis could not be conducted due to the considerable clinical and methodological heterogeneity. It is recommended that more standardised randomised controlled trials with definite diagnostic criteria for periodontal disease and uniform trial protocol for the administration of TTO and CHX may be conducted to support or refute the evidence on the use of TTO as a replacement for CHX in the management of periodontal diseases.

Conclusion

TTO as a replacement of CHX would be beneficial while considering the adverse effects of CHX on taste perception and staining of teeth. TTO can improve gingival inflammation, reduce BOP and control plaque. TTO is found to be superior to CHX in reducing signs of gingival inflammation elicited through indices such as GI and PBI; however, CHX is superior to TTO in inhibiting plaque formation, probably due to its increased substantivity. Thus, with existing evidence, it can be concluded TTO may be used as an alternative to CHX for reduction of gingival inflammation in conjunction with efficient plaque control measures.