Original Article

Clinical effectiveness of aloe vera gel as an adjunct to mechanical debridement in patients with periodontitis: A systematic review and meta-analysis

Introduction

Periodontitis is a globally prevalent oral disease affecting the periodontium. It presents with gingival inflammation, connective tissue degradation, and alveolar bone loss, eventually leading to tooth loss. The complex interaction between the pathobionts and the host immune response is responsible for the disease’s commencement and progression.^1,2

Periodontal treatment is primarily concerned with reducing the burden of pathogenic subgingival bacteria and resolving inflammation.^2-4 The initial step in periodontal treatment is the nonsurgical management, which consists of mechanical debridement, supra- and sub-gingival irrigation, and the use of additional chemotherapeutic agents.^2,3 Mechanical debridement refers to scaling and root planing (SRP), which is the elimination of supragingival and subgingival deposits using hand and/or power-driven instruments. Thus, SRP helps restore periodontal health by reducing microbial load.^2,5,6

Various treatment options are being used secondary to SRP, including systemic and locally applied antimicrobial agents, antiseptics, anti-inflammatory agents, and nonsurgical use of lasers.^5,7 These adjunctive aids enhance the effects of SRP and promote healing. Systemic and local antimicrobial agents have been widely used. However, these agents are associated with adverse effects like antimicrobial resistance, gastrointestinal intolerance, altered taste sensation, staining of teeth, and many more.^8-11 Recently, phytotherapeutic agents have garnered significant attention as supplementary treatments to nonsurgical periodontal therapy due to their positive qualities like availability, good patient tolerance, reduced cost, and reduced side effects.^8,12

Aloe vera, botanically known as Aloe barbadensis, is a highly valued medicinal plant from the family Liliaceae. It is widely recognized for its wound healing, anti-inflammatory, immunomodulatory, antimicrobial, and antioxidant properties. It also stimulates epithelial cell migration and collagen maturation, promoting tissue regeneration.^13,14 It is used to treat wounds, burns, skin disorders, infections, gastrointestinal disorders, hemorrhoids, hair loss, and sinusitis.^13,15,16 In dentistry, aloe vera is used as a topical applicant for oral lesions like aphthous ulcers, oral lichen planus, pemphigus, angular cheilitis, herpetic lesions, oral submucous fibrosis, traumatized tissues, on extraction sockets, chemical burns, in denture stomatitis and periodontally infected sites.^13,17

The pharmacological qualities of aloe vera make it valuable for the treatment of periodontitis.^13,14,17 When used as a mouthwash, aloe vera exhibits optimistic results in resolving gingival inflammation, with no documented side effects.¹⁵ In patients with periodontitis, subgingival placement of aloe vera gel or chip significantly improved clinical parameters.^5,13,18-20 Singh et al.²⁰ found a significantly higher level of antioxidant levels in GCF after applying aloe vera gel to periodontitis patients.

In today’s world, clinicians are expected to keep pace with advancements in knowledge and clinical practice. Evidence-based practice is the application of research findings into clinical practice. Considering the usefulness of aloe vera in treating periodontal diseases, the present systematic review/meta-analysis addresses the question, “What is the effectiveness of aloe vera gel used as an adjunct to mechanical debridement in the treatment of periodontitis, when compared to SRP alone or with placebo?”

Methods

Registration and protocol

The study protocol was registered at PROSPERO International Prospective Register of Systematic Reviews (ID: CRD42020201315). This systematic review and meta-analysis were prepared in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines²¹ and the Cochrane Handbook of Systematic Reviews and Interventions.²²

Focused question

The present study focuses on the question, “What is the effectiveness of aloe vera gel used as an adjunct to SRP in the treatment of periodontitis when compared to SRP alone or with a placebo?”

Eligibility criteria

A PICO-based search strategy was developed as follows.

Study characteristics in PICO format

Randomized controlled trials (RCTs) were included in this study.

Participants (P): Patients with periodontitis with a probing pocket depth (PPD) of 4‒8 mm

Intervention (I): Subgingival administration of aloe vera gel as an adjunct to SRP

Comparison (C): With SRP alone or with a placebo

Outcome (O): Plaque index (PI), gingival index (GI), PPD

Inclusion criteria

1. RCTs done on patients with periodontitis with a PPD of 4‒8 mm

2. RCTs done with aloe vera gel as an adjunct to SRP with 4‒6 weeks of follow-up

3. No restrictions on age and gender

4. Full-text articles

5. RCTs published until October 2024

6. Articles published in the English language

Exclusion criteria

1. Studies using aloe vera in any other form were not considered.

2. Non-randomized trials (controlled/uncontrolled), case series, case reports, descriptive and analytical studies, in vitro studies, animal studies, review papers, letters to the editor, monographs, and conference papers were excluded.

3. Literature in other languages that could not be translated by the reviewer was excluded.

4. Unpublished data with full access.

Information sources

An extensive electronic search was conducted on PubMed/MEDLINE, PubMed Central, OVID, Google Scholar, and Cochrane Library databases up to October 2024 to determine the eligible studies for this review. Further studies were found by hand-searching the reference lists of the selected papers.

Search terms used ( MeSH terms)

The search terms used to identify relevant articles were periodontitis, adult periodontitis, chronic periodontitis, aloe vera gel, aloe, scaling, dental, supragingival, supragingival scaling and root scaling, root planing, planing, nonsurgical periodontal therapy, local drug therapy, local drug delivery, local drug delivery (LDD), outcome, treatment, patient-relevant outcome, clinical effectiveness, treatment effectiveness, rehabilitation outcome, outcome, rehabilitation, effectiveness.

Study selection process

Two reviewers (NA and KV) independently examined the titles and abstracts of all studies during the preliminary round of study selection. A third author (RS) was brought in to settle the differences over the eligibility of the articles. Irrelevant studies were excluded. The full texts of the articles that met the inclusion criteria and the keywords were gathered. Further screening of the full texts of the selected articles was performed during the second round of the study selection. Articles that did not match the inclusion criteria were excluded from consideration, and the reasons for exclusion were noted (Table 1).

Data collection process and data items

Data from the chosen articles were collected by two reviewers (NA and KV) using data extraction forms, which included details like the details of the study, year of publication, study design, participants and grouping, intervention and comparison, number of applications of aloe vera gel, parameters assessed, follow-up, statistical analysis used, and outcome. A third reviewer (SK) settled the disagreements over the data to be extracted.

Risk of bias assessment

Two reviewers (NA and SS) used the ROB2.0 tool to evaluate the risk of bias in the included RCTs, adhering to the Revised Cochrane Risk of Bias guidelines.⁴² This instrument consists of five items, which include bias due to randomization, deviation from intended intervention, missing outcome data, measurement of the outcome, and selection of the reported result. The articles were deemed low risk if all the criteria were met, high risk if one or more criteria were not met, and some concerns of bias if one or more criteria were partly met or had insufficient information. Finally, the overall bias for each article was also assessed. Disagreements regarding the same were settled by a third reviewer (VKP).

Effect measures and synthesis of results

Data on the outcomes were extracted from each study and initially entered into Microsoft Excel. The statistical analysis was conducted using the licensed Review Manager version 5.4.1 [Review Manager ( RevMan ) [Computer program]. Version 5.4. The Cochrane Collaboration, 2020. The chi-squared test and I²test were used to calculate the heterogeneity between the studies. An inverse variance statistical method along with random effects analysis model was employed for an expected outcome of continuous data type, and the effects estimate measure was expressed as mean difference (MD) with totals, subtotals, and 95% confidence interval. The pooled effect measure (overall effect) was estimated using the Z test. The level of significance was determined at P ≤ 0.05. Forest plots and funnel plots were created for graphical presentations of results.

Results

Study selection

A total of 1727 articles were found in the search results (1709 from databases and 18 from additional sources). After removing duplicates, 1438 articles were screened for the titles and abstracts. Following screening, 1401 articles were eliminated, and 37 articles were retained. The full texts of these 37 articles were reviewed, and 22 articles were excluded. Finally, 15 articles were included in the systematic review.^{1,5,18,20,43-53} Out of these 15 articles, six articles^{18,45,48,50,51,53} were used for the meta-analysis of mean PI, two^49,51 were used for meta-analysis of mean change in PI, seven articles^{18,45,46,48,50,51,53} were used for the meta-analysis of mean GI, two^49,51 were used for meta-analysis of mean change in GI, and eight articles^{18,20,45,46,48,50,51,53} were used for meta-analysis of PPD (Figure 1). An overview of the articles that were excluded is provided in Table 1.

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Figure 1.

PRISMA flow diagram 2020. PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-analysis

Figure 1.

PRISMA flow diagram 2020. PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-analysis

Study characteristics

This study analyzed 15 RCTs.^{1,5,49–53,18,20,43-48} All these studies evaluated the clinical efficacy of subgingival placement of aloe vera gel as an adjunct to SRP in patients with periodontitis. Participants in the test group received SRP + aloe vera gel, whereas the control group received SRP or SRP plus a placebo gel. Table 2 presents the characteristics of the included studies. Out of 15 trials that were included, 11 trials reported a single application of aloe vera following SRP,^{1,5,53,18,20,43,45-47,51,52} while four reported multiple applications.^44,48-50 Two RCTs used Curagel (by Cure Pharma),^48,49 two RCTs used 98% aloe vera gel,^5,18 one RCT used 2.5% aloe vera gel,⁵¹ and one RCT used 99% aloe vera gel.⁴⁵ The follow-up time in all trials ranged from 3 weeks to 12 months.

Risk of bias assessment

The graphs for ROB2.0 were generated using Robvis.⁵⁴The domain-level judgments for each study in the Traffic light plot (Figure 2) showed that three studies had a low overall risk of bias, four studies had some concerns, and eight studies had a high overall risk of bias. The distribution of risk-of-bias judgments within each bias domain in the Summary bar plot (Figure 3) depicted a 20% low bias, 27% unclear bias, and 53% high overall risk of bias. The lowest risk was observed in the three main areas of conducting an RCT – missing outcome data (100%), deviations from intended interventions (67%), and randomization process (67%), thus assuring the strength of the methodology of the included studies. However, the highest risk was observed in the measurement outcome (48%) due to the inconsistencies in the measurement of the outcome variable using other indices and non-blinding of investigators

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Figure 2.

Traffic-light plot of ROB 2.0 assessment of the included studies

Figure 2.

Traffic-light plot of ROB 2.0 assessment of the included studies

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Figure 3.

Summary bar plot of ROB 2.0 assessment of the included studies

Figure 3.

Summary bar plot of ROB 2.0 assessment of the included studies

Meta-analysis of PI

Mean PI (random effects model)

The pooled MD in a random model analysis of PI on teeth at 4‒6 weeks post-intervention was -0.23 (pooled 95% CI: -0.69, 0.23; P = 0.33), favoring the experimental group. Out of the total 6 studies included in the meta-analysis of PI, three studies^45,48,50 showed MD of PI favoring the experimental group (aloe vera + SRP), two studies^18,53 showed no MD, and one study⁵¹ favored the control group (SRP alone), all with narrower 95% CI. The treatment (aloe vera adjunct to mechanical debridement) in periodontitis patients had a 50% effect on reducing PI scores in 4‒6 weeks. The I² statistic of PI on teeth post-intervention showed significant heterogeneity of 97% (Tau² = 0.31; χ² = 157.79, df = 5, P < 0.00001). The test for overall effect non-significantly favored the experimental group (Z = 0.98; P = 0.33) (Figure 4).

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Figure 4.

Forest plot of the mean plaque index

Figure 4.

Forest plot of the mean plaque index

Mean changes in PI (fixed effects model)

The fixed effects model showed an increased PI (MD = 0.12; 95% CI: 0.09, 0.15; P = 0.20, not significant) at 1 month, favoring the control group, with the I² statistic showing moderate heterogeneity (40%) (Figure 5).

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Figure 5.

Forest plot of mean changes in plaque index

Figure 5.

Forest plot of mean changes in plaque index

Meta-analysis of GI

Mean GI (random effects model)

A significant pooled mean difference in the GI of teeth post-intervention (4‒6 weeks) was observed in a random model analysis. The overall effect was -0.28 (pooled 95% CI: -0.51, -0.60), favoring the experimental group (Z = 2.48; P = 0.01). Among the 7 studies used for the meta-analysis of the GI, five studies^{45,46,48,50,51} favored the experimental group, and two studies^18,53 had no MD, with a considerably broader 95% CI compared to the PI analysis. The treatment for periodontitis patients using aloe vera as an adjunct to mechanical debridement showed a 71% effect on reduction in the GI scores in 4‒6 weeks. The heterogeneity test showed the I² statistic of the GI to be significant with 92% heterogeneity (Tau² = 0.07; χ² = 76.79, df = 6, P < 0.00001) (Figure 6).

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Figure 6.

Forest plot of the mean gingival index

Figure 6.

Forest plot of the mean gingival index

Mean changes in GI (fixed effects model)

The fixed effects model showed an increased GI (MD: 0.17; 95% CI: 0.12, 0.23; P = 0.00001, significant) at 1 month, favoring the control group, with the I² statistic showing zero heterogeneity (0%).

Meta-analysis of PPD

Mean PPD

A significant pooled mean difference in a random model analysis of PPD on teeth at 4‒6 weeks post-intervention was -0.45 (pooled 95% CI: -0.78, -0.11), favoring the experimental group (Z = 2.63; P = 0.009). Out of the total 8 studies included for the meta-analysis of PPD, seven studies^{20,45,46,48,50,51,53} showed MD of PPD, favoring the experimental group, and one study¹⁸ favored the control group, all with a broader 95% CI. The use of aloe vera and mechanical debridement in periodontitis patients showed an 88% effect in reducing the PPD levels after 4‒6 weeks. The I² statistic of PPD post-intervention showed a significant heterogeneity of 84% (Tau² = 0.16; χ² = 42.78, df = 7, P < 0.00001).

Mean change in PPD

Only one eligible study reported a significant mean change in PPD between the test and control groups; hence, a meta-analysis was not conducted.⁵¹

Publication bias

A funnel plot was prepared to assess the publication bias in all the studies included in the meta-analysis. The plotting consists of an effect estimate (mean difference) on the X-axis and a standard error of the mean difference on the Y-axis. Each circle represents the individual study effect estimate. Aggregation of individual study effect estimates was observed to coincide with the overall effect estimate line (middle line) and well within the 95% CI of the funnel, representing the majority of the larger precision studies on the top of the funnel as depicted in the GI and no publication bias. The funnel plots of PI and PPD had most of the studies plotted on the middle and lower section of the funnel, suggesting lower precision, indicating no publication bias in the current meta-analysis.

Discussion

Aloe vera is a medicinal plant renowned for its diverse therapeutic properties, including promoting wound healing, providing pain relief, reducing inflammation, and exhibiting antibacterial, antifungal, antiviral, antioxidant, and immunomodulatory properties.⁵⁵ It also offers protection against radiation-induced mucositis and lowers the likelihood of oral thrush in patients receiving radiotherapy.⁵⁶ Aloe vera has various applications due to its medicinal properties in periodontics. In 2014, Dhingra, in his systematic review, concluded that, although the studies included reported the aloe vera dentifrices to be equally effective as conventional dentifrices, the outcomes could not be conclusively reported due to the significant risk of bias of the studies.⁵⁷ Another systematic review by Al-Maweri et al¹⁵ stated that aloe vera mouthrinse was equally effective as chlorhexidine in minimizing gingival inflammation and less effective than chlorhexidine in minimizing plaque. Recently, Jadhav et al⁵⁸ reported that locally delivered aloe vera significantly improved periodontal parameters.

The current systematic review focuses on the question, “What is the clinical effectiveness of the subgingival application of aloe vera gel as an adjunct to SRP in the treatment of periodontitis?”

RCTs available on different databases until October 2024 were included in this review, as they are categorized as Level II evidence in the hierarchy. An extensive literature search was conducted, and 15 RCTs that fulfilled the eligibility criteria were chosen for this study.

The current systematic review summarizes the fifteen studies included; fourteen^{1,5,50-53,20,43-49} studies indicated that using aloe vera gel along with SRP proved to be advantageous in the treatment of periodontitis, whereas one study¹⁸ reported no difference between the two groups. Deepu et al⁵¹ found that aloe vera gel was effective in the short term (one-month follow-up) but had no effect in the long term (two-month and four-month follow-ups). There were no reported side effects from using aloe vera gel in any of these studies. In all these trials, aloe vera was injected into the periodontal pocket after SRP in the test group.

The primary outcomes assessed in this study were PI, GI, and PPD. This meta-analysis demonstrated that adjunctive use of aloe vera gel with SRP significantly enhanced PI, GI, and PPD in patients with periodontitis. The antiplaque activity of aloe vera can be credited to its antibacterial and antifungal action, especially against Streptococcus and Candida species.^15,59 Numerous pharmacologically active substances found in aloe species, including homonataloin, aloeresin, aloe emodin, aloin (the C-glucoside of aloe emodin), and chrysophanol, have all been linked to its antimicrobial activity.⁶⁰ The anti-gingivitis effect of aloe vera can be linked to its antiplaque and potent anti-inflammatory characteristics.¹⁵ Aloe extracts are effective against bradykinin, histidine, COX-1, and COX-2 enzymes.⁶⁰ Additionally, aloe vera includes elements that aid in forming collagen, including vitamin C, mannose-6-phosphate, dermatan sulfate, and hyaluronic acid, which reduce swelling and gingival bleeding.^15,59 Aloins can inhibit matrix metalloproteinases (MMPs) because they are structurally analogous to tetracyclines.⁶¹ Inhibition of MMP-2 and MMP-9 prevents tissue destruction in periodontitis.⁶² Furthermore, aloins inhibit collagenase activity and stimulate cell development, producing greater collagen content.⁶¹ As a result of these properties, aloe vera improves the PPD.

The meta-analysis of all three parameters revealed a sizable heterogeneity, which might be attributed to the limitations of clear evidence. Lack of standardization and intra-examiner calibration were noted in most of the studies included in this meta-analysis. Additionally, we encountered inconsistencies in the number of applications and the concentration of aloe vera gel used in these studies. Regrettably, no literature is available on the sustenance and half-life of aloe vera gel when placed in the periodontal pocket. Hence, the substantivity and bio-availability of aloe vera gel cannot be debated. However, Sethi et al¹⁸ proposed using a bio-adhesive compound with aloe vera gel to keep it in the periodontal pocket for a longer period for greater advantages. The use of aloe vera gel with different concentrations may also have influenced the results of this meta-analysis. Furthermore, as the included studies published their results in different formats, separate analyses were performed for studies with mean and standard deviation data and studies with mean change data. Also, inadequacy in the total number of studies included with language specificity (English) seems to be another drawback.

Conclusion

The findings of this study indicate that the adjunctive use of aloe vera gel effectively reduces PI, GI, and PPD in patients with periodontitis, with no adverse effects observed. Based on these results, it is recommended that future research include long-term clinical trials with standardized methodologies to provide more robust evidence on the efficacy of aloe vera gel in periodontal treatment.

Competing Interests

The authors declare that they have no competing interests.

Data Availability Statement

The study protocol, methodology, search terms used, and statistical analysis plan have been discussed in the manuscript.

Ethical Approval

Not applicable.

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