Myrrh in the Management of Periodontal Disease and Gingival Healing: A Systematic Review and Meta-Analysis

ABSTRACT

Aim:

Periodontal disease remains a prevalent chronic condition worldwide, and interest has grown in natural adjunctive agents such as Commiphora myrrh for their potential antimicrobial and healing properties. This systematic review evaluated the antimicrobial and clinical effects of myrrh in managing periodontal disease, gingival healing, and pathogen reduction across in vitro, animal, and clinical studies.

Methods:

A comprehensive search of major databases (2010–2025) was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, including randomized controlled trials (RCTs), in vitro, and animal studies. Primary outcomes were gingival and plaque indices, healing parameters (swelling, redness), and antimicrobial efficacy. Risk of bias was assessed using the Cochrane RoB 2, Systematic Review Center for Laboratory Animal Experimentation, and Quality Assessment Tool for in vitro Studies of Dental Materials, with meta-analyses performed for eligible RCTs, and certainty of evidence rated using the Grading of Recommendations Assessment, Development, and Evaluation approach.

Results:

Fifteen studies met the inclusion criteria: six in vitro, one animal study, and eight RCTs. In vitro studies consistently demonstrated strong antimicrobial effects of myrrh, particularly in its essential oil form, against periodontal pathogens and Staphylococcus aureus. The animal study indicated enhanced early wound healing, but also dose-dependent toxicity with prolonged use. Meta-analysis of RCTs revealed a small yet statistically significant reduction in plaque, whereas effects on gingival inflammation and healing were not significant. Reported adverse effects were minimal.

Conclusion:

Myrrh shows promising potential as an adjunct in periodontal therapy, supported by in vitro and preclinical findings; however, further well-designed, standardized clinical trials and translational animal studies are essential to confirm its efficacy.

INTRODUCTION

Periodontal disease, although preventable, remains one of the most common diseases affecting approximately 20%–50% of the population worldwide,[1] with an estimated 1 billion severe cases.[2] In Saudi Arabia, the prevalence of periodontal disease is estimated to be 51% of the population.[3]

Periodontal disease refers to the inflammatory condition that affects the periodontium, including the gingiva, periodontal ligament, cementum, and the alveolar bone. It initially begins as a reversible acute form, gingivitis, and progresses to a more destructive chronic inflammation, periodontitis, if left untreated.[4] It initially occurs via the dysbiosis of the normal oral flora to more harmful gram-negative bacteria, including Treponema denticola, Porphyromonas gingivalis, Tannerella forsythensis, known as the red complex, which are established periodontal pathogens.[5] Despite not being considered a key periodontal pathogen, few studies have isolated Staphylococcus aureus from periodontal pockets, oral mucosa, and subgingival biofilm, with prevalences of 10.8%, 19.6%, and 22%, respectively.[6,7] Furthermore, Veras et al.[8] found a moderate association between S. aureus and periodontitis, suggesting it to be a potential periodontal pathogen.

Management of periodontal disease begins with the non-surgical periodontal treatment, which is commonly followed by the adjunctive use of chlorhexidine mouthwash. Although it is considered a “Gold Standard” chemotherapeutic agent, chlorhexidine can lead to undesirable side effects such as taste alteration, mouth/tongue pain, xerostomia, and, commonly, teeth staining,[9] which may negatively affect patients’ compliance, drawing attention to exploring herbal derivatives as adjuncts such as myrrh.

Myrrh, known as “Commiphora myrrh,” is regarded as a medicinal plant that has been utilized throughout history and has been demonstrated to have potential anti-inflammatory and antimicrobial effects.[10] However, there is limited literature regarding the beneficial potential of myrrh in maintaining periodontal health. Therefore, this review aims to examine the clinical effects of myrrh in managing periodontal disease and promoting gingival healing.

MATERIALS AND METHODS

OBJECTIVES AND RESEARCH QUESTION (PICO)

The primary objective of this review is to examine the effects of myrrh in improving periodontal outcomes and/or gingival healing, including but not limited to Plaque Index (PI), Gingival Index (GI), and swelling, as well as the efficacy against the periodontal pathogens and S. aureus, as well as animal periodontal models. The secondary objective is to examine and document the adverse effects of myrrh.

The review question was as follows: In patients with periodontal disease (or experimental models), is myrrh therapy, compared with control or other interventions, effective in managing periodontal disease, promoting gingival healing, and pathogen reduction? PICO was as follows: P: Humans with gingivitis/periodontitis; animal models replicating periodontal infection; in vitro assays using isolated periodontal pathogens; I: Myrrh extract, preparation, or formulation; C: Placebo, control, or other interventions; O: Primary-changes in periodontal outcomes such as GI, PI, swelling, redness, bleeding, as well as pathogen reduction. Secondary: Examine and document adverse effects.

INCLUSION AND EXCLUSION CRITERIA

Inclusion criteria were peer-reviewed randomized controlled trials (RCTs), as well as animal and in vitro studies, that examined the effects of myrrh on periodontal parameters and gingival healing outcomes. Specific periodontal pathogens sought for the in vitro studies were the red complex, including P. gingivalis, T. denticola, and T. forsythia, in addition to S. aureus, which has been reported in elevated numbers in periodontal disease. Animal studies modeling periodontal disease were sought. Studies published in English and between 2010 and 2025 were included.

Publications that did not address periodontal or gingival outcomes, studies that combined myrrh with another active compound or intervention, and in vitro experiments that employed mixed microbial communities rather than isolated bacterial strains were excluded.

SEARCH TERMS AND STRATEGY

Combinations of terms, including Myrrh, Commiphora, Commiphora myrrh, Commiphora molmol, Commiphora erythraea, Myrrh Resin, Myrrh Oil, Bisabol Myrrh, Myrrh tree, and gingivitis, were used to search databases. Two investigators (JA and MA) screened the studies, while the third investigator (RTA) resolved any disputes that might have occurred. Gray literature was not included. The research strategy was adapted and modified based on the features and capabilities of each database. Table 1 presents the searched databases, along with their corresponding search strings or equations and applied filters.

Table 1.

Search strategy

Database	Search equation	Filters applied
CINAHL Ultimate	(TI myrrh OR TI commiphora OR TI Commiphora myrrh OR TI Commiphora molmol OR TI Commiphora erythraea OR TI Myrrh Resin OR TI Myrrh Oil)	Language: 2010–2025, English, full text, peer-reviewed journals
CENTRAL and Cochrane	“myrrh in Title Abstract Keyword OR Commiphora in Title Abstract Keyword OR Commiphora molmol in Title Abstract Keyword OR Myrrh Oil in Title Abstract Keyword OR Myrrh Resin in Title Abstract Keyword”	Year: 2010–2025
DOAJ	(Myrrh) OR (Commiphora)	None
Google Scholar	(“gingivitis” “Myrrh” OR “Commiphora” OR “Commiphora OR myrrh” OR “Commiphora OR molmol” OR “Commiphora OR erythraea” OR “Myrrh Resin” OR “Myrrh Oil” OR “Bisabol Myrrh” OR “Myrrh tree” OR “Holziana OR Myrrh”)	Title only, 2010–2015, English
Health & Medicine Gale	(Myrrh, Commiphora, Commiphora myrrh, Myrrh Resin) & (Commiphora molmol, Commiphora erythraea, Myrrh Oil) & (Bisabol Myrrh, Myrrh Tree)	2010–2025, English, peer-reviewed
MEDLINE Ultimate	(AB myrrh OR AB Commiphora myrrh OR AB Commiphora molmol OR AB Commiphora erythraea OR AB Myrrh Resin OR AB Myrrh Oil)	Last 15 years, peer-reviewed, full text, English
ProQuest	(abstract(myrrh) OR abstract(Commiphora) OR abstract(Commiphora myrrh) OR abstract(Commiphora molmol) OR abstract(Commiphora erythraea) OR abstract(Myrrh Resin) OR abstract(Myrrh Oil) OR abstract(Bisabol Myrrh) OR abstract(Myrrh tree) AND abstract(Holziana Myrrh))	January 1, 2010–January 15, 2025; source: EBM, scholarly journals; article types: article, review; full text; peer-reviewed; English
PubMed	(Myrrh or Commiphora or Commiphora myrrh or Commiphora molmol or Commiphora erythraea or Myrrh Resin or Myrrh Oil or Bisabol Myrrh or Myrrh tree or Holziana Myrrh and gingivitis)	Full text, English, exclude preprints, January 1, 2010–January 1, 2025
Science Direct	(Myrrh, Commiphora, Commiphora myrrh, Myrrh Resin) & (Commiphora molmol, Commiphora erythraea, Myrrh Oil) & (Bisabol Myrrh, Myrrh Tree)	Language: English, 2010–2025

ASSESSMENT OF STUDIES

The Quality Assessment Tool for in vitro Studies of Dental Materials (QUIN)[11] was utilized to assess the risk of bias for in vitro studies, Systematic Review Center for Laboratory Animal Experimentation (SYRCLE)[12] for animal studies, and the revised Cochrane Risk-of-Bias tool[13] for RCTs. Robvis tool was used to visualize the risk-of-bias assessment results.[14] Additionally, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach[15] and GRADEpro GDT[16] were used to assess and visualize the certainty of evidence.

DATA EXTRACTION AND STATISTICAL ANALYSIS

Excel software[17] was used for data extraction. Two investigators (SA and RA) extracted data, including author, year, study aims, sample size, measured outcome, interventions, follow-up period, results, drop-out rate, and adverse effects, if any, as well as study design-specific data, such as bacterial strains for in vitro studies.

For the statistical meta-analysis, only RCTs were included because of their clinical applicability, their capacity to establish causal relationships, and the validity and generalizability of their quantitative conclusions. The primary outcomes of interest included gingival inflammation and plaque accumulation, which were assessed across studies using GI, Modified Gingival Index (MGI), PI, and plaque control record (PCR), as well as swelling and gingival redness/color for gingival healing. Despite the difference in scale, GI (0–3) and MGI (0–4) were pooled together using the standardized mean difference (SMD), as they both quantify the severity and score of gingival inflammation in the same direction. However, PI (ordinal, 0–3) and PCR (percentage) were pooled separately due to the difference in units of measurement to avoid introducing substantial heterogeneity, which would compromise the validity of the analysis. For outcomes with less than three studies, a meta-analysis was conducted to provide a preliminary estimate of the effect.

Post-means, standard deviation (SD), sample number, and total events were extracted. In multi-arm (three-arm) studies, the sample size of the myrrh group was split between comparisons (i.e., ½ myrrh vs. control A and ½ myrrh vs. control B) to avoid double-counting and minimize unit-of-analysis errors in the pairwise meta-analysis. Meta-analyses were conducted using RevMan Web.[18] Each outcome was presented with its corresponding effect estimate, 95% confidence interval (CI), and statistical heterogeneity assessed using the I² statistic. An I² value greater than 50% indicated substantial heterogeneity. Subgroup analysis by factors such as comparator type, risk of bias, and follow-up interval was conducted to explore the potential sources of heterogeneity. To evaluate the robustness of the findings, sensitivity analyses were performed, which included the exclusion of outliers, small studies (n < 10), high-risk-of-bias studies, and MGI results for the gingival inflammation outcome. The clinical outlier threshold for the post-means was set to GI > 1.5 and PI > 2.0. Assessment of publication bias (funnel plot) was not performed due to the limited number of included studies per outcome in the meta-analysis (<10), which precludes meaningful funnel plot analysis.

RESULTS

The search yielded an initial record of 1534 articles. Among them, 1502 duplicate and ineligible articles were removed before screening. Out of the 32 screened records, 17 were excluded for multiple reasons, as shown in Figure 1, resulting in a final inclusion of 15 studies, eight of which were included in the meta-analysis. Six in vitro studies, one animal study, and eight RCTs were included.

Figure 1.

Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram illustrating the selection process of studies included in the systematic review

IN VITRO AND ANIMAL STUDIES

Among the six included in vitro studies, one evaluated myrrh’s activity against the red-complex organisms together with Aggregatibacter actinomycetemcomitans;[19] one focused solely on P. gingivalis;[20] and the remaining four examined its antimicrobial efficacy against S. aureus.[21,22,23,24]

Against periodontal pathogens, Saquib et al.[19] reported a 20 ± 0.55 mm zone of inhibition (ZOI) and a minimum inhibitory concentration (MIC) of 0.53 ± 0.24 mg mL⁻¹ for P. gingivalis, whereas T. forsythia exhibited the greatest resistance (ZOI = 13 ± 0.26 mm; MIC = 8.33 ± 3.61 mg mL⁻¹). Likewise, ALHarthi et al.[20] demonstrated sustained suppression of P. gingivalis, with ZOIs of 16–15 mm maintained over 72 h. For S. aureus, a 5% myrrh essential oil preparation achieved ≥99.999% killing within 2 h;[21] in contrast, a concentration-matched hexane fraction achieved only 40% killing. Alqahtani et al.[22] observed a 13 mm ZOI against S. aureus, while Lee et al.[23] recorded an 89% decrease in mature biofilm biomass with essential oil. Xiao et al.[24] further showed complete eradication of S. aureus after 5 days of exposure to 5% essential oil. These findings collectively confirm the potential and robust, yet formulation-dependent, bactericidal and anti-biofilm effects of myrrh against periodontal pathogens and S. aureus. Table 2 summarizes the characteristics of the in vitro studies.

Table 2.

Characteristics of in vitro studies

Author	Year	Bacterial strain of interest	Sample number	Myrrh-based interventions	Outcomes and methods	Myrrh-specific results
Saquib et al.	2021	Porphyromonas gingivalis, Treponema denticola, T. forsythia, Aggregatibacter actinomycetemcomitans	Triplicates discs per extract	Commiphora molmol (myrrh)	ZOI (disc diffusion), MIC, and MBC (broth)	P. gingivalis: ZOI: 20 ± 0.55 mm; MIC: 0.53 ± 0.24 mg/mL; MBC: 5.21 ± 1.81 mg/mL T. denticola: ZOI: 16 ± 0.55 mm; MIC: 2.56 ± 0.78 mg/mL; MBC: 20.83 ± 7.22 mg/mL T. forsythia: ZOI: 13 ± 0.26 mm; MIC: 8.33 ± 3.61 mg/mL; MBC: 78.33 ± 28.87 mg/mL A. actinomycetemcomitans: ZOI: 18 ± 0.1 mm; MIC: 2.08 ± 0.90 mg/mL; MBC: 20.83 ± 7.22 mg/mL
ALHarthi et al.	2021	P. gingivalis	4 plates × 4 groups	Myrrh solution	IZ (disc diffusion at 24/48/72 h	IZ: 24:16 mm, 48:15 mm, 72:15 mm
Khalil et al.	2020	Staphylococcus aureus	Triplicate cultures	5% myrrh hexane extract 5% myrrh essential oil	Time–kill CFU	2 h viable count, CFU/mL (% killing) 5% myrrh hexane extract: 3.0 × 107 (40.00%) 5% myrrh essential oil: 2.0 × 101 (>99.999%)
Alqahtani et al.	2024	Clinical S. aureus isolate	Not stated	Myrrh extract	ZOI (agar well)	ZOI: 13 mm vs. S. aureus
Lee et al.	2014	S. aureus	12 replicate wells per oil	Myrrh essential oil	Biofilm OD	Post-biofilm%: 11 ± 3
Xiao et al.	2020	Stationery S. aureus (CFU)	Triplicate tests	5% myrrh essential oil	CFU after 5 days	No obvious colonies grew on the TSB plate after drug exposure

ZOI = zone of inhibition, MIC = minimum inhibitory concentration, MBC = minimum bactericidal concentration, IZ = inhibition zone (synonymous with ZOI), CFU = colony-forming units, biofilm OD = optical density

The methodological quality of the six included in vitro studies was evaluated using the QUIN tool [Figure 2]. Three studies[19,23,24] were judged to have some concerns, while the remaining three[20,21,22] were rated as high risk of bias. Across all studies, consistent methodological issues were observed, particularly in domains related to internal validity, such as sample size/replicate calculations, randomization of experimental units, or blinding of operators, assessors, and analysts.

Figure 2.

Risk-of-bias assessment of included in vitro studies using the Quality Assessment Tool for in vitro Studies of Dental Materials

The results of the animal study[25] examining wound healing concluded that in the early healing phase, myrrh-treated wounds exhibited enhanced epithelial regeneration and angiogenesis compared to other groups. However, prolonged use beyond 2 weeks resulted in marked inflammation and tissue necrosis, suggesting dose-dependent toxicity. Additionally, myrrh reduced bacterial colonization and facilitated the earlier onset of wound remodeling. The quality of this study was assessed using the SYRCLE tool. While baseline characteristics were comparable and outcomes were fully reported, key methodological details were lacking; Randomization was mentioned but not described, and there was no evidence of allocation concealment or blinding of caregivers and outcome assessors. Additionally, the absence of dosing standardization raised concerns about performance bias. Overall, the study was judged to be at high risk of bias due to the lack of methodological safeguards in these key domains.

RANDOMIZED CONTROLLED TRIALS

Eight RCTs were included [Tables 3 and 4], with a total of 335 participants. Most trials assessed the effect of myrrh on gingival inflammation and plaque accumulation using indices such as PI, GI, MGI, and PCR,[26,27,28,29,30,31] while two studies[32,33] focused on gingival healing following surgical procedures. The majority compared myrrh to CHX or saline, and nearly all provided oral hygiene instruction and professional cleaning. Follow-up ranged from 48 h to 12 weeks. Only one study reported side effects of myrrh, including taste alteration (7%) and teeth staining (5%).[29]

Table 3.

Characteristics of randomized controlled trials

Author/s (year)	Sample size	Interventions and follow-up	Results	Drop-out rate	Adverse effects
Al-Zarea & Sghaireen (2020)	Initial total = 62 Myrrh = 32 CHX = 30 Analyzed = 62	Myrrh vs. 0.2% CHX Follow-up: 12 weeks	Reported as mean ± SD PI: myrrh (1.78 ± 0.81 → 0.32 ± 0.64) vs. CHX (1.86 ± 0.62 → 0.41 ± 0.36); final PI (P value): P = 0.50	0%	Side effects: No significant change in teeth and/or tongue stain
Bassiouny & Al-Barrak (2014)	Initial total = 30 Myrrh = 10 CHX = 10 Miswak = 10 Analyzed: 30	1% myrrh vs. 1% miswak vs. 0.2% CHX Follow-up: 3 weeks	Reported as mean ± SD PI: myrrh (0.93 ± 0.52 → 0.08 ± 0.09) vs. CHX (1.11 ± 0.41 → 0.24 ± 0.15) vs. miswak (1.07 ± 0.52 → 0.35 ± 0.25); final PI (P value): CHX vs. myrrh P = 0.01, CHX vs. miswak P = 0.26, myrrh vs. miswak P = 0.006 GI: myrrh (0.92 ± 0.40 → 0.19 ± 0.17) vs. CHX (1.03 ± 0.29 → 0.24 ± 0.18) vs. miswak (0.96 ± 0.45 → 0.28 ± 0.19); final GI (P value): CHX vs. myrrh P = 0.53, CHX vs. miswak P = 0.64, myrrh vs. miswak P = 0.28	Not reported/unknown	Side effects: not reported
Lenka et al. (2021)	Initial total = 40 Myrrh = 20 Placebo = 20 Analyzed = 30	Myrrh oil drops vs. placebo drops Follow-up: 48 h and 1 week	Reported as mean ± SD PI: myrrh (3.10 ± 0.39 → 2.34 ± 0.18) vs. placebo (3.27 ± 0.40 → 2.41 ± 0.25); final PI (P value): P = 0.37 GI: myrrh (1.94 ± 0.34 → 0.93 ± 0.33) vs. placebo (1.86 ± 0.31 → 1.03 ± 0.44); final GI (P value): P = 0.39	25% (five each group)	Side effects: none
Al-Eid (2019)	Initial total = 44 Myrrh = 22 Saline = 22 Analyzed: 40	Myrrh vs. saline mouthwashes Follow-up: 1 week	Binary reporting percentage (absence/presence) Color/redness: myrrh (85%/15%) vs. saline (60%/40%). P = not significant Swelling: myrrh (100%/0%) vs. saline (65%/35%). P < 0.001	9% (two each group)	Side effects: none

PI = Plaque Index, CHX = chlorhexidine, GI = Gingival Index, SD = standard deviation

Table 4.

Characteristics of randomized controlled trials

Author/s (year)	Sample size	Interventions and follow-up	Results	Drop-out rate	Adverse effects
Alotaibi et al. (2020)	Initial total = 75 Myrrh = 45 CHX = 30 Analyzed: 75	Myrrh vs. 0.2% CHX mouthwashes Follow-up: 2 weeks	Reported as mean ± SD for GI and percentage for PCR PCR: myrrh (81.6 ± 23.5% → 24.2 ± 22.1%) vs. CHX (65 ± 30.7% → 13 ± 21.2%); final PCR (P value): P = 0.03 GI: myrrh (1.3 ± 0.5 → 0.3 ± 0.38) vs. CHX (1.2 ± 0.5 → 0.11 ± 0.27); final GI (P value): P = 0.01	12% (six myrrh group and three CHX group)	Taste alteration%: myrrh: 7% vs. CHX: 100%; burning%: myrrh: 0% vs. CHX: 40%; staining%: myrrh: 5% vs. CHX: 30%
Ibraheem et al. (2022)	Initial total = 40 Myrrh = 20 CHX = 20 Analyzed: 35	1% myrrh vs. 0.12% CHX Follow-up: 1 week	Binary reporting percentage (absence/presence) Color/redness: myrrh (15/3) vs. CHX (17/0). P = 0.032 Swelling: myrrh (17/1) vs. CHX (17/0). P = 0.0632	12.5% (two myrrh group and three CHX group)	Side effects: not reported
Zahid & Alblowi (2019)	Initial total = 20 Initial myrrh = unknown Initial CHX = unknown Initial Saline = unknown Analyzed = 12	1% myrrh vs. 0.2% CHX vs. saline Follow-up: 2 weeks	Reported as mean ± SD PI: myrrh (0.88 ± 0.15 → 0.43 ± 0.27) vs. CHX (0.94 ± 0.06 → 0.72 ± 0.30) vs. saline (0.59 ± 0.33 → 0.70 ± 0.38); final PI (P value): saline vs. CHX vs. myrrh P = 0.40 GI: myrrh (0.39 ± 0.37 → 0.07 ± 0.06 vs. CHX (0.52 ± 0.34 → 0.36 ± 0.27) vs. saline (0.25 ± 0.12 → 0.18 ± 0.08); final GI (P value): saline vs. CHX vs. myrrh P = 0.11	40% (8)	Side effects: not reported
Zahid & Khan (2022)	Initial total = 24 Myrrh = 8 CHX = 8 Saline = 8 Analyzed = 19	1% myrrh vs. 0.2% CHX vs. saline Follow-up: 2 weeks	Reported as mean ± SD PCR: myrrh (74.46 ± 34.71 → 65.62 ± 31.83) vs. CHX (73.37 ± 33.3 → 86.56 ± 19.03) vs. saline (88.23 ± 28.36 → 67.44 ± 39.18); Final PCR (P value): saline vs. CHX (P = 0.912); saline vs. myrrh (P = 1); CHX vs. myrrh (P = 0.735) MGI: myrrh (3.68 ± 1.18 → 2.79 ± 0.8 vs. CHX (3.5 ± 0.3 → 3.05 ± 0.53) vs. saline (3.45 ± 0.96 → 3.91 ± 0.46); final MGI (P value): saline vs. CHX (P = 0.09); saline vs. myrrh (P = 0.016); CHX vs. myrrh (P = 1)	21% (one myrrh group, two CHX groups, two saline groups)	Side effects: not reported

PI = Plaque Index, CHX = chlorhexidine, GI = Gingival Index, PCR = plaque control record, MGI = Modified Gingival Index, SD = standard deviation

Post-treatment values (mean ± SD) of myrrh across studies demonstrated considerable variability. PI ranged from 0.08 ± 0.09 to 2.34 ± 0.18, while GI scores ranged from 0.07 ± 0.06 to 0.93 ± 0.33. The MGI, reported in one study, ranged from 3.68 ± 1.18 to 2.79 ± 0.8. For percentage-based outcomes, the PCR ranged between 24.2 ± 22.1% and 65.62 ± 31.83%. Postoperative soft tissue redness (color change) and swelling absence rates in the myrrh groups ranged from 83% to 85% and 94% to 100%, respectively.

Overall, the methodological quality was moderate [Figure 3]; only one study was rated as having a low risk of bias,[32] while most studies had some concerns, particularly regarding assessor blinding. Two studies were judged to have a high risk of bias due to poor reporting of allocation and detection procedures.[27,29]

Figure 3.

Risk-of-bias assessment of randomized controlled trials using the Cochrane RoB 2.0 tool

STATISTICAL ANALYSIS (RANDOMIZED CONTROLLED TRIALS)

Gingival inflammation (Gingival Index/Modified Gingival Index)

The overall meta-analysis [Figure 4A] showed no significant effect of myrrh on gingival inflammation (SMD: −0.29; 95% CI: −0.81 to 0.23; I² = 46%; P = 0.28). Sensitivity analyses using non-splitting approaches produced results consistent with the main analysis. Despite higher heterogeneity in non-CHX comparisons, effect direction and significance remained stable, suggesting the splitting method did not materially affect the findings [Figure 4B and C]. Subgroup analysis [Figure 5A–D] revealed minor differences: studies using the GI showed minimal effects (SMD: −0.12; 95% CI: −0.65 to 0.41; I² = 42%; P = 0.13), while the single MGI study showed a larger, but still non-significant, effect (SMD: −0.91; 95% CI: −2.21 to 0.40; P = 0.22). Myrrh appeared more effective compared to saline/placebo (SMD: −0.71; 95% CI: −1.62 to 0.19; I² = 27%; P = 0.12) but showed no difference vs. chlorhexidine (SMD: 0.04; 95% CI: −0.61 to 0.70; I² = 38%; P = 0.90) or miswak (SMD: −0.46; 95% CI: −1.55 to 0.63; I² = N/A; P = 0.41). Longer follow-up (2–3 weeks) (SMD: −0.36; 95% CI: −1.01 to 0.29; I² = 51%) and moderate-risk studies showed slightly greater effects (SMD: −0.54; 95% CI: −1.08 to 0.01; I² = 0%), but none were statistically significant.

Figure 4.

Overall effect of myrrh on gingival inflammation: (A) including three-arm studies by splitting n of myrrh groups, (B and C) no-splitting by including only two arms from the multiple arm studies (myrrh vs. chlorhexidine, myrrh vs. saline/miswak)

Figure 5.

Subgroup analysis of the effect of myrrh on gingival inflammation, Gingival Index/Modified Gingival Index (GI/MGI): (A) outcome assessment tool, (B) type of comparator subgroup analysis of the effect of myrrh on gingival inflammation (GI/MGI), (C) follow-up duration, and (D) risk-of-bias level

Sensitivity analyses [Figure 6] showed that excluding the MGI-based study resulted in a slight reduction in the overall effect estimate (SMD: −0.29 to −0.12) and a marginal decrease in heterogeneity (I²: 46% to 42%). While this suggests that the MGI data influenced the pooled results to some extent, it did not substantially alter the treatment efficacy. In contrast, the exclusion of small studies had a more pronounced effect. The overall effect size shifted from SMD: −0.29 to 0.02, reversing direction and eliminating the apparent benefit of myrrh. This indicates that smaller studies may have disproportionately affected the pooled estimates. Excluding studies at high risk of bias yielded the opposite outcome. The pooled SMD became more favorable (−0.29 to −0.54), and heterogeneity was eliminated (I² = 0%), suggesting that lower-quality studies may have attenuated the effect size and contributed to variability. Overall, slightly greater effects, though not statistically significant, were observed in moderate-risk trials.

Figure 6.

Sensitivity analysis of the effect of myrrh on gingival inflammation: (A) exclusion of studies using the Modified Gingival Index (MGI), (B) exclusion of small-sample studies, and (C) exclusion of studies with high risk of bias

PLAQUE ACCUMULATION (PLAQUE INDEX/PLAQUE CONTROL RECORD)

The meta-analysis of studies reporting PI demonstrated a statistically significant reduction in plaque accumulation favoring myrrh, with a mean difference of −0.16 (95% CI: −0.24 to −0.08; P < 0.0001) and no observed heterogeneity (I² = 0%) [Figure 7A]. Sensitivity analyses for plaque accumulation, using non-splitting methods [Figure 7B and C], showed comparable effect directions and overlapping CIs. Slightly higher heterogeneity was observed, but the splitting method did not appear to materially influence the results. Comparator subgroup analysis revealed the most substantial effect compared to miswak (MD: −0.27; 95% CI: −0.44 to −0.10; I²= N/A; P = 0.002) and a significant benefit over chlorhexidine (MD: −0.15; 95% CI: −0.26 to −0.05; I²= 0; P = 0.005) [Figure 8A]. The effect of the treatment vs. saline/placebo was not significant. Myrrh showed no benefit at 1 week but a significant effect at 2–3 weeks (MD: −0.20; 95% CI: −0.30 to −0.11; I² = 0%, P < 0.0001) [Figure 8B]. Overall, results consistently favored myrrh, with no heterogeneity across comparisons.

Figure 7.

Effect of myrrh on plaque accumulation measured by the Plaque Index (PI): (A) including three-arm studies by splitting n of myrrh group, (B and C) no-splitting by including only two arms from the multiple arm studies (myrrh vs. CHX, myrrh vs. saline/miswak)

Figure 8.

Subgroup analysis of the effect of myrrh on plaque accumulation measured by the Plaque Index (PI): (A) type of comparator and (B) follow-up duration

The pooled analysis of studies reporting PCR% outcomes [Figure 9] revealed no statistically significant difference between the myrrh and control groups (MD: 2.03; 95% CI: −17.87 to 21.92; P = 0.84; I² = 38%). The wide CI indicates substantial uncertainty and limited precision, likely attributable to small sample sizes and imbalance across baseline PCR values. Overall, the inconclusive effect of myrrh on plaque coverage, as measured by PCR%, could be determined.

Figure 9.

Overall effect of myrrh on plaque accumulation measured by the plaque control record (PCR)

To assess the robustness of the pooled effect on plaque accumulation (PI), sensitivity analyses showed that excluding the outlier study[28] [Figure 10A] slightly strengthened the effect estimate (MD: −0.16 to −0.19; 95% CI: −0.28 to −0.10) without altering heterogeneity (I² = 0%), indicating the result’s stability. Furthermore, excluding the small-sample study[30] [Figure 10B] yielded a comparable effect size (MD: −0.16 to −0.15; 95% CI: −0.23 to −0.07) with minimal heterogeneity (I² = 2%), suggesting that small-study bias had little influence. However, the exclusion of the high-risk-of-bias study[27] [Figure 10C] attenuated the effect and rendered it non-significant (MD: −0.16 to −0.10; 95% CI: −0.23 to 0.02), although heterogeneity remained absent (I² = 0%). This suggests that the observed benefit may be partially driven by lower-quality evidence. Overall, the PI outcome demonstrates stability against outlier and small-sample influences but remains sensitive to study quality, highlighting the importance of methodological rigor in evaluating treatment effectiveness.

Figure 10.

Sensitivity analyses for plaque accumulation (Plaque Index): (A) excluding outlier studies, (B) excluding small-sample studies, and (C) excluding studies with a high risk of bias

GINGIVAL HEALING (GINGIVAL COLOR/REDNESS AND SWELLING)

Two studies reported binary outcomes for post-surgical gingival healing, evaluating the presence or absence of color and redness changes, as well as swelling. The pooled analysis for color/redness improvement [Figure 11A] showed no significant difference between the myrrh and control groups (Risk Ratio [RR]: 1.06; 95% CI: 0.64 to 1.77; P = 0.82), with substantial heterogeneity (I² = 80%). Similarly, the pooled estimate for swelling reduction [Figure 11B] was non-significant (RR: 1.17; 95% CI: 0.74 to 1.86; P = 0.50), accompanied by considerable heterogeneity (I² = 85%). An overall inconclusive effect of myrrh on promoting gingival healing could be observed, likely due to the small sample sizes and high heterogeneity.

Figure 11.

Overall effect of myrrh on gingival healing: (A) color/redness improvement and (B) reduction of swelling

DISCUSSION

This review synthesized evidence from in vitro studies and RCTs evaluating the antimicrobial efficacy and clinical outcomes associated with myrrh in the management of periodontal disease. While the findings suggest promising in vitro antibacterial activity, the clinical evidence remains inconclusive, primarily due to methodological limitations and heterogeneity across studies.

The in vitro investigations consistently demonstrated potent antimicrobial effects of myrrh, particularly in essential oil formulations. Notably, significant inhibition of P. gingivalis and complete eradication of S. aureus were observed in multiple studies. These effects were markedly dependent on the formulation and concentration of myrrh, with essential oils outperforming crude and hexane extracts. Additionally, some studies have reported the potential efficacy of myrrh against endodontic pathogens.[34,35] In the animal model, myrrh demonstrated notable short-term wound healing potential, likely attributable to its antimicrobial and immunomodulatory properties. However, prolonged or high-concentration exposure resulted in excessive inflammation and tissue damage, indicating a dose- and duration-dependent response, which underscores the importance of controlled dosing and limited application duration for the therapeutic use of myrrh.

The mechanism of action of myrrh as an antibacterial and anti-inflammatory agent involves the orchestration of complex immune-regulatory pathways through suppression of pro-inflammatory mediators[36,37] and modulation of MAPK (Mitogen-Activated Protein Kinase) signaling pathways.[38]

In clinical trials, the effect of myrrh on gingival inflammation was not statistically significant. Although subgroup analyses suggested greater effects in studies of moderate methodological quality and those with more extended follow-up periods, these findings did not reach statistical significance. Conversely, myrrh demonstrated a small but statistically significant effect in reducing plaque accumulation with consistent findings across subgroups and sensitivity analyses. However, this effect was attenuated when high-risk studies were excluded, suggesting possible overestimation in lower-quality trials. The effects of myrrh on gingival healing, as assessed through redness and swelling, were inconclusive. The limited number of studies and small sample sizes precluded the drawing of robust conclusions regarding its efficacy in post-surgical healing contexts. Similarly, no significant effect was observed in the included percentage-based plaque measures (PCR%), highlighting the need for standardized outcome assessment.

Adverse effects were infrequently reported, with only one study noting mild taste alteration and teeth staining.[29] Although this suggests a favorable safety profile, there is limited confidence regarding the systemic safety of prolonged myrrh use. However, hypersensitivity reactions to myrrh have been reported, including allergic contact dermatitis[39,40] and a delayed skin reaction after oral ingestion of a myrrh-containing remedy.[41] Furthermore, it is suggested that excessive use of myrrh might be associated with acute abdominal discomfort, an increased risk of infertility, and miscarriage,[42] rendering it contraindicated during pregnancy.

The overall certainty of evidence [Figure 12] for myrrh’s effectiveness in periodontal care is moderate to very low, due to small sample sizes, methodological limitations, and inconsistent outcome measures. In vitro studies suggest antimicrobial potential but lack translational rigor. The included animal study supports short-term healing effects but revealed dose-dependent toxicity with prolonged use. Clinical trials show minimal or uncertain benefits for gingival inflammation, plaque control, and healing. This review is limited by the small number of high-quality RCTs and the absence of standardized outcome measures across studies. The inclusion of in vitro and animal studies, while informative, may limit generalizability to clinical settings. Publication bias could not be formally assessed due to the limited number of included studies. Future clinical trials should prioritize standardized formulations, outcome measures, rigorous methodological practices, and long-term follow-up, while in vitro studies should adopt uniform concentration and dosing protocols to enable meta-analytical integration; additionally, well-designed animal studies using standardized models are needed to bridge preclinical and clinical evidence.

Figure 12.

Summary of the overall certainty of evidence for the outcomes assessed, evaluated using the GRADE approach

CONCLUSION

In conclusion, this systematic review highlights the potential antimicrobial and clinical benefits of myrrh in periodontal therapy, particularly in reducing plaque accumulation and supporting early wound healing. While in vitro and animal studies have demonstrated promising antibacterial and immunomodulatory effects, the overall certainty of the evidence remains low due to methodological limitations, small sample sizes, and a lack of standardized outcomes. Clinical trials have yielded inconsistent findings regarding gingival inflammation and healing. Although short-term use of myrrh appears safe, only a few studies reported adverse events, which might be due to underreporting or short follow-up rather than actual safety, which warrants further caution regarding concerns about dose-dependent toxicity and hypersensitivity reactions. Future research should focus on well-designed trials with standardized formulations, rigorous methodology, and translational animal models to better establish the therapeutic role of myrrh in periodontal care.

CONFLICTS OF INTEREST

There are no conflicts of interest.

ETHICAL POLICY AND INSTITUTIONAL REVIEW BOARD STATEMENT

This study was approved by the Medical Ethics and Research Committee – Royal Commission Medical Center, Yanbu, Saudi Arabia. (No: RCYMC-EA-2023-01). Also, this study was registered with PROSPERO (CRD420251051656).

PATIENT DECLARATION OF CONSENT

Not applicable.

AUTHOR CONTRIBUTIONS

R.A. contributed to the study conception, data collection, data analysis, data interpretation, and manuscript writing. S.A. contributed to the study conception, data collection, analysis, data interpretation, and manuscript writing. J.A. contributed to the study conception, data collection, data analysis, data interpretation, and manuscript writing. M.A. contributed to the study conception, data collection, data analysis, data interpretation, and manuscript writing. R.T.A. contributed to the study conception, data collection, data analysis, data interpretation, and manuscript writing. Y.S. contributed to the study conception, data collection, data analysis, data interpretation, and manuscript writing. K.A. contributed to the study conception, data collection, data analysis, data interpretation, and manuscript writing. T.B. contributed to the study conception, data collection, data analysis, data interpretation, manuscript writing, and supervision. All authors reviewed and approved the final version of the manuscript for publication.

DATA AVAILABILITY STATEMENT

The original contributions presented in this study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.

LIST OF ABBREVIATIONS

• CHX: Chlorhexidine; CI: Confidence Interval; GI: Gingival Index; GRADE: Grading of Recommendations Assessment, Development and Evaluation; MAPK: Mitogen-Activated Protein Kinase; MGI: Modified Gingival Index; MIC: Minimum Inhibitory Concentration; PCR: Plaque Control Record; PI: Plaque Index; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses; QUIN: Quality Assessment Tool for in vitro Studies of Dental Materials; RCTs: Randomized Controlled Trials; Rob.2: Revised Cochrane Risk of-Bias Tool for Randomized Trials; RR: Risk Ratio; SD: Standard Deviation; SMD: Standardized Mean Difference; SYRCLE: Systematic Review Center for Laboratory Animal Experimentation; ZOI: Zone of Inhibition.

Funding Statement

The project was funded by KAU Endowment (WAQF) at King Abdulaziz University, Jeddah, Saudi Arabia. The authors, therefore, acknowledge with thanks WAQF and the Deanship of Scientific Research for technical and financial support.