The impact of electronic cigarette use on periodontitis and periodontal outcomes: a systematic review and meta-analysis
Periodontitis, a prevalent inflammatory condition affecting the supporting structures of the teeth, leads to the progressive destruction of the periodontal ligament and alveolar bone with increasing age, if not adequately managed . This multifactorial disease is primarily initiated by the microbial biofilms adhering to the tooth surface, yet it is also significantly influenced by a myriad of other risk factors, including genetics, systemic health, and lifestyle choices such as smoking. The Global Burden of Disease Study identifies severe periodontitis as the sixth-most prevalent condition worldwide, making it a major public health issue due to its high prevalence and its role in tooth loss and systemic health problems including cardiovascular diseases and diabetes. Traditional smoking has been well-documented as a critical risk factor for periodontitis, exacerbating both its prevalence and severity . It impacts oral health through several mechanisms: impairment of immune responses, alteration of the oral microbiota, and detrimental effects on the healing capacity of periodontal tissues . In response to the global shift in smoking trends, electronic cigarettes (e-cigarettes) have emerged as a popular alternative to traditional tobacco products . Marketed as a safer option, e-cigarettes are purported to offer the nicotine fix associated with conventional cigarettes but with fewer harmful constituents . E-cigarettes are devices that heat a liquid typically comprising propylene glycol, glycerin, nicotine, and flavorings into an aerosol that the user inhales . Since their introduction to the market in the early 2000s, e-cigarettes have triggered substantial public and scientific debate regarding their safety profile and health implications. Initially considered as a potential tool for smoking cessation, concerns have been raised about their addictiveness, particularly among younger populations, and their long-term health effects . The relationship between e-cigarette use and periodontal health is a subject of emerging interest within dental research. Unlike traditional cigarettes, the vapor from e-cigarettes contains fewer tar and carcinogens, suggesting a potentially lower risk of periodontal harm . However, the presence of nicotine, which is known to reduce blood flow and affect tissue oxygenation, remains a concern. Nicotine has been shown to alter periodontal fibroblast function, promote inflammatory responses, and increase the production of pro-inflammatory cytokines and matrix metalloproteinases, which are implicated in the degradation of periodontal tissues. Scientific inquiry into the effects of e-cigarettes on periodontal health is crucial as it could redefine preventive strategies and influence public health policies regarding the regulation and consumption of these devices. Most of the existing literature has focused on the general health impacts of e-cigarettes, with less emphasis on specific oral health outcomes. A previous meta-analysis concluded that e-cigarettes are a safer option than conventional tobacco cigarettes for oral health. However, the effect of e-cigarettes is not fully understood when compared to non-users, never-users, or non-smokers. Many recent studies show various effects . Furthermore, the research that does exist presents a mixed picture, likely due to variations in study design, population demographics, and the type of e-cigarette products used. Given this backdrop, an updated systematic review and meta-analysis are timely to synthesize existing data and provide a clearer understanding of the association between e-cigarette use and periodontal outcomes. This work aimed to critically evaluate the evidence on the impact of e-cigarette use on periodontitis and other periodontal outcomes. 

The study has been reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines . A protocol has been registered in PROSPERO: CRD42024565956. A semi-automated software (Nested-Knowledge, MN, USA) was used for the review. Search strategy A comprehensive literature search was conducted across several electronic databases including PubMed, EMBASE, and Web of Science. The search was performed from inception of each database up to up to June 15, 2024. No filters were imposed on the basis of type of article or language in the search. The keywords used in the search were combinations of: “electronic cigarettes,” “periodontitis,” and other keywords related to periodontal outcomes. Boolean operators (AND, OR) were used to combine the search terms. A detailed search strategy is presented in Table S2. Inclusion and exclusion criteria The systematic review incorporated studies that specifically examined the effects of e-cigarette use on various periodontal outcomes. Eligible studies were required to assess outcomes such as risk for periodontitis, bleeding on probing, probing depth, plaque index, medial bone loss, distal bone loss, and clinical attachment loss. Comparison group involved E-cigarette never users or non-users as reported by studies. Due to inconsistencies in the classification of e-cigarette users across the included studies, we used ‘never users’ and ‘non-users’ interchangeably as the comparison group, based on the terminology provided in each study. This represents a minor deviation from our original protocol. This review considered observational studies, including cohort, case-control, and cross-sectional designs, as well as clinical trials, to capture a broad range of evidence. On the other hand, certain types of publications were excluded from the review to maintain a focus on relevant and high-quality data. Excluded were studies that did not offer specific data on periodontal outcomes, ensuring that the review remained focused on the primary interest area. Additionally, case reports, editorials, and review articles were omitted, as these typically do not present original research data. Animal studies were also excluded, aligning the review strictly with human research. Studies available in English language only were included. Screening Following the initial search, all identified records were collated and uploaded into a the Nested-Knowledge platform to manage and track the screening process. The screening was conducted in two stages to efficiently filter the relevant studies. In the initial screening phase, titles and abstracts of the retrieved articles were independently assessed by two reviewers for potential relevance based on the predefined inclusion and exclusion criteria. This preliminary assessment aimed to eliminate any clearly irrelevant studies, such as those not pertaining to electronic cigarettes and periodontal outcomes. Studies that passed the initial screening phase were then subjected to a full-text review. During this stage, two reviewers independently examined the full texts to confirm each study’s eligibility based on more detailed criteria. This included a closer examination of the study’s methodology, the specificity of the periodontal outcomes measured, and the population studied in relation to e-cigarette usage. Any discrepancies between reviewers regarding the inclusion of a study were resolved through discussion or third-party adjudication. Data extraction Data from the included studies were meticulously extracted by two independent reviewers using a standardized data extraction form. The information collected encompassed several key areas: study characteristics, participant demographics, details of e-cigarette use, and the outcomes assessed. Specifically, the study characteristics included the author, year of publication, study design, and sample size. Participant demographics covered age, sex, and smoking history. Detailed information regarding e-cigarette use, such as the duration, frequency, and type of device used, was also recorded. The outcomes assessed included bleeding on probing (BOP), plaque index, clinical attachment loss, mesial and distal bone loss, and measures of association for periodontitis. This systematic approach ensured a comprehensive and consistent collection of relevant data across all included studies. Quality assessment The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS) for observational studies. Studies were graded on selection, comparability, and outcome assessment, with higher scores indicating better quality. Statistical analysis A meta-analysis was conducted to aggregate the continuous outcomes from each study, utilizing means and standard deviations (SD). Random-effect models were applied to this meta-analysis to account for variability among the studies. Subsequently, forest plots were created to visually represent the results. To evaluate the heterogeneity of the included studies, the I 2 statistic was employed. This statistic quantifies the proportion of total variation across studies due to heterogeneity rather than chance, and it ranges from 0 to 100%, with higher percentages indicating greater heterogeneity. Additionally, the tau-squared value was calculated using maximum likelihood estimation to provide a more precise measurement of between-study variance . To check for publication bias, funnel plots, and the Egger test were used. A p-value of less than 0.05 was considered to indicate statistical significance. All statistical analyses were carried out using the R software, version 4.3 . 

A comprehensive literature search was conducted across several electronic databases including PubMed, EMBASE, and Web of Science. The search was performed from inception of each database up to up to June 15, 2024. No filters were imposed on the basis of type of article or language in the search. The keywords used in the search were combinations of: “electronic cigarettes,” “periodontitis,” and other keywords related to periodontal outcomes. Boolean operators (AND, OR) were used to combine the search terms. A detailed search strategy is presented in Table S2. 

The systematic review incorporated studies that specifically examined the effects of e-cigarette use on various periodontal outcomes. Eligible studies were required to assess outcomes such as risk for periodontitis, bleeding on probing, probing depth, plaque index, medial bone loss, distal bone loss, and clinical attachment loss. Comparison group involved E-cigarette never users or non-users as reported by studies. Due to inconsistencies in the classification of e-cigarette users across the included studies, we used ‘never users’ and ‘non-users’ interchangeably as the comparison group, based on the terminology provided in each study. This represents a minor deviation from our original protocol. This review considered observational studies, including cohort, case-control, and cross-sectional designs, as well as clinical trials, to capture a broad range of evidence. On the other hand, certain types of publications were excluded from the review to maintain a focus on relevant and high-quality data. Excluded were studies that did not offer specific data on periodontal outcomes, ensuring that the review remained focused on the primary interest area. Additionally, case reports, editorials, and review articles were omitted, as these typically do not present original research data. Animal studies were also excluded, aligning the review strictly with human research. Studies available in English language only were included. 

Following the initial search, all identified records were collated and uploaded into a the Nested-Knowledge platform to manage and track the screening process. The screening was conducted in two stages to efficiently filter the relevant studies. In the initial screening phase, titles and abstracts of the retrieved articles were independently assessed by two reviewers for potential relevance based on the predefined inclusion and exclusion criteria. This preliminary assessment aimed to eliminate any clearly irrelevant studies, such as those not pertaining to electronic cigarettes and periodontal outcomes. Studies that passed the initial screening phase were then subjected to a full-text review. During this stage, two reviewers independently examined the full texts to confirm each study’s eligibility based on more detailed criteria. This included a closer examination of the study’s methodology, the specificity of the periodontal outcomes measured, and the population studied in relation to e-cigarette usage. Any discrepancies between reviewers regarding the inclusion of a study were resolved through discussion or third-party adjudication. 

Data from the included studies were meticulously extracted by two independent reviewers using a standardized data extraction form. The information collected encompassed several key areas: study characteristics, participant demographics, details of e-cigarette use, and the outcomes assessed. Specifically, the study characteristics included the author, year of publication, study design, and sample size. Participant demographics covered age, sex, and smoking history. Detailed information regarding e-cigarette use, such as the duration, frequency, and type of device used, was also recorded. The outcomes assessed included bleeding on probing (BOP), plaque index, clinical attachment loss, mesial and distal bone loss, and measures of association for periodontitis. This systematic approach ensured a comprehensive and consistent collection of relevant data across all included studies. 

The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS) for observational studies. Studies were graded on selection, comparability, and outcome assessment, with higher scores indicating better quality. 

A meta-analysis was conducted to aggregate the continuous outcomes from each study, utilizing means and standard deviations (SD). Random-effect models were applied to this meta-analysis to account for variability among the studies. Subsequently, forest plots were created to visually represent the results. To evaluate the heterogeneity of the included studies, the I 2 statistic was employed. This statistic quantifies the proportion of total variation across studies due to heterogeneity rather than chance, and it ranges from 0 to 100%, with higher percentages indicating greater heterogeneity. Additionally, the tau-squared value was calculated using maximum likelihood estimation to provide a more precise measurement of between-study variance . To check for publication bias, funnel plots, and the Egger test were used. A p-value of less than 0.05 was considered to indicate statistical significance. All statistical analyses were carried out using the R software, version 4.3 . 

Literature search The search yielded a total of 398 records. These records were sourced from PubMed (135 records), Embase (160 records), and Web of Science (103 records). Before screening, duplicates were identified and removed, resulting in 203 records being excluded. This left 195 records to be screened based on titles and abstracts. From these, 162 records were excluded for not meeting the study inclusion criteria, which left 33 reports that were sought for detailed assessment. Full-text articles for all 33 records were retrieved and assessed for eligibility. Out of these, 17 articles were further excluded for various reasons: 10 did not report the outcomes of interest, 5 did not involve the exposure of interest, and 6 studied populations outside the scope of this review. Ultimately, 12 studies  were found to be eligible and were included in the qualitative and quantitative analysis (Fig. ). Characteristics of included studies The key characteristics of the included studies are summarized in Table . The studies were primarily conducted in Saudi Arabia, with additional data from the USA, Kuwait, Malaysia, Pakistan, South Korea, and Turkey. These investigations employed various designs, including cross-sectional, case-control, and one longitudinal study, with sample sizes ranging from 45 to 13,551 participants. The majority of studies focused on populations of electronic cigarette users, cigarette smokers, waterpipe smokers, and non-smokers, comparing these groups to assess the effects on periodontal health. Detailed demographic data such as mean age or gender distribution were often not provided, and many studies did not report specific odds ratios or confidence intervals for periodontitis. The quality assessment of these studies is detailed in Table S3. Notably, Arshi et al.  from Pakistan reported an OR of 5.42 (95% CI: 2.52 to 11.69) for periodontitis associated with e-cigarette use. Similarly, Jeong et al.  from South Korea also reported an OR of 2.34 (95% CI: 1.52 to 3.59) for periodontitis. Bleeding on probing The meta-analysis from 5 studies summarized in the forest plot compared the BOP between e-cigarette users and non-users across various studies (Fig. ). The studies included were diverse, encompassing various countries and sample sizes. The analysis revealed a significant difference in BOP scores between the groups, with e-cigarette users generally having lower scores. The overall pooled mean difference was − 14.233 (95% CI: -20.424 to -8.043), indicating a statistically significant lower BOP score among e-cigarette users compared to non-users. The studies exhibited high heterogeneity (I² = 99%), suggesting considerable variation in the results across the studies. Clinical attachment loss The meta-analysis, comprising nine studies compared clinical attachment loss between e-cigarette users and non-users across a diverse range of countries (Fig. ). The total pooled sample sizes were 233 for e-cigarette users and 230 for non-users. Sample sizes within individual studies ranged from 15 to 51 participants. The pooled mean difference was 0.353 (95% CI: -0.233 to 0.939), indicating a non-statistically significant increase in clinical attachment loss among e-cigarette users compared to non-users ( p = 0.2380). The analysis revealed high heterogeneity (I² = 100%). Plaque index The meta-analysis from ten studies, detailed in a forest plot, compared the plaque index between e-cigarette users and non-users across various international settings, with a total pooled sample size of 227 e-cigarette users and 218 non-users (Fig. ). The analysis revealed a significant mean difference in the plaque index, with e-cigarette users having an average increase of 6.20 (95% CI: -0.631 to 13.031) compared to non-users, suggesting no significant level of plaque accumulation among this group ( p = 0.0007). The studies exhibited extreme heterogeneity (I² = 100%). Probing depth The meta-analysis from eleven studies compared probing depths between e-cigarette users and non-users, incorporating data from diverse geographical regions with a total pooled sample size of 202 e-cigarette users and 200 non-users (Fig. ). The analysis showed an overall pooled mean difference of 0.340 (95% CI: -0.386 to 1.065), suggesting a non-statistically significant difference in probing depths between the two groups ( p = 0.358). Substantial variability across studies as indicated by the 100% heterogeneity (I² = 100%). Distal marginal bone loss The meta-analysis comprising eight studies focused on comparing distal marginal bone loss between e-cigarette users and non-users (Fig. ). This analysis, illustrated in a forest plot, incorporated studies with a total pooled sample size of 182 e-cigarette users and 173 non-users. The overall mean difference observed was 0.531 (95% CI: -0.565 to 1.627), indicating a non-statistically significant trend toward greater bone loss in e-cigarette users compared to non-users, though the results varied across studies ( p = 0.342). The heterogeneity was high (I² = 100%). Mesial marginal bone loss The meta-analysis, including eight studies, assessed mesial marginal bone loss comparing e-cigarette users with non-users (Fig. ). This analysis summarized findings from a total pooled sample size of 182 e-cigarette users and 173 non-users. The overall mean difference for mesial marginal bone loss was 0.516 (95% CI: -0.533 to 1.564), which indicates a non-statistically significant effect ( p = 0.3353). Notable heterogeneity was observed across the studies (I² = 100%). Publication bias We assessed publication bias using funnel plots and the Egger test. No publication bias was detected from the funnel plots or the Egger test for any of the outcomes (Figs. S1 to S6). 

The search yielded a total of 398 records. These records were sourced from PubMed (135 records), Embase (160 records), and Web of Science (103 records). Before screening, duplicates were identified and removed, resulting in 203 records being excluded. This left 195 records to be screened based on titles and abstracts. From these, 162 records were excluded for not meeting the study inclusion criteria, which left 33 reports that were sought for detailed assessment. Full-text articles for all 33 records were retrieved and assessed for eligibility. Out of these, 17 articles were further excluded for various reasons: 10 did not report the outcomes of interest, 5 did not involve the exposure of interest, and 6 studied populations outside the scope of this review. Ultimately, 12 studies  were found to be eligible and were included in the qualitative and quantitative analysis (Fig. ). 

The key characteristics of the included studies are summarized in Table . The studies were primarily conducted in Saudi Arabia, with additional data from the USA, Kuwait, Malaysia, Pakistan, South Korea, and Turkey. These investigations employed various designs, including cross-sectional, case-control, and one longitudinal study, with sample sizes ranging from 45 to 13,551 participants. The majority of studies focused on populations of electronic cigarette users, cigarette smokers, waterpipe smokers, and non-smokers, comparing these groups to assess the effects on periodontal health. Detailed demographic data such as mean age or gender distribution were often not provided, and many studies did not report specific odds ratios or confidence intervals for periodontitis. The quality assessment of these studies is detailed in Table S3. Notably, Arshi et al.  from Pakistan reported an OR of 5.42 (95% CI: 2.52 to 11.69) for periodontitis associated with e-cigarette use. Similarly, Jeong et al.  from South Korea also reported an OR of 2.34 (95% CI: 1.52 to 3.59) for periodontitis. 

The meta-analysis from 5 studies summarized in the forest plot compared the BOP between e-cigarette users and non-users across various studies (Fig. ). The studies included were diverse, encompassing various countries and sample sizes. The analysis revealed a significant difference in BOP scores between the groups, with e-cigarette users generally having lower scores. The overall pooled mean difference was − 14.233 (95% CI: -20.424 to -8.043), indicating a statistically significant lower BOP score among e-cigarette users compared to non-users. The studies exhibited high heterogeneity (I² = 99%), suggesting considerable variation in the results across the studies. 

The meta-analysis, comprising nine studies compared clinical attachment loss between e-cigarette users and non-users across a diverse range of countries (Fig. ). The total pooled sample sizes were 233 for e-cigarette users and 230 for non-users. Sample sizes within individual studies ranged from 15 to 51 participants. The pooled mean difference was 0.353 (95% CI: -0.233 to 0.939), indicating a non-statistically significant increase in clinical attachment loss among e-cigarette users compared to non-users ( p = 0.2380). The analysis revealed high heterogeneity (I² = 100%). 

The meta-analysis from ten studies, detailed in a forest plot, compared the plaque index between e-cigarette users and non-users across various international settings, with a total pooled sample size of 227 e-cigarette users and 218 non-users (Fig. ). The analysis revealed a significant mean difference in the plaque index, with e-cigarette users having an average increase of 6.20 (95% CI: -0.631 to 13.031) compared to non-users, suggesting no significant level of plaque accumulation among this group ( p = 0.0007). The studies exhibited extreme heterogeneity (I² = 100%). 

The meta-analysis from eleven studies compared probing depths between e-cigarette users and non-users, incorporating data from diverse geographical regions with a total pooled sample size of 202 e-cigarette users and 200 non-users (Fig. ). The analysis showed an overall pooled mean difference of 0.340 (95% CI: -0.386 to 1.065), suggesting a non-statistically significant difference in probing depths between the two groups ( p = 0.358). Substantial variability across studies as indicated by the 100% heterogeneity (I² = 100%). 

The meta-analysis comprising eight studies focused on comparing distal marginal bone loss between e-cigarette users and non-users (Fig. ). This analysis, illustrated in a forest plot, incorporated studies with a total pooled sample size of 182 e-cigarette users and 173 non-users. The overall mean difference observed was 0.531 (95% CI: -0.565 to 1.627), indicating a non-statistically significant trend toward greater bone loss in e-cigarette users compared to non-users, though the results varied across studies ( p = 0.342). The heterogeneity was high (I² = 100%). 

The meta-analysis, including eight studies, assessed mesial marginal bone loss comparing e-cigarette users with non-users (Fig. ). This analysis summarized findings from a total pooled sample size of 182 e-cigarette users and 173 non-users. The overall mean difference for mesial marginal bone loss was 0.516 (95% CI: -0.533 to 1.564), which indicates a non-statistically significant effect ( p = 0.3353). Notable heterogeneity was observed across the studies (I² = 100%). 

We assessed publication bias using funnel plots and the Egger test. No publication bias was detected from the funnel plots or the Egger test for any of the outcomes (Figs. S1 to S6). 

The impact of e-cigarettes on periodontal health is a topic of significant clinical and public health interest, especially given the increasing prevalence of e-cigarette use globally. This systematic review and meta-analysis aimed to comprehensively assess the existing evidence regarding the effects of e-cigarettes on periodontitis and related periodontal outcomes. The primary periodontal outcomes assessed in this review were BOP, plaque index, probing depth, and marginal bone loss (both mesial and distal). The pooled analyses revealed varied results. A lower mean BOP was noted in E-cigarette group compared to non-users. This finding was counterintuitive, given the inflammatory potential of nicotine, a common component of both traditional and electronic cigarettes. The results for probing depth, plaque index and marginal bone loss did not show significant differences between e-cigarette users and non-users, indicating that the impact of e-cigarettes on these parameters might be less pronounced or that longer-term studies are needed to detect changes. The high heterogeneity observed across the studies for most outcomes shows the variability in study designs, populations, and methodological approaches. This variability may also reflect differences in the types and components of e-cigarettes used and, in the duration, and intensity of use. A previous meta-analysis examined the effects of electronic cigarettes on periodontal health compared to conventional cigarette smoke and a non-smoking population. Their analysis revealed that cigarette smokers had significantly higher plaque index, probing depth, attachment loss, marginal bone loss, and increased concentrations of pro-inflammatory mediators compared to e-cigarette users and non-smokers. However, they did not provide sufficient analysis for e-cigarettes versus non-smokers or never-smokers. Our study is the first meta-analysis to measure these effects . It is crucial to consider the potential confounding factors that may influence the observed periodontal outcomes. Participants may have exhibited multiple lifestyle habits that could affect periodontal health, such as the use of traditional tobacco products or alcohol consumption alongside e-cigarette use. These co-existing habits can potentially exacerbate periodontal conditions and obscure the specific effects attributable solely to e-cigarettes. Therefore, the studies indicating more severe periodontal effects in e-cigarette users often involve individuals with these additional risk factors. The findings from this review have important implications for clinical practice and public health policy. Dentists and other healthcare providers should be aware of the potential periodontal risks associated with e-cigarette use and should include an assessment of vaping in their routine medical history taking. From a public health perspective, these results support the need for ongoing monitoring of e-cigarette use and its health effects, as well as the potential regulation of e-cigarette products to minimize their harm. Further research is necessary to better understand the long-term effects of e-cigarettes on periodontal health. Future studies should aim to standardize outcome measures and adjust for confounding factors such as age, oral hygiene practices, and socioeconomic status. Additionally, experimental studies could provide insights into the pathophysiological mechanisms by which e-cigarette components, such as nicotine and flavoring agents, affect periodontal tissues. Our study has some limitations. The cross-sectional nature of many studies included in the analysis limits the ability to establish causality between e-cigarette use and periodontal outcomes. Longitudinal studies would provide stronger evidence of causal relationships. Additionally, the variability in how e-cigarette use is reported and classified across studies poses challenges for drawing generalizable conclusions. We only included articles in English. The comparison groups might have differed across studies in their definitions, with some studies comparing e-cigarette users to never-users, while others compare them to non-users; this variation may contribute to heterogeneity. 

Current evidence does not find a significant association of e-cigarette use with negative periodontal effects, although the research is limited. More longitudinal observational studies are needed to study the long-term impacts of e-cigarette use on periodontal health and to provide a clearer understanding of any potential risks involved. 

Supplementary Material 1. 

