Association between Oral Hygiene and Metabolic Syndrome: A Systematic Review and Meta-Analysis

Emerging evidence has linked poor oral hygiene to metabolic syndrome (MetS), but previously, no summary of evidence has been conducted on the topic. This systematic review and meta-analysis aims to evaluate the associations of oral hygiene status and care with MetS. A systematic search of the PubMed and Web of Science databases from inception to 17 March 2021, and examination of reference lists was conducted to identify eligible observational studies. A random-effects model was applied to pool the effects of oral hygiene status and care on MetS. Thirteen studies met the inclusion criteria and had sufficient methodological quality. Good oral hygiene status (OR = 0.30 (0.13–0.66); I2 = 91%), frequent tooth brushing (OR = 0.68 (0.58–0.80); I2 = 89%), and frequent interdental cleaning (OR = 0.89 (0.81–0.99); I2 = 27%) were associated with a lower risk of MetS. Only one study examined the association between dental visits and MetS (OR = 1.10 (0.77–1.55)). Our findings suggested that there might be inverse associations of oral hygiene status, tooth-brushing frequency, and interdental cleaning with MetS. However, substantial heterogeneity for tooth-brushing frequency and inconsistent results for oral hygiene status in subgroup analyses were observed. There was insufficient evidence for the association between dental visits and MetS. Further longitudinal studies are needed to investigate these associations.


Introduction
Metabolic syndrome (MetS), a clustering of abdominal obesity, hyperglycemia, hypertension, and dyslipidemia, represents a growing public health concern globally [1].Although the prevalence of MetS differs depending on diagnostic criteria, age group, and ethnicity [1,2], it is estimated to affect around 25% of the world population [2,3].MetS raises the risk of type 2 diabetes mellitus (T2DM) and cardiovascular diseases [1] and is associated with a 20% increase in healthcare costs [4].
Several risk factors for MetS have been identified.Besides socioeconomic status (SES) [5], smoking [6], diet [7], and physical activity [8], oral diseases, such as periodontal diseases and dental caries, are associated with .The link between oral and systemic diseases is suggested due to common risk factors, subgingival biofilm harboring Gram-negative bacteria, and periodontium serving as a cytokine reservoir [12].
Poor oral hygiene is the primary cause of common oral diseases.Accumulation of dental plaque allows bacterial growth that may lead to inflamed periodontal tissues and eventually create bacteremia and systemic inflammation [13,14].Invading bacteria from severe caries or endodontic infections is also thought to provoke similar mechanisms [10,15,16].Chronic low-grade inflammation underlies the development of metabolic disorders [17,18], and a study found that systemic exposure to periodontal bacteria was associated with MetS [13].
Tooth brushing and interdental cleaning, which are the main forms of oral self-care, together with regular professional care, are important measures for plaque control or removal and maintaining optimal oral health [19][20][21].Poor oral hygiene care is associated with low-grade inflammation [22], suggesting its potential link to MetS [23].The association of poor oral hygiene care with a higher risk of the components of MetS, such as obesity [24], diabetes [25,26], hypertension [26,27], and dyslipidemia [26,28], as well as with cardiovascular disease [14,22], has been demonstrated.
Although several epidemiological studies have reported the association of oral hygiene status [29] and care [23,30] with MetS, some studies found no such association [31,32].To date, there has not been a systematic review conducted on the topic.A summary of evidence can provide a better understanding of the potential relationship and help healthcare practitioners deliver more targeted care.It can provide more substance for the formulation of public health programs and policies, especially strategies for the prevention and management of MetS.
The aim of our study was to systematically review the association of oral hygiene status and care with MetS and to quantify the strength of associations.

Materials and Methods
The systematic review and meta-analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [33].The protocol was registered on the PROSPERO database (No.CRD42021243292) [34].The research question was: Is better oral hygiene status or care associated with a lower risk of MetS?

Eligibility Criteria
The inclusion criteria were as follows: (1) The design of the study was cross-sectional, case-control, or cohort; (2) the exposure was oral hygiene status (e.g., oral hygiene index (OHI), plaque index (PI), plaque score (PSc)) or care (i.e., tooth brushing, interdental cleaning, and dental visit); (3) the outcome was MetS, clearly defined using diagnostic criteria for the condition (e.g., National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), International Diabetes Federation (IDF), Joint Interim Statement (JIS)); (4) the study assessed the association between exposures and outcome in multiple analysis.There was no limitation on the characteristics of the study population.Animal studies, clinical trials, reviews, editorial letters, commentaries, case series, and case reports were excluded.

Search Strategy
A systematic search was performed on the PubMed and Web of Science databases, with the following keywords: oral hygiene, dental deposit, OHI, PI, PSc, tooth brushing, interdental cleaning, dental visit, and MetS.While no date restrictions were imposed, the language was limited to English.The last search was on 17 March 2021.Details of the search strategy can be seen in Supplementary Table S1.Examination of reference lists of eligible studies and relevant systematic reviews were also conducted to identify further relevant studies.

Study Selection and Data Extraction
Two authors independently screened all titles and abstracts to evaluate eligibility.Relevant studies were then examined for full-text review.Any ambiguities or disagreements were resolved by consensus.JabRef 5.2 was used during the review process.
Data from included studies were extracted independently by two authors using a data extraction form.The following information was collected: first author, publication year, study country, study design, sample size, age, gender, type of oral hygiene assessment, diagnostic criteria used for MetS, number of MetS cases, adjusted odds ratio (OR) or risk ratio (RR) with 95% confidence interval (CI), and adjustment factors.Discrepancies in data extraction were resolved by consensus.

Quality Assessment
Two authors independently examined the quality of included studies using the Newcastle-Ottawa Scale for cross-sectional, case-control, and cohort studies, as applicable.The three main domains examined were the selection of participants, comparability of study groups, and assessment of exposure/outcome of interest.The total scores for casecontrol and cohort studies were 9 points, while cross-sectional studies were 8 points [35,36].The included studies were then categorized into high (≥7 points), moderate (4-6 points), or low (0-3 points) quality.Any disagreements were resolved by consensus.

Statistical Analyses
Meta-analysis was conducted separately for different types of exposure (i.e., oral hygiene status, tooth brushing, and interdental cleaning).The OR was used as the common measure for the association between oral hygiene and MetS.The reported RR was considered approximately as OR [37].The data utilized in the meta-analysis were the estimates and the corresponding 95% CI from the most adjusted model in the studies.
The categorization of exposure varied between studies.Poor oral hygiene status or care was used as the reference group, equivalent to the highest value of OHI, PI, and PSc or the lowest frequency category of tooth brushing, interdental cleaning, and dental visits in each study.If a study classified the exposure into more than two categories, a single effect estimate was produced by combining the results of the categories using a fixed-effects (FE) model [38].An overall pooled OR for the main analysis was calculated using a random-effects (RE) model (DerSimonian and Laird).
Heterogeneity was assessed using the I 2 statistic, with the value of ≥50% representing substantial heterogeneity [37,39].Potential sources of heterogeneity were assessed using prespecified subgroup analyses by study design and country.Examination of publication bias using funnel plot and Egger's test was only recommended if there were an adequate number of studies (>10) [40,41].
Meta-analysis was conducted using the generic inverse variance method in Review Manager (RevMan) 5.4 software (The Cochrane Collaboration, 2020) [42].

Literature Search
Figure 1 shows the process and the results of study selection.A total of 595 records were identified, of which 144 were duplicates; 380 irrelevant studies were eliminated.Of the 71 studies selected for full-text review, 13 met the eligibility criteria and were included in the review and meta-analysis.

Characteristics of Studies
Table 1 shows the main characteristics of the included studies.They consisted of seven cross-sectional, three case-control, and three cohort studies.A study by Shearer et al. [32] examined data from a cohort study.However, because our exposure of interest (modified OHI-S) was measured simultaneously with the outcome (MetS) at age 38, we chose to consider it as cross-sectional and reported the results of their cross-sectional model.
Eleven studies were from Asian countries, and one study each was from Finland and New Zealand.All were conducted among adult populations.Publication years ranged from 2009 to 2020, and the mean sample size was 4251.
Six studies reported oral hygiene status, six studies reported tooth-brushing frequency, two studies reported interdental cleaning, and one study reported dental visits as study factors.In the meta-analysis, a study by Tsutsumi et al. [43] was treated as two separate studies, as it reported the results independently for males and females instead of total samples.A similar approach was applied to a study by Kim et al. [44], as it provided separate data on interdental brushing and flossing.
Health examination was performed in all included studies to ascertain MetS conditions.Four studies used the NCEP ATP III criteria or its adapted version, five studies used JIS criteria, two used IDF criteria, and two used other criteria to define MetS.The most common confounders adjusted in the studies were age, gender, SES, smoking status, alcohol consumption, physical activity, and periodontal parameters.All studies reported a measure of associations as ORs, except for one study [31].

Quality Aspects of Studies
All the included studies were of moderate to high quality.One cross-sectional study, two case-control studies, and three cohort studies were of high quality.Six cross-sectional studies and one case-control study were of moderate quality.Details of the quality assessment of included studies can be seen in Supplementary Table S2.

Association between Oral Hygiene Status, Care, and MetS
Figure 2 shows the results of the meta-analysis of associations of oral hygiene status, tooth-brushing frequency, and interdental cleaning with MetS.Good oral hygiene (OR = 0.30; 95% CI = 0.13-0.66),frequent tooth brushing (OR = 0.68; 95% CI = 0.58-0.80),and frequent interdental cleaning (OR = 0.89; 95% CI = 0.81-0.99)were associated with a lower risk of MetS.While heterogeneity was minimal for interdental cleaning (I 2 = 27%), there was substantial heterogeneity for oral hygiene status (I 2 = 91%) and tooth-brushing frequency (I 2 = 89%).The association between dental visits and MetS was evaluated only in a study by Tanaka et al.It was found that dental visits were not significantly associated with MetS (OR = 1.10; 95% CI = 0.77-1.55)[23].

Subgroup Analyses
Table 2 displays the results of subgroup analysis by study design for the association between oral hygiene status and MetS.The inverse association between oral hygiene status and MetS was only observed in the subgroup of case-control studies.Subgroup analysis by study design reduced heterogeneity to less than 50%.Table 3 shows the results of subgroup analyses for the association between toothbrushing frequency and MetS.Frequent tooth brushing was consistently associated with a lower risk of MetS in all subgroup analyses.However, high heterogeneity was still observed among studies with a cross-sectional design.While subgroup analysis by country reduced heterogeneity, it remained above 50%.

Discussion
Our systematic review and meta-analysis investigated the association of oral hygiene status and care with MetS.Better oral hygiene status, frequent tooth brushing, and frequent interdental cleaning were associated with a lower risk of MetS.However, substantial heterogeneity for tooth-brushing frequency and inconsistent results for oral hygiene status in subgroup analyses were noted.Our review identified only one study examining the association between dental visits and MetS, and found no association [23].
While our main analysis revealed an inverse association between better oral hygiene status and MetS, the finding was inconsistent in subgroup analysis by study design.Of all studies included in the meta-analysis for oral hygiene status, only studies by Shearer et al. [32] and Pussinen et al. [31], conducted in New Zealand and Finland, respectively, did not find an association.These different findings might be due to the age of the study samples.Both studies had relatively younger samples than the other studies, which had a sample mean age of more than 50 years.The stronger influence of periodontal inflammations on cardiometabolic health may only be observed in later life [32].Moreover, Pussinen et al. [31] reported both the adjusted RRs for MetS and β values for the number of MetS components.While the adjusted RR for the association between the presence of plaque and MetS was not significant, the β value for the association between the number of teeth with plaque and the number of MetS components was significant [31].
Our overall findings are in line with other systematic reviews and meta-analyses that demonstrated an association between oral health or hygiene and metabolic conditions [9,37].Poor oral hygiene not only leads to dental infections, such as periodontitis, but it may also affect systemic health [55].Periodontal bacteria in plaque, their products, and resulting local inflammatory response may enter the bloodstream, directly contributing to systemic inflammation [56].Chronic exposure to proinflammatory cytokines, such as TNF-α and IL-1β, may alter lipid metabolism, causing hyperlipidemia [57].TNF-α may induce insulin resistance by directly affecting target organs (e.g., liver, muscle, and adipocytes) and by indirectly promoting the production of free fatty acids from adipocytes [58].Elevated levels of proinflammatory cytokines may also contribute to pancreatic β-cells dysfunction, leading to the development of T2DM [57,[59][60][61].Moreover, recent evidence showed that Porphyromonas gingivalis might induce metabolic impairment by altering the gut microbiome [62].
Our study showed inverse relationships of tooth-brushing frequency and interdental cleaning with MetS.Despite substantial heterogeneity, the findings of all subgroup analyses of tooth-brushing frequency were consistent.Tooth brushing is the most crucial self-care measure to control plaque and is a protective factor against periodontal diseases [63,64].While a suggestion for proper frequency of tooth brushing could not be given, most of the included studies used a cut-off point of twice or more daily.Another review showed similar findings and indicated that brushing less than twice daily might not be beneficial for the prevention of DM [37].In addition to tooth brushing, interdental cleaning is recommended for maintaining oral health.The daily use of interdental brushes was found to decrease periodontal bacteria, promote symbiotic microbiota, and reduce interdental inflammation [65].It was suggested that poor oral hygiene could exaggerate MetS by increasing local and systemic inflammation [66].
An alternative explanation for the association between oral hygiene care and MetS might be that it is due to shared risk factors [14] or biased health consciousness.People with a healthier lifestyle might tend to adopt better oral hygiene care [67].The fact that oral hygiene care may merely be an indicator of general health awareness or behaviors underscores the complexity of oral epidemiology [68].However, most of the included studies in our review accounted for important confounders, such as age, gender, SES, smoking status, alcohol consumption, and physical activity, minimizing the bias.
The association between dental visits and MetS was not demonstrated in the study by Tanaka et al. [23].This finding was similar to another study demonstrating no associations between dental visits, professional dental cleaning, and diabetes.It was argued that other confounders had more important roles in the development of diabetes than professional dental cleaning [25].However, an earlier review has demonstrated the benefit of scaling and root planing on metabolic control and systemic inflammation reduction in patients with T2DM [69].
This systematic review and meta-analysis was the first to explore the association of oral hygiene status and care with MetS.The topic is seen as recent in the scientific literature, with the earliest identified studies published in 2009.It is also related to an emerging interest in the interrelationships between oral pathogens, oral microbiome dysbiosis, and systemic conditions [70].Exploring this topic is relevant considering the importance of formulating policies with common risk factors approach to address both oral and general health [71].Another strength of our review was the quality of the studies, which was moderate to high.
Our review might be limited by the methodological weakness of the included studies with a cross-sectional design.The number of cohort studies was also limited.Moreover, the restriction of studies to those published in English and the exclusion of a grey literature search might introduce bias.The risk of publication bias could not be ruled out and was not assessed in our study due to an inadequate number of studies and high heterogeneity.
Besides study design and country, the potential source of heterogeneity might be from the variability in measurement methods of oral hygiene status (e.g., the use of different indices) and the reporting of tooth-brushing frequency and interdental cleaning between studies.Moreover, the criteria used to define MetS varied.
Information on tooth-brushing frequency and interdental cleaning was self-reported, which might be prone to bias.However, it might only be the type of nondifferential misclassification, leading to the underestimation of true effect estimates.Regular brushing does not necessarily reflect effective brushing, as the studies did not adjust for the duration and method of tooth brushing and the type of dentifrice used.
Finally, most of the included studies in our review were conducted among an Asian population, which may influence the generalizability of the findings worldwide.Further research conducted among other populations is warranted to provide more evidence.Using a uniform protocol for reporting oral hygiene (e.g., tooth-brushing frequency) may also facilitate better comparison.

Conclusions
Our study found that there might be inverse associations of oral hygiene status, tooth-brushing frequency, and interdental cleaning with MetS.However, substantial heterogeneity for tooth-brushing frequency and inconsistent results for oral hygiene status in subgroup analyses were observed.There was insufficient evidence on the association between dental visits and MetS.Further well-conducted studies, preferably of longitudinal design, are needed to confirm the associations of oral hygiene status and care with MetS and to explore their underlying mechanisms.Research on this topic will provide a valuable contribution to our current understanding of the interrelationship between oral health and MetS.

Figure 1 .
Figure 1.PRISMA flow diagram of the literature search and study selection[33].MetS, metabolic syndrome.

Figure 2 .
Figure 2. Meta-analysis of the associations of (a) oral hygiene status, (b) tooth-brushing frequency, and (c) interdental cleaning with metabolic syndrome.

Table 1 .
Main characteristics of the 13 included studies.

Table 2 .
Subgroup analysis by study design for the association between oral hygiene status and MetS.

Table 3 .
Subgroup analyses for the association between tooth-brushing frequency and MetS.