Inflammation represents the response of an organism to a noxious stimulus, which can be elicited by injury or destruction of tissues, which serves to destroy, dilute, or wall off both the injurious agent and the injured tissue. It is mediated by either humoral or cellular response of host. Chronic periodontitis is one such infectious inflammatory disease that results from an imbalance between commensal microbiome and the host immune response. The hyperinflammatory uncontrolled immune lesion promotes local tissue damage and impedes effective bacterial clearance. Failure to resolve the inflammation coupled with resultant microbiome changes is hypothesized to drive the development of periodontitis. Gingivitis is a reversible inflammatory reaction of marginal gingival to plaque accumulation, whereas periodontitis is a destructive, nonreversible condition, resulting in loss of tooth connective tissue attachment to bone which ultimately leads to loss of the involved teeth.
A characteristic inflammatory site consists of tissue infiltration by PMNs and monocytes, which leads to the generation of free radicals and reactive oxygen species (ROS) such as peroxide and hypochlorous acid, which are all well equipped to damage either the cell membranes or associated biomolecules. Pathogens can induce ROS overproduction and thus may cause collagen and periodontal cell breakdown. Oxidative stress arises within tissues when there is an imbalance between ROS generation and antioxidant defense.
Antioxidants are those substances, which, when present at low concentrations compared to those of oxidizable substrate, will significantly delay or inhibit oxidation of that substrate. Coenzyme Q10 (CoQ10) is an antioxidant that exists in an oxidized form (ubiquinone or CoQ) and a reduced form (ubiquinol or CoQH2). It inhibits lipid peroxidation by preventing the production of lipid peroxyl radicals. Furthermore, the reduced form of CoQ10 effectively regenerates Vitamin E from a-tocopherol radicals.
Coenzyme Q10 was discovered in beef heart mitochondria at the University of Wisconsin. It is also known as ubiquinone because of its ubiquitous presence in nature and its quinone structure, which means that it is similar to Vitamin K. It is also called as “Coenzyme” because of its unique ability to participate in chemical reactions, but remains at steady-state levels in the cell. Coenzyme Q10 exists naturally in the mitochondria of all cells in the human body. Physiologically, CoQ10 plays four major roles: (1) it has an essential role in ATP production, (2) it plays a role in extramitochondrial redox activity in the cell membrane, (3) it functions as an antioxidant, inhibiting lipid peroxidation and scavenging free radicals, and (4) it plays an important role in membrane stabilization and fluidity. A deficiency of CoQ has been found in the gingiva of patients with periodontal disease (Littarru et al., 1971, and Nakamura et al., 1973). The results have shown that oral administration of CoQ increases the concentration of CoQ10 in the diseased gingiva and effectively suppresses advanced periodontal inflammation. A study conducted by Pal et al., 2012, evaluated the efficacy of coenzyme Q gel as an adjunct to scaling and root planing (SRP) in the management of gingivitis and slight periodontitis patients and the results showed decrease in the clinical parameters in the test groups treated with coenzyme Q gel as compared to groups treated with SRP alone. Furthermore, when ROS are scavenged by antioxidants like CoQ10, there can be reduction in periodontal collagen degradation. There can be two methods to deliver it, i.e., topical application and intrasulcular application. The topical method is more convenient in a normal dental setting, whereas an intrasulcular approach proves to be a little bit technique sensitive method. Thus, in the present article, we compiled the results of application of CoQ for the treatment of periodontal diseases.
MATERIALS AND METHODS
The review protocol was registered on an international database of prospective registration ID (CRD42021244659) systemic review to avoid any unintended repetition of review on this subject. Our research question was “Is topical and intrasulcular application of coenzyme Q10 effective in nonsurgical treatment of periodontal disease?” We strictly followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
The following P-I-C-O model was used
Participants or study population were the subjects who were suffering from periodontal disease. Both gingivitis and periodontitis were included.
Intervention: All the subjects were treated with topical and/or intrasulcular application of Coenzyme Q.
Comparison: Efficacy of coenzyme Q was compared by intrasulcular and/or topical application with and without scaling and root planing.
Outcome: Clinical parameters such as probing pocket depth, gingival bleeding, and clinical attachment levels (CALs) were evaluated at 1 month and 3 months.
Search and selection criteria
PubMed, Embase, Web of Science, and Cochrane Library electronic databases and Google Scholar were searched. Along with the electronic search, a manual search was also performed from the most relevant journals in periodontology. Electronic search was made using keywords: (“Co-enzyme Q10”) AND (Chronic Periodontitis OR Periodontitis OR Gingivitis) AND (Scaling and root planning). The inclusion criteria consisted of search being limited to only randomized control trials in humans published in English literature, between 2000 and 2020.
The data of the included articles were collected in the data extraction files. The fulfillment of the inclusion/exclusion criteria was decided by two independent reviewers. In case of any disagreement, the article was excluded from the study. The risk of bias was assessed for the included studies using the Cochrane Collaboration tool and the grade framework. The articles were categorized regarding the risk of bias on either “high,” “low,” and “unclear” as shown in Table 1. The articles with missing details were also excluded from the study. Figure 1 shows the flow diagram of the studies retrieved through the searching and selection process in accordance with PRISMA guidelines.
Description of studies
The search identified 1130 studies potentially relevant to the review. Based on the assessment of the title, 260 studies were retrieved for examination. Out of these, 236 studies were excluded after the abstract assessment and the remaining 24 studies were critically appraised for methodological quality for possible inclusion. Of these studies, 11 met the inclusion criteria and were included in the review. Figure 1 summarizes the study identification process. All the papers included in this review were based on clinical studies which were published between 2000 and 2020. A summary of the study design, clinical findings, and outcomes of each paper are illustrated in Table 1. The findings of these clinical studies were based either on measurement of all or most of the factors among plaque index (PI), gingival index (GI), bleeding index, pocket depth, and CAL.
Plaque index and gingival index
Out of the 11 studies included in this review, three studies investigated the PI and GI after both topical and intrasulcular application of coenzyme Q [Table 2]. Five studies measured the PI and GI after intrasulcular application of coenzyme Q and 3 studies evaluated only the PI after intrasulcular application [Table 3]. However, all the studies showed a significant difference in the PI and GI from baseline to tested period.
Bleeding on probing
The sites were also evaluated for bleeding on probing (BOP) in 9 studies, out of which 3 included both the topical and intrasulcular application of coenzyme Q. Six studies investigated BOP using only intrasulcular application of coenzyme Q [Table 4].
Periodontal pocket depth
All the 11 studies included in this review evaluated the periodontal pocket depth at baseline and test period [Table 5]. There was a significant improvement in the pocket depth in all the studies including the intrasulcular application alone as well as the application of coenzyme Q both topically and intrasulcularly.
Clinical attachment level
In the included articles, 8 studies evaluated the CAL and one study evaluated relative attachment level from baseline to test period. Seven studies among these evaluated both topical and intrasulcular application of coenzyme Q. Two of them investigated CAL using intrasulcular application only [Table 6].
Periodontitis is a series of inflammatory and immune responses to the bacteria and viruses that colonize the periodontal and associated tissues. This creates a complex bidirectional series of host–microbial interaction, which leads to a massive neutrophil migration to the gingiva and gingival fluid, leading to abnormal spreading of free radicals and ROS produced. Consequently, this led to a search for appropriate “antioxidant therapy” in inflammatory periodontal disease. Coenzyme Q10 (CoQ10) is an antioxidant that exists in an oxidized form (ubiquinone or CoQ) and a reduced form (ubiquinol or CoQH2). Due to its exceptional antioxidant properties, it has received much research attention in the last several years as an adjunctive therapy to periodontal disease either topically, intrasulcularly, or as a supplementation.
In the periodontal literature, there are number of studies which evaluated the efficacy of coenzyme Q in gingivitis and periodontitis with its different routes of administration including oral administration, topical gel form, or intrasulcular gel form. In this review, we included 11 studies which thoroughly explained the association between CoQ10 and periodontal disease by its application topically, intrasulcularly, or both. There were three studies out of 11 in which the results were evaluated after application of both intrasulcular and topical gel application. A study by Sale et al. evaluated the efficacy of CoQ10 (Perio Q gel) by topical application as well as intrasulcular application of gel combined with SRP. Results showed that there was a significant improvement in all clinical parameters in the test site, at the end of 4-week period. They also concluded that these results were probably due to cumulative effect of Perio Q gel as an antioxidant, immune enhancer, and also tissue healing accelerator. These results are consistent with a study conducted by Hans et al., which after intragroup analysis showed a significant reduction in clinical parameters in the treatment groups and after intergroup comparison showed a great improvement in clinical parameters after intrasulcular gel application combined with SRP. A clinical study by Pal et al. evaluated the efficacy of Perio Q gel as an adjunct to SRP in the management of gingivitis and periodontitis. The results showed a statistically significant improvement in clinical parameters after topical and intrasulcular gel application at the end of 2 weeks.
Topical application of CoQ10 gel is less technique sensitive than its intrasulcular application; however, the later one has more retentive ability which can improve treatment outcome. Some clinical trials showed better outcomes after the intrasulcular application of CoQ10 gel alone in areas of pockets. A study by Barakat and Attia. investigated the effectiveness of CoQ10 gel after intrapocket application combined with SRP. After 1-month evaluation, the data revealed a significant difference in the parameters when compared with sites treated with SRP alone. A similar study by Raut and Sethi. evaluated the efficacy of CoQ10 as an adjunct to SRP in smokers with chronic periodontitis after intrapocket application. The results showed a significant improvement in the clinical parameters at the end of 1- and 3-month interval. These results are in agreement with several studies. On the other hand, there are several reports consistent with these results; they demonstrated no significant difference between sites treated with or without coenzyme Q10 gel adjunct to periodontal therapy. A study conducted by Roopa et al. to test the efficacy of intrasulcular CoQ gel revealed a nonsignificant reduction for each clinical parameter on intergroup analysis between intrasulcular gel application combined with SRP and SRP alone. These results were also supported by Pranam et al., in which no statistically significant difference between clinical parameters was observed in both groups at all time intervals. They concluded that adjunctive use of CoQ 10 is not superior to SRP in the treatment of chronic periodontitis.
Researches have been conducted for clinical and immunological evaluation of CoQ10 as an adjunct to nonsurgical periodontal therapy because majority of periodontal tissue destruction is caused by an inappropriate host response to periopathogens and their products including ROS, free radicals, and MMPS. A study by Attia et al. evaluated clinical and immunologic effects of intrapocket application of CoQ10 combined with SRP. Clinical evaluation revealed a significant improvement in all parameters at baseline and 30-day posttreatment. The levels of tumor necrosis factor-alpha (TNF-a) were greatly reduced by the end of 30 days. The efficacy of CoQ gel has been compared with other antioxidants such as hyaluronic acid and tea tree oil. A study by Raut et al. compared the evaluation of CoQ gel and Melaleuca alternifolia (tea tree oil) and concluded that both of these agents have equal effective antioxidant property, but not superior to SRP alone. Another study by Sharma et al. evaluated the role of CoQ-based gel and compared it with 0.8% hyaluronic acid gel. On intergroup analysis, it was concluded that the local application of CoQ and hyaluronic acid gel in conjunction with SRP may have beneficial effect on periodontal health of patients with chronic periodontitis. Furthermore, CoQ10 showed superior improvement in gingival parameters as compared to hyaluronic acid and control group. These results were believed due to the fact that CoQ10 has been known to mediate NFkB1-dependent proinflammatory cytokine and TNF-a. These all actions contribute to resolve inflammation and promote wound healing.
Some trials supported the use of CoQ10 as a sole agent for the treatment of chronic periodontitis rather than an adjunctive therapy. A follow-up study was conducted by Salih and Mahmood for 6 weeks, in which patients were divided into three groups: the gel group (intrapocket application), combination group (SRP + intrapocket application), and SRP group. Follow-ups were assessed at 1st visit, 3rd week, and 6th week. The results suggested the possibility to use the gel as a sole agent to support standard treatment procedures in periodontitis. Thus, in this review, all the parameters as well as clinical indices in most of the trials indicate that CoQ10 when used with SRP gave added advantage as compared to sites with SRP alone.
This review summarizes that the adjunctive use of CoQ10 gel with SRP can boost the antioxidant concentration and the intrasulcular as well as topical application along with mechanical debridement has shown promising outcomes for treating periodontal diseases. Clinical research for its efficacy compared with other antioxidant agents needs to be done for designing a strategic treatment plan for chronic periodontitis patients. Further long-term clinical studies of CoQ10 gel with various dosage and duration need to be conducted. The concomitant biochemical and microbial analysis could also help in better interpretation of findings.
Few studies included in our systematic review had high risk of bias for selective reporting and incomplete data outcome.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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