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. 2024 Sep 12;36(12):1509–1514. doi: 10.1016/j.sdentj.2024.09.014

Comparative assessment of Omega-3 and CoQ10 as adjuncts to periodontal therapy and total antioxidant capacity of saliva in patients with chronic periodontitis: A double-blind, randomized clinical trial

Amirhossein Farahmand a, Marjan Talebi b,c,⁎, Farzaneh Ramezani a, Roghayeh Karami a, Zahra Jafari Nodoushani a, Neda Alsadat Ayatollahi d, Seyed Abdulmajid Ayatollahi e,⁎⁎, Arezoo Alaee f
PMCID: PMC11976097  PMID: 40952889

Graphical abstract

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Keywords: Antioxidants, Coenzyme Q10, Omega-3, Fatty acids, Saliva, Chronic periodontitis

Highlights

  • •

    The analysis of the gingival index revealed a significant reduction in inflammation within the Omega-3 group compared to both the Coenzyme Q10 and control groups.

  • •

    The bleeding on probing index within the Omega-3 group demonstrated significant improvements in reducing bleeding.

  • •

    The levels of TAC in the patients’ saliva across all three groups exhibited changes when compared to the initial measurements.

Abstract

Introduction

The dental community has shown interest in the potential of Omega-3 and coenzyme Q10 for reducing inflammation in the periodontium. These antioxidant agents may enhance the outcomes of non-surgical periodontal treatments. This study aimed to investigate the potential benefits of CoQ10 and Omega-3 supplements in improving periodontal health and the TAC of saliva in individuals with chronic periodontitis.

Methods

In a double-blind, randomized clinical trial, 75 individuals were diagnosed with chronic periodontitis. These individuals were randomly allocated into three groups. The periodontal examination involved a total of 300 teeth across the three groups. The periodontal parameters of the two molars adjacent to the mandible were measured using a periodontal probe. All patients underwent scaling and root planing. Groups A and B received CoQ10 and Omega-3 respectively, while Group C served as the control. The TAC of the non-stimulated saliva samples was evaluated to assess any changes before and after 2 months. Statistical techniques were employed to compare the CAL index and PPD between the groups under study.

Results

The analysis of the gingival index indicated a notable reduction in inflammation within the Omega-3 group compared to both the CoQ10 and control groups, with a nearly 30% decrease observed. Furthermore, the bleeding on probing index within the Omega-3 group demonstrated significant improvements when contrasted with the CoQ10 and control groups, with this decrease being statistically significant. Additionally, the levels of TAC in the patients’ saliva across all three groups exhibited changes when compared to the initial measurements.

Conclusion

These findings provide valuable insights into the potential therapeutic effects of Omega-3 and CoQ10 supplementation on periodontal health and the antioxidant capacity of saliva.

1. Introduction

Periodontitis is a complex inflammatory disease influenced by various factors that lead to periodontal tissue damage and, ultimately, tooth loss. Key influences include genetics, systemic health conditions, and lifestyle habits such as oral hygiene, smoking, stress levels, and diet (Bouchard et al., 2017, Gomes Muniz et al., 2015, Talebi Ardakani et al., 2022). Periodontitis causes tissue destruction due to the overreactivity of the patient's immune response to dysbiotic biofilm (Farahmand et al., 2019, Van Dyke, 2017). This intensified immune reaction results in increased inflammation and damage to the surrounding tissues in the mouth (Ma et al., 2024, Van Dyke, 2017).

The development of teeth and the probability of periodontal diseases are influenced by the nutrients obtained from the diet. Moreover, dietary elements can change the composition and acidity of saliva (Barnawi et al., 2023, Hajishengallis, 2015, Tonetti and Chapple, 2011, Van Der Velden et al., 2011). Periodontal tissue inflammation is characterized by infiltrations of polymorphonuclear leukocytes and macrophages, followed by phagocytosis through oxidants (Pourbagher-Shahri et al., 2021, Talebi et al., 2023, Tartaglia et al., 2017).

ROS are capable of damaging cell membranes and associated biomolecules such as DNA. A significant number of antioxidants can neutralize these harmful free radicals and ROS. Examples include lycopene, Vitamin C, and α-tocopherol (Battino et al., 1999, Gomes Muniz et al., 2015, Jomova et al., 2023, Mohideen et al., 2023, Phaniendra et al., 2015). Antioxidants are commonly used as adjuvants to neutralize excessive free radicals production in periodontal disease conditions. They are often part of adjuvant therapy along with scaling and root planning for the treatment of periodontal disease in patients. Recently, coenzyme CoQ10, a naturally occurring substance found within mitochondria, has also gained popularity (Nasoohi et al., 2019, Pitale et al., 2012).

Recent findings advocate incorporating a low-carbohydrates diet into one's lifestyle, along with increased consumption of Omega-3 fatty acids, Vitamins D and C, and fiber, to substantially reduce gingivitis and periodontal inflammation (Castro dos Santos et al., 2022, Merle et al., 2023, Rasperini et al., 2019, Woelber et al., 2016). Also, the combination of CoQ10 therapy and oral hygiene maintenance can lead to improved outcomes in periodontal treatment, whether applied directly to the affected area or taken orally (Mani et al., 2013).

The objective of this research is to compare the effects of CoQ10 supplementation to Omega-3 on periodontal parameters adjunctive to non-surgical treatment over eight weeks in patients with chronic periodontitis.

2. Materials and methods

2.1. Study groups and design

This double-blind, randomized clinical trial was performed to assess the effectiveness of CoQ10 and Omega-3 dietary supplements on the periodontal health of patients with chronic periodontitis and the TAC of their saliva after two months of supplementation. Seventy-five patients referred to the Periodontology Department of Boroujerd Dental School, affiliated with the Islamic Azad University of Medical Sciences, were selected for this study. The study adhered to the Helsinki Declaration of Ethics and was approved by the Ethics Committee of the Boroujerd Faculty of Dentistry (Code of Ethics: IR.IAU.B.REC.1402.018). The trial was registered at ClinicalTrials.gov (NCT06358963). Written informed consent was obtained from all participants, ensuring open and responsible research within ethical parameters.

Several clinical periodontal parameters were evaluated, including PI, BOP, GI, PPD, and CAL in six different areas of the tooth surface. Subsequently, SRP was performed, and oral hygiene practices were improved for all participants (Carter and Barnes, 1974, O’Leary et al., 1972, Silness and Löe, 1964, Talebi Ardakani et al., 2022). The periodontal examination involved a total of 300 teeth across the three groups.

The participants were randomly divided into three groups: Group A received 30 mg of CoQ10 daily, Group B received 200 mg of Omega-3 daily, and Group C did not receive any supplements. At the end of the two-month study period, the clinical periodontal parameters were reassessed. To evaluate changes in the TAC of saliva before and after supplement intake, as well as in the group that did not receive supplements, 2 mL of non-stimulated saliva was collected from each participant at the start and end of the study.

Furthermore, the selection of eligible participants for this study was determined by the following criteria.

2.1.1. Inclusion criteria

Participants were healthy individuals aged 28 to 35, diagnosed with Stage I chronic periodontitis, characterized by the following criteria: PD of 4 mm or less, CAL of 1 to 2 mm, and RBL no greater than 15 % (Tonetti et al., 2018). They must have molar teeth and exhibit plaque and bleeding scores below 25 %.

2.1.2. Exclusion criteria

The subjects would be excluded if they met any of the following criteria: the presence of systemic diseases, currently undergoing orthodontic treatment, pregnancy or lactation, use of medications that could affect periodontal health (e.g., antibiotics) within the past six months, history of cancer, radiotherapy, or chemotherapy within the past five years, or history of periodontal surgery in the study area within the past six months. The patients who have used medicinal supplements or smoked cigarettes or tobacco within the past six months were not considered.

2.1.3. Sample size

The sample size was determined using the two-sample t-test power analysis function of the DASS11 software (Pranam et al., 2020). The Paired Sample Difference T-test feature was utilized, with a significance level of α = 0.05 and a power of β = 0.2. The average standard deviation was calculated to be 7.4, and the minimum significant difference was set at 5 %. Consequently, the study concluded that a minimum of 25 individuals should be included in each group for participation.

2.1.4. Randomization

The randomization procedure involved patients selecting their preferred treatment type and desired treatment location through a lottery system. This was accomplished by choosing blocks of four pre-named cases (CoQ10 and Omega-3) and controls. Once the choice was registered, the corresponding treatment with the same name was administered.

2.1.5. Blinding

The research was conducted using a double-blind methodology. To ensure impartiality, both the medications for Omega-3, CoQ10, and control groups were prepared to have identical appearance, packaging, and color. To prevent bias, a clinician not associated with this present study labeled the medications as A, B, and C according to their content and distributed them to the subjects. Neither the dental clinician who recorded the clinical periodontal parameters nor the patients were aware of the group assignments. Additionally, the statistician was also blinded to the group assignments, further enhancing the study's objectivity.

2.2. Saliva sampling and TAC analysis

Saliva collection was performed prior to clinical periodontal assessments and any interventions. Patients were instructed to avoid chewing gum and consuming any food or beverages, except for water, for one hour preceding the sampling (Ghods et al., 2021). Salivary specimens were collected from all participants at the baseline and again after a two-month interval. Next, a volume of 2 mL of unstimulated saliva was collected in a 50 mL Falcon tube Patients were asked to tilt their head forward, slightly open their mouth with minimal movement, and allow saliva to passively drip into the tube. Saliva samples were then aliquoted into 1.5 mL tubes and frozen at −80 °C. The antioxidant properties and free radical scavenging capabilities were assessed using the DPPH method. The analysis was conducted using 96-well microplates, where 200 µL of a 100 mM DPPH solution in methanol was combined with 20 µL of the various saliva concentrations. The mixture was thoroughly mixed and incubated at room temperature in darkness for 30 min. Absorbance was then measured at a wavelength of 520 nm using a BioTek microplate reader (Winooski, Vermont, United States) (Gawron-Skarbek et al., 2019, Talebi et al., 2021, Yazdani et al., 2019).

2.3. Statistical analysis

Statistical methods were utilized to analyze the CAL index and PPD across the two groups involved in the study, using SPSS version 22.00 (SPSS Inc., Chicago, United States). When the data was normally distributed, a dependent sample t-test was used. Conversely, if the data was not normally distributed, a non-parametric alternative to the t-test was employed. Additionally, for comparing BOP between the two groups, the Mann-Whitney U test was used. Statistical significance was set at a threshold of (p < 0.05), ensuring that the results were meaningful within the context of the analysis.

3. Results

The clinical trial that was carried out followed a randomized, double-blind, controlled design. Among the 85 patients referred to the study, 80 met the eligibility criteria and took part in the research. After the follow-up sessions, 5 patients decided to discontinue their participation (Fig. 1). The average age of the participants was 31.3 ± 0.9, with the majority being women. Regarding the periodontal parameters, the average pocket depth in the CoQ10 group was 1.41 mm after the study period, while it measured 1.39 mm in the Omega-3 group and 1.89 mm in the control group, indicating no significant variance among the groups. Similarly, the average CAL in the CoQ10 group was 0.83 mm, 0.78 mm in the Omega-3 group, and 0.99 mm in the control group at the 2-month mark, with no significant differences observed. All three groups exhibited a reduction in plaque scores compared to the baseline measurements. The PI was similar among the three groups on the initial day, but the Omega-3 group displayed a more substantial decrease compared to the CoQ10 and control groups, showing a statistically significant distinction.

Fig. 1.

Fig. 1

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The Consort flow chart illustrates the state of the sampling process.

The analysis of the GI revealed a significant reduction in inflammation within the Omega-3 group compared to both the CoQ10 and control groups at the study's conclusion (P≤0.0001). Furthermore, the Omega-3 group showed significantly improved BOP scores, indicating reduced bleeding, compared to the CoQ10 and control groups (Table 1).

Table 1.

Comparison of periodontal parameters of the study groups at different time intervals.

Periodontal parameters
First day
(Groups) 		No. Mean ± SD Periodontal parameters
Last day (Groups) 		No. Mean ± SD P-value
PPD (mm) CoQ10 25 4.54 ± 0.58 CoQ10 25 1.41 ± 0.08 0.0001
Omega-3 25 4.53 ± 0.61 Omega-3 25 1.39 ± 0.10 0.0001
Control 25 4.55 ± 0.65 Control 25 1.86 ± 1.11 0.0001
CAL CoQ10 25 3.60 ± 0.55 CoQ10 25 0.83 ± 0.32 0.0001
Omega-3 25 3.80 ± 0.49 Omega-3 25 0.78 ± 0.38 0.0001
Control 25 3.82 ± 0.42 Control 25 0.99 ± 0.27 0.0001
PI CoQ10 25 54.40 ± 10.47 CoQ10 25 22. 28 ± 0.47 0.0001
Omega-3 25 56.33 ± 9.15 Omega-3 25 24. 22 ± 0.46 0.0001
Control 25 60.85 ± 12.81 Control 25 26. 35 ± 0.44 0.0001
BOP CoQ10 25 62.04 ± 0.14 CoQ10 25 28.09 ± 10.00 0.0001
Omega-3 25 64.02 ± 0.17 Omega-3 25 21.01 ± 12.00 0.0001
Control 25 65.03 ± 0.12 Control 25 35.01 ± 18.00 0.0001
GI CoQ10 25 2.30 ± 0.47 CoQ10 25 0.86 ± 0.16 0.0001
Omega-3 25 2.11 ± 0.33 Omega-3 25 0.62 ± 0.12 0.0001
Control 25 2.35 ± 0.49 Control 25 1.04 ± 0.10 0.0001
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Analysis of salivary antioxidant levels revealed significant changes across all three groups by considering their effects on scavenging free radicals (Table 2).

Table 2.

Comparison of TAC of the study groups at different time intervals.

Groups Mean ± SD (%)
 Groups Mean ± SD (%)
First day Last day
TAC-CoQ10 71.188 ± 14.648 TAC-CoQ10 48.356 ± 11.216
TAC-Omega-3 70.198 ± 14.747 TAC-Omega-3 55.524 ± 12.367
TAC-Control 72.561 ± 17.809 TAC-Control 67.281 ± 20.138
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4. Discussion

The present study determined that incorporating CoQ10 and Omega-3 supplements in conjunction with SRP has the potential to decrease the progression of periodontal disease by diminishing gingival inflammation.

Omega-3 polyunsaturated fatty acids have been recognized for their therapeutic potential, exhibiting anti-inflammatory effects in various health conditions such as periodontitis via attenuating inflammatory mediators and cytokines (Miroult et al., 2023, Serhan et al., 2008, Van Ravensteijn et al., 2022, Wadia, 2022)(Calder, 2006). CoQ10, an endogenous antioxidant in its reduced form, increases CoQ10 levels in the gums while concurrently reducing inflammation of the tissues that hold teeth in place (Prakash et al., 2010). Systemic CoQ10 as adjunctive therapy to non-surgical periodontal therapy showed significant improvement in gum bleeding and pocket depth (Manthena et al., 2015). Numerous studies have highlighted the advantages of CoQ10 in managing periodontal diseases (Manthena et al., 2015, Prakash et al., 2010, Sharma et al., 2016), and the present study further supports its efficacy by demonstrating a significant reduction in clinical parameters throughout the study period for each group. According to the findings of previous studies, the application of CoQ10 gel has shown promising results in improving the clinical parameters of patients with periodontitis (Hanioka et al., 1994, Raut et al., 2019, Sharma et al., 2016, Shoukheba and El- Kholy, 2019). These studies have reported a significant decrease in PPD and GI, along with an increase in adhesive surface. Furthermore, the use of CoQ10, whether topically or systemically, has demonstrated improvement in patients with chronic periodontitis, smokers, and diabetic patients with periodontitis. The application of subgingival CoQ10 has proven to be effective in reducing gingival inflammation and PPD while increasing CAL. Additionally, Hanioka et al. suggested that CoQ10 can enhance oxygenation to inflamed gingiva (Hanioka et al., 1994). A study conducted on periodontally healthy individuals found that CoQ10 supplementation resulted in a reduction in gingival bleeding, although no change in TAC was observed in the gingival crevicular fluid (Denny et al., 1999).

Various research (Kamel Shalaby and Mohammed Morsy, 2019, Stańdo et al., 2020) led to the observation of a notable decrease in bleeding during probing among the intervention group in contrast to the control group. Other scientists (Deore et al., 2014, Elkhouli, 2011, El-Sharkawy et al., 2010, McCambridge et al., 2014) reported comparable outcomes to the current findings, indicating that Omega-3 supplementation led to amendments in clinical periodontal parameters. In the studies by Martins et al. and Keskiner et al., a decrease in CAL and PD was noted in the intervention group compared with the control group, but the studies did not find any statistically significant differences between these two groups. Whereas in this study, more than 1 mm of difference in both CAL and PD was observed between the two groups, which clinically is considered significant (Keskiner et al., 2017, Martinez et al., 2014). Furthermore, the study conducted by Keskiner et al. revealed that participants who were administered Omega-3 supplements experienced a statistically significant decrease in salivary TNF-α levels, indicating a positive impact on inflammation, as well as a significant rise in salivary SOD levels, suggesting enhanced antioxidant activity. However, the current research demonstrated enhancements in clinical indicators such as PPD, CAL, PI, BOP, and GI scores, as well as TAC of saliva. These improvements can be accounted for by the fact that when the deficiency of Omega-3 and CoQ10 is amended by oral administration, there is momentous improvement in the health of the periodontium.

5. Conclusion

In conclusion, the findings of our study highlight the promising potential of using CoQ10 and Omega-3 supplements with SRP in managing periodontal disease. Analysis of the GI showed that there was a significant decrease in inflammation for the Omega-3 group in comparison with the CoQ10 and control groups. The BOP index for the Omega-3 group had significant improvements in comparison with CoQ10 and the control groups. Furthermore, the trend of TAC levels in saliva showed changes from baseline values. The results suggest that this integrative approach could significantly reduce the disease progression by mitigating GI. This innovative strategy, if further validated through extensive clinical studies, could develop the field of periodontal care, offering a more holistic and effective treatment option for patients. However, it is crucial to ensure that these supplements should be used as adjuncts to standard periodontal therapies. Furthermore, the optimal dosage and duration of supplementation need to be determined to boost benefits and minimize potential unwanted effects.

Ethical approval

The research protocol was reviewed and approved by The Ethics Committee (with the code of ethics: IR IAU.B.REC.1402.018) situated within the Faculty of Dentistry, and was subsequently recorded on clinicaltrials.gov (NCT06358963). The process of the study aligns with the fundamental tenets delineated in the Declaration of Helsinki concerning experimentation on human subjects. All participants provided both oral and written consent after being duly informed.

Funding

The current study is financially supported by the Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

CRediT authorship contribution statement

Amirhossein Farahmand: Writing – review & editing, Writing – original draft, Supervision, Project administration, Resources, Investigation, Formal analysis, Methodology, Conceptualization. Marjan Talebi: Writing – review & editing, Writing – original draft, Supervision, Resources, Methodology, Conceptualization. Farzaneh Ramezani: Investigation, Formal analysis, Methodology. Roghayeh Karami: Investigation, Formal analysis, Methodology. Zahra Jafari Nodoushani: Investigation, Writing – review & editing. Neda Alsadat Ayatollahi: Investigation, Writing – review & editing. Seyed Abdulmajid Ayatollahi: Investigation. Arezoo Alaee: Writing – review & editing, Supervision, Resources, Methodology.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

The authors express their gratitude to the participants involved in the study. The graphical abstract was developed in part using Servier Medical Art, which is licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/) and Biorender (https://www.biorender.com).

Footnotes

Appendix A

Supplementary data to this article can be found online at https://doi.org/10.1016/j.sdentj.2024.09.014.

Contributor Information

Marjan Talebi, Email: talebi.m@sbmu.ac.ir.

Seyed Abdulmajid Ayatollahi, Email: majid_ayatollahi@yahoo.com, majid_ayatollahi@sbmu.ac.ir.

Appendix A. Supplementary material

The following are the Supplementary data to this article:

Supplementary Data 1
mmc1.pdf (456.5KB, pdf)

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