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Table of Contents   
ORIGINAL RESEARCH  
Year : 2021  |  Volume : 32  |  Issue : 2  |  Page : 187-191
Efficacy of antioxidants therapy on progression of periodontal disease – A randomized control trial


1 Department of Periodontology, Government Dental College, Raipur, India
2 Department of Oral Pathology, Government Dental College, Raipur, India
3 Post Graduate Student, New Horizon Dental College and Research Institute, Bilaspur, Chhattisgarh, India

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Date of Submission11-Mar-2020
Date of Decision19-May-2020
Date of Acceptance25-Jun-2020
Date of Web Publication22-Nov-2021
 

   Abstract 


Background and Aim: Increased oxidative stress has emerged as one of the prime factors in the pathogenesis of periodontitis. Hence, antioxidant therapy may become a promising tool in the treatment of periodontal disease. Uric acid is a major salivary antioxidant, levels of which decrease in periodontitis. The aim of the present study was to investigate the effect of antioxidant therapy on the progression of periodontal disease. Material and Methods: This is a randomized controlled clinical trial conducted among 48 systemically healthy participants having generalized gingivitis with probing depth <3 mm, plaque index (PI) <1, and no bone and attachment loss. Participants were randomly assigned equally (n = 24) into two groups (test and control) using the lottery method. Full mouth scaling and root planing were performed in both the groups and oral hygiene instructions were given. Periodontal assessment at baseline 1 h after scaling and root planing was done with clinical parameters by a single examiner. Test group was prescribed; the commercially available anti-oxidant containing natural lycopene with green tea extract. Sample collection was done for both the groups at baseline and at the 45th day. Results: It was observed that significantly high results were obtained during intra-group comparison for both modified plaque index and sulcus bleeding index from baseline to 45 days. After treatment, a very highly significant increase (P ≤ 0.001) in the test group and significant (P ≤ 0.05) increase in the control group were observed in salivary uric acid levels. Conclusion: Oral lycopene and green tea extract supplementation is positively associated with salivary uric acid levels and plays an important role in the management of gingivitis.

Keywords: Antioxidant, green tea, oral lycopene, periodontitis

How to cite this article:
Wasti J, Wasti A, Singh R. Efficacy of antioxidants therapy on progression of periodontal disease – A randomized control trial. Indian J Dent Res 2021;32:187-91

How to cite this URL:
Wasti J, Wasti A, Singh R. Efficacy of antioxidants therapy on progression of periodontal disease – A randomized control trial. Indian J Dent Res [serial online] 2021 [cited 2021 Dec 8];32:187-91. Available from: https://www.ijdr.in/text.asp?2021/32/2/187/330932



   Introduction Top


Periodontium is widely affected by dental plaque; a diverse microbial community found on the tooth surface embedded in a matrix of polymers of bacterial and salivary origin.[1] If not removed regularly, plaque gets mineralized to form calculus, which in turn initiates the inflammatory process of the periodontium. This results in tooth loss and mobility. The role of personal risk factors such as poor lifestyle and negative psychosocial conditions have been said to play an important role in the aetiology of adult periodontitis.[2] It is also generally considered to result from an imbalance between potentially pathogenic microbes and the nature and efficacy of local and systemic host responses.[3] Periodontal diseases are the major dental problems affecting people worldwide as well as Indian Community.[4] The extent and severity of periodontal disease were shown to be different in different age groups.[5] The working populations in India usually belong to the lower socioeconomic groups. Workers are also involved in smoking, chewing tobacco and drinking habits, which predispose to oral diseases particularly related to gums.[6]

As the recent trend in nutrition is towards the development of healthy food in the form of 'functional food', one of the desirable properties in a dietary component is its 'antioxidant effect'. Antioxidants have gained importance in recent years due to their ability to neutralize free radicals or their actions. Antioxidants are enzymes or other organic molecules that can counteract the damaging effects of reactive oxygen species in tissues. Antioxidants can be both exogenous and endogenous, and synthetic or natural and they can be water-soluble or lipid- soluble. The term 'antioxidant' is often applied to any organic molecule that acts against the harmful effects of free radicals (molecules with unpaired electrons).[7],[8]

It is a remarkable fact that antioxidants are non-toxic compounds that reduce the incidence of cancer. Antioxidant nutrients such as vitamin E, beta-carotene, lycopene and selenium are regularly found to reduce the risk of lung, prostrate, stomach, or body cancers as well as pre-cancerous conditions.[9]

Oxidative stress occurs; when during an inflammatory response, the reactive oxygen species (ROS) overwhelm the endogenous antioxidant defence system of the body.[10],[11] ROS is generated by polymorphonuclear leukocyte in the process of oxidative burst during phagocytosis. The inflammatory process could be attenuated by exogenous antioxidants in the form of dietary supplements, which strengthens the body's antioxidant defence system. However, current evidence-based guidelines provide sparse recommendations for the nutritional management of participants with periodontal disease.

Lycopene is an effective natural antioxidant and most efficient biological carotenoid exhibiting highest physical quenching rate with singlet oxygen (twice as high as that of beta-carotene and ten times higher than that of α-tocopherol)[12] It reverses the DNA damage induced by hydrogen peroxide. Serum and tissue lycopene levels are inversely related to chronic disease risk. Lycopene participates in a cascade of chemical reactions, protecting critical cellular biomolecules, including lipids, proteins, and DNA and believed to reduce the risk of cardiovascular disease, cancer, osteoporosis, and in some cases, even male infertility.

Green tea contains many polyphenolic components known as catechins such as epigallocatechin gallate (EGCG) and epigallocatechin, which possess higher antioxidant activity than Vitamin C and E. Their antioxidant action involves the scavenging of ROS or chelation of transition metals while indirectly, they upregulate Phase II antioxidant enzymes.[13] Catechin has been shown to inhibit the growth of Porphyromonas gingivalis, Prevotella intermedia, and Prevotella nigrescens and the adherence of P. gingivalis onto human buccal epithelial cells in in vitro studies.[14] Recently, EGCG (Epigallocatechin gallate) has been shown to downregulate the activity and expression of matrix metalloproteinases (MMPs) as MMP-2 and MMP-9 (collagenase and gelatinase) by suppressing the phosphorylation of extracellular signal-regulated kinase involved in mitogen-activated protein kinase pathway. In addition, green tea may restrict bone loss in periodontitis patients as EGCG has been shown to inhibit the osteoclast formation and it induces the apoptotic cell death of bone-resorbing osteoclast cells in a dose-dependent manner.

Now evidence are emerging to implicate these increased free radicals (FR) in the pathogenesis of periodontitis as it enhances tissue destruction.[15] Uric acid is a major salivary antioxidant, levels of which decrease in periodontitis.[16] The aim of the present study was to investigate the effect of antioxidant therapy on the progression of periodontal disease.


   Material and Methods Top


This is a prospective, randomized, controlled clinical trial study conducted in 48 systemically healthy participants having generalised gingivitis with probing depth <3 mm, plaque index (PI) <1, and no loss of attachment and bone loss assessed radiographically with orthopantamograph. The sample size was determined before the study by a statistician. Ethical approval was obtained from the Institutional Review Board of the college committee on human studies. All participants received detailed information on the study and informed written consent was read and signed, after fulfilling the selection criteria. Patients with systemic diseases, the habit of smoking and pan chewing, subjects on medications like antibiotics and antioxidants were excluded from the study.

Participants were randomly assigned equally (n = 24) into two groups (test and control) using the lottery method. Full mouth scaling and root planing were performed in both the groups and oral hygiene instructions were given. Ideally scaling is a treatment option for gingivitis but to remove subgingival calculus root planing was performed. Periodontal assessment at baseline 1 h after scaling and root planing was done with clinical parameters (modified Quigley – Hein PI[17] and sulcus bleeding index (SBI)[18] by a single examiner. The modified Quigley – Hein PI provided a comprehensive method for evaluating plaque control procedures adopted by participants and SBI indicated gingival inflammation. The test group was prescribed, the commercially available anti-oxidant, CLIK® (Idem Healthcare Pvt. Limited) containing natural lycopene (16 mg) with green tea extract (300 mg). The patient was instructed to take the capsule once daily for 45 days as per the recommended dose. Post-operative clinical parameters and uric acid estimation in saliva samples were done after 45 days by the same examiner who was trained before to obtain validity and reliability of clinical parameters (Cronbach's alpha = 0.76).

Clinical evaluation

Modified Quigley-Hein PI (Turesky S et al.,) and SBI were recorded at six sites per tooth using a primary care provider University of North Carolina 15 periodontal probe (Hu-Friedy, Chicago, IL, USA) at baseline (1 h after scaling and root planing) and after 45 days.

Saliva collection

Sample collection was done for both the groups at baseline and at the 45th day. From each patient, 5 mL of unstimulated saliva (to avoid dilution of saliva) was collected in sterile saliva collecting bottles by allowing saliva to passively flow into them. All samples were stored at 2°C–8°C in air-tight containers.

Statistical analysis

The recorded data was compiled and entered into a spreadsheet computer program (Microsoft Excel 2007) and then exported to the data editor page of SPSS version 15 (SPSS Inc., Chicago, Illinois, USA). Descriptive statistics included computation of percentages, means and standard deviations. The statistical tests applied for the analysis were Pearson's Chi-square test (χ2), t-test, One-way Analysis of Variance and Stepwise multiple linear Regression analysis. For all tests, confidence level and level of significance were set at 95% and 5%, respectively.


   Results Top


[Table 1] and [Table 2] describe Intragroup comparison of test and control group for modified plaque index and sulcus bleeding index immediately after scaling and root planing (baseline) and at 45th day after scaling and root planing and after antioxidant supplementation (post-treatment) by paired t-test. It was observed that significantly high results were obtained during the intra group comparison for both modified plaque index and sulcular bleeding index from baseline to 45 days.
Table 1: Intragroup comparison of test and control group for modified plaque index immediately after baseline and at 45th day after scaling and root planing and antioxidant supplementation

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Table 2: Intragroup comparison of test and control group for sulcus bleeding index immediately after baseline and at 45th day after scaling and root planing and antioxidant supplementation

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After treatment, a very highly significant increase (P ≤ 0.001) in the test group and significant (P ≤ 0.05) increase in the control group were observed in salivary uric acid levels [Table 3].
Table 3: Intragroup comparison of test and control group for uric acid level (mg/dL) in saliva immediately after baseline and at 45th day after scaling and root planing and antioxidant supplementation

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Intergroup comparison between test and control group was done using an unpaired t- test. The difference in mean scores of modified Quigley – Hein PI and SBI was significantly higher (P ≤ 0.001) in the test group as compared to the control group, depicting a greater improvement in gingival status of test than control group. Post-treatment salivary uric acid levels were significantly higher (P = 0.001) in the test group, demonstrating an enhanced antioxidant profile on receiving systemic antioxidants compared to the control group without antioxidant supplements.


   Discussion Top


Antioxidant therapy is emerging as a promising new paradigm as prophylactic and therapeutic agents. These are those agents, which scavenge free radicals and ROS and prevent the damage caused by them. Antioxidants can be classified on the basis of their mode of action (preventative or scavenging), location (intracellular, extracellular or membrane- associated) and solubility (water or lipid-soluble).

Inflamed periodontal tissue produces significant amounts of pro-inflammatory cytokines, mainly IL-1, IL-6, PGE2 and tumour necrosis factor alpha (TNF-α), ROS enzymes, proteins, host cells, ions, hormones, and markers of oxidative stress and antioxidant.[19] ROS play crucial roles in normal physiological processes including response to growth factors, the immune response, and apoptotic elimination of damaged cells, but are also highly toxic and destructive when generated during the respiratory burst as it represents an important pathogenic mechanism for tissue damage and diseases associated with phagocytic infiltration. The most widely accepted risk factor is the periodontal biofilm that forms on the teeth in the absence of effective oral hygiene. Antioxidant therapy is emerging as a promising new paradigm as prophylactic and therapeutic agents. These are those agents, which scavenge free radicals or ROS and prevent the damage caused by them.[20]

Antioxidant effects of lycopene and green tea have been shown to have beneficial effects on periodontal health as it reduces oxidative stress, improves the antioxidant status and decreases markers of inflammation.[21],[22]Green tea and lycopene have proved effective in periodontitis patients when used as topical agents.[23] Behfarnia et al. showed that the green tea chewing gum improved the SBI and approximal PI and effectively reduced the level of interleukin -1β in participants with gingivitis.[24] In an in vitro study, Gadagi et al. revealed a reduction in pocket probing depth and clinical attachment level in the group receiving green tea extract as local drug delivery. Furthermore, the prevalence of P. gingivalis reduced from baseline (75%) to 4th week (25%).[25]

In the present study saliva was used as a diagnostic fluid because it can be collected in a safe and easy way requiring no special training. Whole saliva is a mixture of oral fluids, and includes secretions of the major and minor salivary glands, in addition to constituents of non-salivary origin derived from GCF, expectorated bronchial secretions, serum and blood cells from oral wounds, as well as bacteria and bacterial products, viruses and fungi, desquamated epithelial cells and food debris.[26] Uric acid is one of the major radical scavengers within plasma, urine and saliva. Uric acid levels were evaluated in the present study to determine if the administration of antioxidant increases the levels of antioxidant present in saliva, which may combat the periodontal tissue destruction caused by free radicals.

In the present study, we found a direct positive correlation between periodontal health and adjunctive antioxidant supplementation (lycopene + green tea extract) with non-surgical therapy (scaling and root planing). Improvement in clinical parameters was found to be statistically significant in both groups following therapy compared to baseline. although scaling and root planing is a standard means of controlling inflammation,[27] the improvement in test group receiving antioxidant therapy was statistically significant (P = 0.001) and greater as compared to the control group. These results are in accordance with earlier studies, which have reported an inverse association between periodontal disease and antioxidant (lycopene and green tea) intake.[28],[29],[30],[31],[32],[33] Supplementation with lycopene and green tea reported a reduction in mean pocket depth, mean clinical attachment level, bleeding on probing and halitosis.[34],[35],[36]

A decrease in concentration of uric acid levels in saliva with an increase in severity of periodontal disease was observed similar to a study by Scully et al.[37] In the present study, we found that supplementation with lycopene and green tea extract resulted in an increase in mean salivary uric acid levels. In a recent systemic review, Zhang et al. concluded that drinking green tea might be positively associated with the serum uric acid level; however, current literature does not provide enough evidence establishing this hypothesis.[38] On the contrary, some authors demonstrated the inverse relation of uric acid levels with circulating carotenoids including lycopene and green tea.[27],[39],[40]


   Conclusion Top


Within the limitations of this study, it was concluded that oral lycopene and green tea extract supplementation is positively associated with salivary uric acid levels and plays an important role in the management of the periodontal disease. The focus should not be on treating various diseases with anti-oxidants, but on the intake of a balanced diet with emphasis on antioxidant-rich fruits, vegetables, nuts, whole grains as has been recommended for the general population. Therefore, further studies should be conducted to know the beneficial role of an antioxidant in the oral cavity, as we know it change the scenario the treatment related to non-cure diseases i.e., oral cancer and periodontium.

It is recommended that further similar case-control longitudinal clinical trials with a higher number of sample sizes may be needed to corroborate the findings of this specific study to evaluate the time needed for antioxidant action.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Correspondence Address:
Dr. Ritunja Singh
Post Graduate Student, New Horizon Dental College and Research Institute, Bilaspur, Chhattisgarh - 495 001
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijdr.IJDR_227_20

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