Perspective Chapter: Antioxidants as an Adjuncts to Periodontal Therapy

Abstract

It has been established that periodontal diseases are related with the hyperactivity of neutrophils. Reactive oxygen species are produced mainly by neutrophils. In order to maintain the balance with reactive oxygen species, the need for antioxidants is increasing. As for supplements to the conventional periodontal therapy, different antioxidants have been applied in an attempt to provide new possibilities in the periodontal treatment. This chapter focused on recent studies that used different antioxidants as adjuncts to conventional periodontal treatments.

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1. Introduction

The most important immune response against periodontal pathogens attacks includes an increase in the numbers of neutrophils seen in gingival crevicular fluid (90%), junctional epithelium (50%), and connective tissue.

In order to control bacterial invasion, neutrophils have numerous mechanisms, which include extracellular and intracellular, non-oxidative, and oxidative killing mechanisms [1]. When macrophages and neutrophils are stimulated, they generate a “respiratory burst”, which is characterized by a rise in the consumption of oxygen, Hexose-Monophosphate shunt activation, and generation of Reactive Oxygen Species (ROS) and Free Radicals (FR). There is significant overproduction of FR and reactive species at sites of chronic inflammation, including periodontal diseases. Figure 1 shows the mechanisms of increased ROS production in periodontal disease.

Figure 1.

Reactive oxygen species production in periodontal disease. Nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase, hydroxyl radical (•OH), hypochlorous acid (HOCl) and singlet oxygen (1O2) [2].

Free radical may be defined as a molecular or atomic group capable of free existence with one or more unpaired electrons in its composition [3]. At low concentrations, these FRs are involved in performing a variety of cell signaling functions but at elevated concentrations, they react with certain cellular components such as proteins, DNA, and lipids, exerting oxidative stress in the periodontal ligament, gingival tissues, and alveolar bone associated with tissue damage.

Antioxidants define as the agents that scavenge ROS or FR; therefore, they prevent damage associated with them. Based on their mode of function, antioxidants can be categorized into two groups [4]. The first one includes preventive antioxidants which involve enzymatic antioxidants such as catalase (CAT), superoxide dismutase (SOD), DNA repair enzymes, glutathione reductase, and, glutathione peroxidase (GPx) as well as some metal ion sequestrators such as albumin. The second group involves chain-breaking antioxidants or scavenging antioxidants such as carotenoids (including retinol-vitamin A), ascorbic acid (vitamin C), a-tocopherol (vitamin E), polyphenols (flavonoids), reduced glutathione, and uric acid, Table 1 shows types of antioxidants.

Preventive antioxidants	Scavenging antioxidants
Catalase	Carotenoids
Superoxide dismutase	Ascorbic acid
DNA repair enzymes	Tocopherol
Glutathione reductase	Polyphenols
Glutathione peroxidase	Reduced glutathione
Metal ion sequestrators	Uric acid

Table 1.

Types of antioxidants.

Many studies have tried to detect the uses of antioxidants in the management of periodontitis because antioxidants are associated with a strong defense function against ROS. It has been concluded that enhanced clinical periodontal parameters, lower levels of systemic and local ROS as well as higher activities of systemic and local antioxidants in comparison with usual periodontal treatment resulted from periodontal treatments that are supplemented with antioxidants like lycopene, vitamin C, and vitamin E [5, 6, 7].

Muniz et al. performed a review and they examined the effects of the supplemental application of vitamin C, lycopene, vitamin E, capsules with fruits/vegetables/berry and dietary changes on periodontal treatment [8]. It established that only the use of vitamin E and lycopene is related with improved clinical periodontal parameters [8]. These results are associated with a beneficial effect not only on periodontal status but also on systemic oxidative status.

2. Methodology

For the assessment of the association between antioxidant and periodontal diseases all available studies that we could find were included. PubMed, Scopus, and Google Scholar were searched to select appropriate papers. The following combinations of search terms were used: “periodontal disease” OR “periodontitis” OR “periodontal therapies” OR “antioxidants” OR “periodontitis AND antioxidants” OR “periodontal disease AND antioxidants” OR “periodontal therapies AND antioxidant”.

Only studies written in the English language were accepted, while pilot studies and case reports were not accepted for this chapter. All reference lists of the selected studies were screened for additional papers.

3. Lycopene

Lycopene is one of the most efficient antioxidants which provides prevention against various chronic disorders, and it was found in a wide range of foods [9]. It has been classified into the class of components known as carotenoids, which are the red, yellow, and orange pigments produced by plants [10].

Lycopene is considered as the most competent biological antioxidant agent because it has the exceptional characteristic of binding to chemical groups that react with oxygen [11].

Di Mascio et al. showed that lycopene is the most effective biological carotenoid singlet oxygen quencher [12].

It has been concluded by Chandra et al. [13] and Arora et al. [5] that systemic lycopene and oral prophylaxis showed a statistically significant drop in Gingival index, compared to the placebo oral prophylaxis group. Patients were followed up in both studies for 2 weeks in gingivitis patients and 2 months in chronic periodontitis patients respectively.

Kaur et al. evaluated the influences of systemically administered extracts of piperine, curcumin, and lycopene as an adjunct to conventional periodontal treatment in patients with moderate gingivitis. They recognized a reduction in gingival index, plaque index, and bleeding scores with statistically significant differences between the control and the test groups at the 21st day period [14].

4. Vitamin C

For a long period of time, the importance of ascorbic acid (vitamin C) for periodontal health was known. In the eighteenth century, sailors often suffered from scurvy, the disease of vitamin C deficiency, associated with loosening of the teeth and bleeding of the gums. James Lind in 1747 performed his classic experiments aboard the ship “the Salisbury”; he cured scurvy with lemons and oranges in this experiment [15].

Vitamin C is considered as an important dietary nutrient that is essential as a cofactor needed by numerous enzymes. As well as vitamin C is considered as an electron donor and this characteristic accounts for every identified function of vitamin C. In addition, vitamin C is a strong water-soluble antioxidant in humans by its electron donor property. It has been suggested by many lines of studies that vitamin C is a potent antioxidant in vitro [16]. Although records from clinically controlled trials have not confirmed that elevated consumption of ascorbic acid only will assist in the protection against chronic pathological conditions, however, the verification that vitamin C is considered as an essential antioxidant in several body tissues is persuasive [17].

Even though the precise function of ascorbic acid insufficiency in periodontitis is not well recognized, ascorbic acid is considered as a candidate for handling periodontal diseases for a long period of time [18]. It has been identified that supplemental ascorbic acid is necessary for tissue regeneration and infectious diseases, however, low ascorbic acid intake does not cause periodontitis [19].

Collagen fibers, which are present in different forms of the periodontal ligament, connective tissues, and bone, depending on vitamin C for synthesis as well as other intercellular substances depend on it [20]. In addition, vitamin C has immune-regulatory role in affecting the vulnerability of the body to infectious diseases [21].

Sulaiman and Shehadeh [22], found that the supplemental dose of ascorbic acid did not provide additional improvements in comparison to non-surgical periodontal therapy alone. They attributed their finding to the possibility that vitamin C is considered as a poor antioxidant in vivo and its antioxidant activity could have no physiologic function, or its function could be inconsiderable. As well as they supposed that the antioxidant functions of ascorbic acid occur only at particular locations and may be particular to definite reactions [22].

Shimabukuro et al. [23] used dentifrice containing L ascorbic acid 2-phosphate magnesium salt, they found that gingival redness and gingival index significantly decreased in the test group in comparison with the control group [23].

Rajaram et al. evaluate the effects of a diet rich in antioxidants, vitamin C, and fiber on clinical outcomes in patients with gingival inflammation for 1 month. They concluded that gingival inflammation is significantly reduced with a diet rich in antioxidants, vitamin C, and fibers [24]. However, interventional studies, evaluating vitamin C alone, are necessary for proper evaluation of the nutritional impact on periodontal status.

5. Vitamin E

Vitamin E is a well-known antioxidant that prevents the production of ROS formed from fat oxidation [25]. Vitamin E gained its antioxidant effects by its incorporation into cellular membranes, where it inhibits the peroxidation of lipids [26, 27].

Rattanasuan et al. [28] studied the adjunctive use of vitamin E supplementation (vitamin E soft gel 200 mg/day) to the conventional periodontal therapy and they found that antioxidant defense, as well as periodontal healing, were improved [28].

6. Melatonin

It has been reported by several studies that melatonin is considered as an active component with antioxidant properties [29]. It is secreted mainly by Pinealocytes; it is a derivative of tryptophan (indoleamine) [30]. Regulation of the sleep cycle is the main function of melatonin. In addition, studies showed that melatonin is involved in energy metabolism and homeostasis [31].

Melatonin has the ability to activate brown adipose tissue and consequently increase energy expenditure. Furthermore, another research pointed out its immunomodulatory, anti-inflammatory, and antioxidant properties [32]. Melatonin can enhance the expression of antioxidant enzymes (CAT, GPx, and SOD) as well as scavenges free radicals [33].

Javid et al. investigated the anti-inflammatory and antioxidant properties of melatonin in patients with periodontal disease and type 2 diabetes mellitus (T2DM) who experience non-surgical periodontal therapy, they found that the adjunctive effects of melatonin and nonsurgical periodontal therapy may improve antioxidant and inflammatory parameters in T2DM patients with periodontal disease [34].

7. Green tea

Green tea is associated with active ingredients, which include polyphenols. The majority of them are catechins (flavan-3-ols). Furthermore, entire green tea has other antioxidants in the structure of vitamins, such as tocopherols, ascorbate and carotenoids [35].

The mechanism of action of polyphenols as antioxidants is summarized via the stimulation of antioxidant enzymes for example superoxide dismutase and glutathione S-transferase.

In a study performed by Kushiyama and co-workers, they showed that when green tea is taken regularly, it has a protective outcome. Green tea may even decrease the development of existing periodontitis [36].

Generally, green tea catechins have anti-bacterial properties besides their antioxidant properties by their actions on pathological periodontal bacteria such as Prevotella intermedia and Porphyromonas gingivalis. Inhibition of cysteine proteases of P. gingivalis is considered as the mechanism of action [37, 38].

Kudva et al. [39] and Chava and Vedula [40] used green tea as a supplementary to nonsurgical periodontal therapy and they follow the patients for a period of 21 days and 4 weeks respectively, and they found declines in probing pocket depth parameters in test groups with statistically significant differences in comparison to control groups [39, 40].

8. Discussion

This chapter evaluated the efficacy of antioxidants as an adjunct to scaling and root planing. It has been concluded that systemic lycopene and oral prophylaxis showed a statistically significant drops in clinical periodontal parameters [5, 13, 14].

Although vitamin C has a strong effect on gingival parameters and gingival health conditions, some studies showed that there is no benefit from using vitamin C as an adjunct to periodontal therapy this maybe due to the weak antioxidant capacity of vitamin C in vivo [22].

Adjunctive use of both vitamin E and melatonin in the conventional periodontal therapy results in an improvement in antioxidant defense and periodontal healing [28, 34].

Green tea not only decreases the development of existing periodontitis but also when used as supplementary to nonsurgical periodontal therapy, it resulted in a drop in periodontal parameters.

Although antioxidants have a wide range of beneficial effects for overall health, numerous studies have raised doubt about possible side effects. It has been shown that antioxidants may have a harmful effect in the development of lung cancer [41]. The antioxidants reduced the expression of p53, a key tumor suppressor protein. However, further studies are required to improve a procarcinogenic role of antioxidants.

9. Conclusion

Uses of antioxidants as an adjunct to periodontal treatment is not a new concept. Nearly all of the evaluated studies showed that there was an improvement in clinical periodontal parameters when using antioxidants as an adjunct to periodontal treatment.