*1.1.2.6 Coenzyme Q10*

*Gingival Disease - A Professional Approach for Treatment and Prevention*

*1.1.2.2 Vitamin C*

*1.1.2.3 Vitamin E*

*1.1.2.4 Polyphenols*

*1.1.2.5 Flavonoids*

Vitamin A is an important vitamin involved in vision. Vitamin A is soluble in fat, helps maintaining healthy tissues and skin, strengthens the immune system, and is necessary for a healthy bone structure. It also acts as an antioxidant, protects cells against cancer and other diseases, slows down the aging process, and helps to store fat. In vitamin A deficiency, dermatological, mucosal, and ocular changes may occur [41].

Vitamin C is a water-soluble antioxidant, which is found in citrus fruits, potatoes, tomatoes, and green leafy vegetables [5]. Since it is water soluble, it is not stored in the body, and its excess amounts are excreted through sweat and urine. Therefore, it must be taken daily [42]. Vitamin C is necessary for biosynthesis, structural integrity, and stability of many components in the connective tissue [43]. The function of vitamin C is particularly important in wound healing and tissue regeneration due to its role in collagen synthesis. Vitamin C acts as a coenzyme for many enzymes involved in the synthesis of collagen, carnitine, and neurotransmitters [2].

Vitamin C (also known as ascorbic acid) has many functions such as strengthening the immune system and development of bone and teeth. It enables protection against cancer and heart diseases. Unlike many other antioxidant vitamins, it is a water-soluble vitamin. It functions with glutathione in vitamin E regeneration. A negative correlation was found between plasma vitamin C and clinical attachment loss levels [44].

Vitamin E is a name given to identify a group of eight natural compounds consisting of various tocopherols and tocotrienols, such as α, β, and δ. The form of vitamin E with the highest biological activity is α-tocopherol [45]. Vitamin E (also known as tocopherol) is the most important oil-soluble antioxidant found in nature [46]. It contains alpha, beta, gamma, and delta tocopherols. It is stored in the liver and has many functions in the immune system. It is found in cell membranes and as a component of lipoproteins [47]. Vitamin E is a major chain-breaking antioxidant and is the first line of defense against lipid peroxidation by protecting cell membranes during the early stages of free radical attack [48]. Its function as an antioxidant is mainly to inhibit peroxidation of membrane phospholipids and prevent damage to cell membranes. Lipid peroxidation is common in membranes, erythrocytes, lipoproteins, brain, and

other tissues where polyunsaturated fatty acids (PUFAs) are abundant [47].

antiviral, antiaging, anticarcinogenic, and antioxidant properties [50].

In an experimental study in rats, vitamin E has been shown to be important in preventing alveolar bone destruction. The effect of vitamin E in reducing periodontal inflammation can be explained by the fact that it is a prostaglandin inhibitor [6, 49].

Polyphenols are composed of 4000 compounds in 13 classes (flavonoids, phenolic acids, anthocyanins, catechins, flavones, flavonols, flavanones, isoflavones, lignans, proanthocyanidins, procyanidins, resveratrol, and tannins). They are abundant in green tea, grape, and soy. They have anti-inflammatory, antiallergic,

Flavonoids are free radical scavengers and are sub-grouped into flavanones, flavanols (e.g., Luteolin), flavanols (e.g., quercetin and kaempferol), flavan-3-ols (e.g., catechin), anthocyanins, and isoflavones according to their chemical

**116**

Coenzyme Q10, also known as ubiquinone, is a naturally occurring substance and is found in all living cells. It is abundant in veal, fish, and chicken [53]. It constitutes an important part of the energy production system of the body. Coenzyme Q10 strengthens the immune system by increasing immune resistance. It also protects the body against free radicals. It is especially important for the correct functioning of the heart muscle. It is a nutritional supplement that is soluble in fat and has an effect similar to vitamin E. In addition to its antioxidant effect, it is involved in the proper functioning of the circulatory system [54].

Coenzyme Q10 levels have been shown to be relatively low in gingival tissues of individuals with periodontitis. Local or systemic administration of Coenzyme Q10 during treatment helps reduce inflammation in periodontal tissues [55].

#### *1.1.2.7 Selenium*

Selenium is found in the structure of selenoproteins and glutathione peroxidase, which is an important antioxidant enzyme. Selenoproteins help to regulate thyroid function and have a role in the immune system. Although selenium is a basic mineral required for a healthy body, the body only needs trace amounts of this mineral [56].

### **1.2 Periodontal diseases**

Periodontal diseases are inflammatory diseases characterized by inflammation and loss of periodontal tissues. Periodontopathogenic bacteria and their products are important in its etiology. The course of the disease is determined by the interaction between the periodontopathogenic bacteria and the host immune response. Reactive oxygen species play a role in these interactions in favor of tissue destruction [57]. Oxidative stress plays an important role in the pathogenesis of many diseases such as rheumatoid arthritis and atherosclerosis, and it has also been reported to affect the pathogenesis of periodontal diseases [58]. In the case of periodontal disease, the increased PMN count and activity cause a high rate of ROS release. This causes increased oxidative stress in periodontal tissues [6]. ROS produced on the surfaces of osteoclasts may play an important role in alveolar bone resorption [59]. Periodontal tissues require adequate levels of antioxidants to prevent tissue damage caused by reactive oxygen species. Therefore, some studies have focused on the effects of antioxidant use in addition to SRP (scaling and root planning) on periodontal tissue destruction [60]. Natural antioxidants protect the tissues against tissue damage caused by free radicals and play a critical role in maintaining the tissue health [61]. Due to the likely benefits of antioxidants against periodontitis, the intake of such nutrients is recommended [60]. **Figure 3** shows the possible oxidative stressmediated inflammatory pathways related to periodontal tissue breakdown [62].

In a study, a positive correlation was found between the improvement in sulcus bleeding scores and the intake of grapefruit that leads to an increase in plasma

#### **Figure 3.**

*Possible oxidative stress-mediated inflammatory pathways related to periodontal tissue breakdown. LPS, lipopolysaccharide; GM-CSF, granulocyte-macrophage colony-stimulating factor; IL8, interleukin-8; TNF-α, tumor necrosis factor-alpha; PDL, periodontal ligament; NF-κβ, nuclear factor-kappa B; ROS, reactive oxygen species; PMNL, polymorphonuclear leukocyte; TIMP, tissue inhibitor of metalloproteinases; and MMP, matrix metalloproteinase.*

vitamin C levels [63]. In an 8-month follow-up study on individuals with periodontitis, encapsulated fruit and vegetable powder concentrate was reported to reduce the periodontal pocket depth compared to placebo [64].

#### **1.3 Antioxidant micronutrients**

Main antioxidant sources in a diet are cereals, fruits, vegetables, chocolates, oils, and beverages such as tea, coffee, wine, and fruit juices [65].

#### *1.3.1 Vitamin C*

Leggott et al. [66] showed that ascorbic acid deficiency is not associated with the mucosal pathoses or changes in plaque accumulation or probing depths. In another study, the same researchers showed that vitamin C was not associated with plaque accumulation, pocket depth, and attachment loss [67]. But, in both studies, ascorbic acid status was found directly related to the measures of gingival inflammation [66, 67]. Nishida et al. [68] found a weak but statistically significant inverse relationship between the vitamin C-rich diet and the periodontal disease. Chapple et al. [2] found a strong inverse relationship between the serum vitamin C levels and the prevalence of periodontitis. Jacob et al. [69] found that normal and high doses of vitamin C intake reduced gingival inflammation and sulcus bleeding. Rai et al. [70] found a strong relationship between the low concentrations of vitamin C in serum and saliva and the risk of periodontal disease. In other studies, vitamin C levels in the gingival fluid were found to be 3-folds higher than that of plasma [71], and vitamin C was found to inhibit neutrophil collagenase activation [72]. In an experimental periodontitis study on rats, vitamin C intake decreased interleukin-1a and interleukin-1β gene expression by more than twofolds compared to the control

**119**

serum TNF-α levels.

*Antioxidants and Periodontal Diseases DOI: http://dx.doi.org/10.5772/intechopen.81815*

periodontal disease in elderly individuals [78].

found to accelerate gingival wound healing [82].

lower in patients with moderate to severe periodontitis.

the alveolar bone destruction in periodontal diseases.

*1.3.2 Vitamin E*

*1.3.3 Carotenoids*

group [73]. In the same study, an increase in plasma vitamin C levels by 175% was found to result in a significant decrease in gingival 8-hydroxydeoxyguanosine levels

In a study on rats, Sanbe et al. [74] showed that vitamin C decreased high cholesterol diet-induced alveolar bone resorption and decreased periodontal tissue damage. Vitamin C has been shown to decrease the cytotoxic and apoptotic effects of

Akman et al. [76] showed that the administration of vitamin C with or without alpha lipoic acid was associated with a significant decrease in serum myeloperoxidase levels, increased bone alkaline phosphatase levels, decreased alveolar bone resorption, and decreased RANKL-positive cell count. In individuals with chronic periodontitis, vitamin C intake in addition to nonsurgical periodontal treatment has been shown to decrease the gingival bleeding index levels [77]. Furthermore, it was reported that low serum levels of vitamin C and vitamin E may be risk factors for

Research on the relationship between vitamin E and periodontal diseases showed

conflicting results. Cohen et al. [79] reported that 5% topical vitamin E gel, in addition to SRP, did not positively affect the formation of plaque and healing of the periodontal tissues. In another study, same researchers showed that vitamin E has a protective role against bone loss [49]. Another study reported that there was no statistically significant difference between the periodontitis patients and the healthy group in terms of serum vitamin E levels [80]. These contradictory results may be related to the study design, the dose of vitamin E, and the investigated different parameters. In a study on rats, the combination of vitamin E and selenium has been shown to reduce collagen degradation [81]. In addition, vitamin E supplementation has been

A negative correlation was found between serum α-tocopherol levels and the severity of periodontitis. While the level of α-tocopherol increases, the severity of periodontitis decreases [83]. The use of vitamin E in addition to nonsurgical periodontal treatment has been shown to have positive effects on periodontal parameters [84].

Carotenoids are highly potent antioxidants. Linden et al. [85] showed that α-carotene, β-carotene, β-cryptoxanthin, and zeaxanthin levels were significantly

It has been shown that β-cryptoxanthin stimulates bone formation and may stop bone resorption by inhibiting gene expression of osteoclastic enzymes associated with bone resorption [86]. Therefore, it has been suggested that β-cryptoxanthin may reduce the risk of osteoporosis [87]. This may mean that it can slow and/or stop

Systemic supplementation of 8 mg/day of lycopene was reported to decrease the gingival index in patients with gingivitis [88]. In individuals with chronic periodontitis, it was reported that the supplementation of 4 mg/day of oral lycopene in addition to SRP for 2 weeks resulted in a reduction in clinical attachment loss [89]. Arora et al. [90] found that, in individuals with CP, 8 mg/day of oral lycopene intake for 2 months in addition to SRP had positive effects in plaque index, modified gingival index, probing bleeding, and saliva IL-1β compared to the control group but reported that there was no significant difference in terms of a reduction in pocket depth, clinical attachment, and

and a significant increase in reduced oxidized glutathione amounts [73].

*Porphyromonas gingivalis (P. gingivalis)* on gingival fibroblasts *in vitro* [75].

#### *Antioxidants and Periodontal Diseases DOI: http://dx.doi.org/10.5772/intechopen.81815*

group [73]. In the same study, an increase in plasma vitamin C levels by 175% was found to result in a significant decrease in gingival 8-hydroxydeoxyguanosine levels and a significant increase in reduced oxidized glutathione amounts [73].

In a study on rats, Sanbe et al. [74] showed that vitamin C decreased high cholesterol diet-induced alveolar bone resorption and decreased periodontal tissue damage.

Vitamin C has been shown to decrease the cytotoxic and apoptotic effects of *Porphyromonas gingivalis (P. gingivalis)* on gingival fibroblasts *in vitro* [75].

Akman et al. [76] showed that the administration of vitamin C with or without alpha lipoic acid was associated with a significant decrease in serum myeloperoxidase levels, increased bone alkaline phosphatase levels, decreased alveolar bone resorption, and decreased RANKL-positive cell count. In individuals with chronic periodontitis, vitamin C intake in addition to nonsurgical periodontal treatment has been shown to decrease the gingival bleeding index levels [77]. Furthermore, it was reported that low serum levels of vitamin C and vitamin E may be risk factors for periodontal disease in elderly individuals [78].

#### *1.3.2 Vitamin E*

*Gingival Disease - A Professional Approach for Treatment and Prevention*

vitamin C levels [63]. In an 8-month follow-up study on individuals with periodontitis, encapsulated fruit and vegetable powder concentrate was reported to reduce

*Possible oxidative stress-mediated inflammatory pathways related to periodontal tissue breakdown. LPS, lipopolysaccharide; GM-CSF, granulocyte-macrophage colony-stimulating factor; IL8, interleukin-8; TNF-α, tumor necrosis factor-alpha; PDL, periodontal ligament; NF-κβ, nuclear factor-kappa B; ROS, reactive oxygen species; PMNL, polymorphonuclear leukocyte; TIMP, tissue inhibitor of metalloproteinases; and MMP,* 

Main antioxidant sources in a diet are cereals, fruits, vegetables, chocolates, oils,

Leggott et al. [66] showed that ascorbic acid deficiency is not associated with the mucosal pathoses or changes in plaque accumulation or probing depths. In another study, the same researchers showed that vitamin C was not associated with plaque accumulation, pocket depth, and attachment loss [67]. But, in both studies, ascorbic acid status was found directly related to the measures of gingival inflammation [66, 67]. Nishida et al. [68] found a weak but statistically significant inverse relationship between the vitamin C-rich diet and the periodontal disease. Chapple et al. [2] found a strong inverse relationship between the serum vitamin C levels and the prevalence of periodontitis. Jacob et al. [69] found that normal and high doses of vitamin C intake reduced gingival inflammation and sulcus bleeding. Rai et al. [70] found a strong relationship between the low concentrations of vitamin C in serum and saliva and the risk of periodontal disease. In other studies, vitamin C levels in the gingival fluid were found to be 3-folds higher than that of plasma [71], and vitamin C was found to inhibit neutrophil collagenase activation [72]. In an experimental periodontitis study on rats, vitamin C intake decreased interleukin-1a and interleukin-1β gene expression by more than twofolds compared to the control

the periodontal pocket depth compared to placebo [64].

and beverages such as tea, coffee, wine, and fruit juices [65].

**1.3 Antioxidant micronutrients**

*1.3.1 Vitamin C*

**Figure 3.**

*matrix metalloproteinase.*

**118**

Research on the relationship between vitamin E and periodontal diseases showed conflicting results. Cohen et al. [79] reported that 5% topical vitamin E gel, in addition to SRP, did not positively affect the formation of plaque and healing of the periodontal tissues. In another study, same researchers showed that vitamin E has a protective role against bone loss [49]. Another study reported that there was no statistically significant difference between the periodontitis patients and the healthy group in terms of serum vitamin E levels [80]. These contradictory results may be related to the study design, the dose of vitamin E, and the investigated different parameters.

In a study on rats, the combination of vitamin E and selenium has been shown to reduce collagen degradation [81]. In addition, vitamin E supplementation has been found to accelerate gingival wound healing [82].

A negative correlation was found between serum α-tocopherol levels and the severity of periodontitis. While the level of α-tocopherol increases, the severity of periodontitis decreases [83]. The use of vitamin E in addition to nonsurgical periodontal treatment has been shown to have positive effects on periodontal parameters [84].

#### *1.3.3 Carotenoids*

Carotenoids are highly potent antioxidants. Linden et al. [85] showed that α-carotene, β-carotene, β-cryptoxanthin, and zeaxanthin levels were significantly lower in patients with moderate to severe periodontitis.

It has been shown that β-cryptoxanthin stimulates bone formation and may stop bone resorption by inhibiting gene expression of osteoclastic enzymes associated with bone resorption [86]. Therefore, it has been suggested that β-cryptoxanthin may reduce the risk of osteoporosis [87]. This may mean that it can slow and/or stop the alveolar bone destruction in periodontal diseases.

Systemic supplementation of 8 mg/day of lycopene was reported to decrease the gingival index in patients with gingivitis [88]. In individuals with chronic periodontitis, it was reported that the supplementation of 4 mg/day of oral lycopene in addition to SRP for 2 weeks resulted in a reduction in clinical attachment loss [89]. Arora et al. [90] found that, in individuals with CP, 8 mg/day of oral lycopene intake for 2 months in addition to SRP had positive effects in plaque index, modified gingival index, probing bleeding, and saliva IL-1β compared to the control group but reported that there was no significant difference in terms of a reduction in pocket depth, clinical attachment, and serum TNF-α levels.

#### *Gingival Disease - A Professional Approach for Treatment and Prevention*

In an animal study, vitamin A deficiency was shown to cause hyperkeratosis in the gingival epithelium, periodontal pocket formation, cement resorption, and osseous changes [91]. In another study, vitamin A deficiency was found to result in thickening of the cement, contraction of the periodontal ligament, irregularities in the periodontal ligament, thickening of the alveolar bone, and labial alveolar periosteum, and these results were shown to be reversible with replacement therapy [92]. In a study analyzing the relationship between the periodontal status and the serum antioxidant levels, it was shown that there was a relationship between the prevalence of increased periodontitis and the low serum levels of β cryptoxanthin and β carotene in men between the age of 60–70 years [85].

#### *1.3.4 Coenzyme Q10*

In periodontal disease, the amount of Coenzyme Q10 decreases in both blood and gingival tissues [93]. Oral intake of Coenzyme Q10 was found to cause an increase in the density of the gingiva and a decrease in the periodontal inflammation and microorganism amounts [94–96]. In another study, coadministration of Coenzyme Q10 and vitamin E orally was found to result in a decrease in plaque index, gingival index, sulcus bleeding index, and pocket depth [97].

#### *1.3.5 Polyphenols*

Polyphenols can increase the antioxidant activity of oral fluids. It has been reported that keeping green tea in the mouth for 2–5 minutes increases the antioxidant capacity of saliva [98], and the consumption of two grapefruits per day for 2 weeks increases the phagocytic capacity of the gingival crevicular fluid neutrophils [99]. Furthermore, *in vitro* studies have shown the antibacterial effect of polyphenols against periodontal pathogens [100].

#### *1.3.6 Flavonoids*

Catechin is an effective antioxidant found in green tea and was found to have protective effects against cancer and cardiovascular diseases. Catechins have also been shown to inhibit the growth of periodontal pathogens and prevent the periodontal tissue destruction [101].

In green tea users, the gingival bleeding index is decreased significantly [102]. Also, it was shown that green tea has an inverse relationship with average pocket depth, levels of bleeding during probing, and clinical attachment level [103]. In another study, it has been reported that green tea inhibits the activity of gingival crevicular fluid collagenase in aggressive periodontitis patients [104]. In an experimental periodontitis model in rats, flavonoids have been shown to prevent inflammatory bone resorption by lipopolysaccharides [105]. Chopra et al. [106] reported that green tea supplement in addition to the nonsurgical periodontal treatment resulted in improvements in the plaque index, gingival index, bleeding during probing, and clinical attachment loss parameters, and the gingival crevicular fluid antioxidant capacity was eight times higher than the control group. In contrast to these studies, in a study conducted in adults, it was found that the consumption of less than one cup of green tea per day was associated with a decrease in the prevalence of periodontal disease, and the consumption of one or more cups of green tea per day resulted in an increase in the prevalence of moderate and severe periodontitis [107].

Cocoa also contains flavonoids, and in an experimental study conducted in rats, a diet rich in cocoa has been shown to reduce periodontal disease-associated oxidative stress and periodontal destruction [108].

**121**

*Antioxidants and Periodontal Diseases DOI: http://dx.doi.org/10.5772/intechopen.81815*

odontal inflammation [114].

levels [118].

gain [120].

regular diet [122].

*1.3.7 Melatonin*

infiltration were reported [121].

be an independent risk factor for periodontal disease.

Coffee, which is a rich source of antioxidants due to its caffeine, caffeic acid, and chlorogenic acid content, has a modulating effect in natural and acquired immune response [109, 110]. In a study on adult males, coffee consumption has been shown to reduce alveolar bone loss [111]. Among periodontitis patients at the periodontal maintenance phase, there was a negative correlation between the coffee consumption [≥1 cup/day] and the prevalence of severe periodontitis [112]. Han et al. [113] suggested that coffee consumption is higher in men with periodontitis, and it may

Quercetin is one of the most common flavonoids in dietary foods. It is a free radical scavenger found in many vegetables, fruits, olive oil, red wine, and tea. It has anti-inflammatory, antiallergic, antiviral, antithrombotic, antimutagenic, antineoplastic, and cytoprotective effects. In an experimental periodontitis study conducted on rats, 75 mg/kg/day oral quercetin administration was reported to decrease lipopolysaccharide-induced osteoclast formation, bone loss, and peri-

Curcumin also has antioxidant properties due to the phenolic compounds in its content. It has antitumor and anti-inflammatory properties [115]. Bakir et al. [116]

The active ingredients of propolis are also flavonoids. In addition, it contains magnesium, calcium, iodine, potassium, sodium, copper, zinc, manganese and iron minerals, and vitamins B1, B2, B6, C, and E. The content that gives most of its antioxidant properties is the caffeic acid, which has phenolic properties. In an experimental periodontitis study performed in rats, it was shown that systemic propolis administration of 100 mg/kg/day for 21 days reduced alveolar bone loss [119]. In addition to SRP, 400 mg of daily propolis supplementation for 6 months was reported to significantly decrease HbA1C levels and pocket depth at 3 and 6 months compared to the control groups and to increase clinical attachment

Proanthocyanidin is a potent antioxidant found in grape seed and red fruits like cranberries, blueberries, etc. In an experimental periodontitis model in rats, 30 mg/kg of proanthocyanidin was given for 30 days, and a decrease in reactive oxygen species in blood and a decrease in histopathologic inflammatory cell

Olive oil contains a large number of polyphenols, a high concentration of α-tocopherols, and low concentrations of carotene and acts as a chain-breaking antioxidant through its oleuropein content. In a 24-month study conducted in rats, it was shown that alveolar bone loss was lower in the group that used olive oil compared to the groups that used sunflower oil and fish oil in addition to their

No significant difference was shown between saliva and plasma melatonin levels of healthy subjects and CP patients; however, melatonin levels were significantly lower in gingival tissues of individuals with CP [123]. It was reported that the levels of saliva melatonin increased after nonsurgical periodontal treatment and salivary

melatonin levels correlated negatively with bleeding during probing [21].

reported that oral curcumin application reduced alveolar bone loss in rats. Kaempferol is one of the flavonoids in vegetables (leek, cucumber, etc.), fruits, and tea. It has an immunomodulatory effect and has been suggested to be used as a host modulator agent in periodontal therapy [117]. In a study on rats, the administration of 10 mg/kg/day of oral kaempferol was reported to decrease the alveolar bone loss, attachment loss, and gingival tissue MMP-1 and MMP-8

#### *Antioxidants and Periodontal Diseases DOI: http://dx.doi.org/10.5772/intechopen.81815*

*Gingival Disease - A Professional Approach for Treatment and Prevention*

and β carotene in men between the age of 60–70 years [85].

index, gingival index, sulcus bleeding index, and pocket depth [97].

polyphenols against periodontal pathogens [100].

*1.3.4 Coenzyme Q10*

*1.3.5 Polyphenols*

*1.3.6 Flavonoids*

odontal tissue destruction [101].

In an animal study, vitamin A deficiency was shown to cause hyperkeratosis in the gingival epithelium, periodontal pocket formation, cement resorption, and osseous changes [91]. In another study, vitamin A deficiency was found to result in thickening of the cement, contraction of the periodontal ligament, irregularities in the periodontal ligament, thickening of the alveolar bone, and labial alveolar periosteum, and these results were shown to be reversible with replacement therapy [92]. In a study analyzing the relationship between the periodontal status and the serum antioxidant levels, it was shown that there was a relationship between the prevalence of increased periodontitis and the low serum levels of β cryptoxanthin

In periodontal disease, the amount of Coenzyme Q10 decreases in both blood and gingival tissues [93]. Oral intake of Coenzyme Q10 was found to cause an increase in the density of the gingiva and a decrease in the periodontal inflammation and microorganism amounts [94–96]. In another study, coadministration of Coenzyme Q10 and vitamin E orally was found to result in a decrease in plaque

Polyphenols can increase the antioxidant activity of oral fluids. It has been reported that keeping green tea in the mouth for 2–5 minutes increases the antioxidant capacity of saliva [98], and the consumption of two grapefruits per day for 2 weeks increases the phagocytic capacity of the gingival crevicular fluid neutrophils [99]. Furthermore, *in vitro* studies have shown the antibacterial effect of

Catechin is an effective antioxidant found in green tea and was found to have protective effects against cancer and cardiovascular diseases. Catechins have also been shown to inhibit the growth of periodontal pathogens and prevent the peri-

In green tea users, the gingival bleeding index is decreased significantly [102]. Also, it was shown that green tea has an inverse relationship with average pocket depth, levels of bleeding during probing, and clinical attachment level [103]. In another study, it has been reported that green tea inhibits the activity of gingival crevicular fluid collagenase in aggressive periodontitis patients [104]. In an experimental periodontitis model in rats, flavonoids have been shown to prevent inflammatory bone resorption by lipopolysaccharides [105]. Chopra et al. [106] reported that green tea supplement in addition to the nonsurgical periodontal treatment resulted in improvements in the plaque index, gingival index, bleeding during probing, and clinical attachment loss parameters, and the gingival crevicular fluid antioxidant capacity was eight times higher than the control group. In contrast to these studies, in a study conducted in adults, it was found that the consumption of less than one cup of green tea per day was associated with a decrease in the prevalence of periodontal disease, and the consumption of one or more cups of green tea per day resulted in an

increase in the prevalence of moderate and severe periodontitis [107].

tive stress and periodontal destruction [108].

Cocoa also contains flavonoids, and in an experimental study conducted in rats, a diet rich in cocoa has been shown to reduce periodontal disease-associated oxida-

**120**

Coffee, which is a rich source of antioxidants due to its caffeine, caffeic acid, and chlorogenic acid content, has a modulating effect in natural and acquired immune response [109, 110]. In a study on adult males, coffee consumption has been shown to reduce alveolar bone loss [111]. Among periodontitis patients at the periodontal maintenance phase, there was a negative correlation between the coffee consumption [≥1 cup/day] and the prevalence of severe periodontitis [112]. Han et al. [113] suggested that coffee consumption is higher in men with periodontitis, and it may be an independent risk factor for periodontal disease.

Quercetin is one of the most common flavonoids in dietary foods. It is a free radical scavenger found in many vegetables, fruits, olive oil, red wine, and tea. It has anti-inflammatory, antiallergic, antiviral, antithrombotic, antimutagenic, antineoplastic, and cytoprotective effects. In an experimental periodontitis study conducted on rats, 75 mg/kg/day oral quercetin administration was reported to decrease lipopolysaccharide-induced osteoclast formation, bone loss, and periodontal inflammation [114].

Curcumin also has antioxidant properties due to the phenolic compounds in its content. It has antitumor and anti-inflammatory properties [115]. Bakir et al. [116] reported that oral curcumin application reduced alveolar bone loss in rats.

Kaempferol is one of the flavonoids in vegetables (leek, cucumber, etc.), fruits, and tea. It has an immunomodulatory effect and has been suggested to be used as a host modulator agent in periodontal therapy [117]. In a study on rats, the administration of 10 mg/kg/day of oral kaempferol was reported to decrease the alveolar bone loss, attachment loss, and gingival tissue MMP-1 and MMP-8 levels [118].

The active ingredients of propolis are also flavonoids. In addition, it contains magnesium, calcium, iodine, potassium, sodium, copper, zinc, manganese and iron minerals, and vitamins B1, B2, B6, C, and E. The content that gives most of its antioxidant properties is the caffeic acid, which has phenolic properties. In an experimental periodontitis study performed in rats, it was shown that systemic propolis administration of 100 mg/kg/day for 21 days reduced alveolar bone loss [119]. In addition to SRP, 400 mg of daily propolis supplementation for 6 months was reported to significantly decrease HbA1C levels and pocket depth at 3 and 6 months compared to the control groups and to increase clinical attachment gain [120].

Proanthocyanidin is a potent antioxidant found in grape seed and red fruits like cranberries, blueberries, etc. In an experimental periodontitis model in rats, 30 mg/kg of proanthocyanidin was given for 30 days, and a decrease in reactive oxygen species in blood and a decrease in histopathologic inflammatory cell infiltration were reported [121].

Olive oil contains a large number of polyphenols, a high concentration of α-tocopherols, and low concentrations of carotene and acts as a chain-breaking antioxidant through its oleuropein content. In a 24-month study conducted in rats, it was shown that alveolar bone loss was lower in the group that used olive oil compared to the groups that used sunflower oil and fish oil in addition to their regular diet [122].

#### *1.3.7 Melatonin*

No significant difference was shown between saliva and plasma melatonin levels of healthy subjects and CP patients; however, melatonin levels were significantly lower in gingival tissues of individuals with CP [123]. It was reported that the levels of saliva melatonin increased after nonsurgical periodontal treatment and salivary melatonin levels correlated negatively with bleeding during probing [21].
