Antibiotics and antimicrobials have long been a mainstay of periodontal disease treatment. However, there is a growing recognition that periodontal disease is caused in large part by oral dysbiosis, and the emergence of increasing numbers of antibiotic-resistant bacterial strains may limit the value of antibiotic treatment for periodontal disease. This has led researchers to investigate the potential of probiotics to restore healthy oral flora. Probiotics are microorganisms that, when delivered as a supplement, displace harmful bacteria and deliver health benefits. Probiotic bacteria that can establish long-term colonies in the oral biofilm may be helpful in preventing and treating periodontal disease (Deepa 2009; Woo 2013; Krayer 2010; Scariya 2015; Sugano 2012; Hajishengallis 2015).
One of the most promising of these bacteria is Streptococcus salivarius (S. salivarius) strain M18. In a clinical study, adults with moderate and severe gingivitis and moderate periodontitis were treated with either probiotic lozenges providing the S. salivarius strain M18 bacteria or no lozenges for 30 days (Scariya 2015). They were examined twice during the treatment period, and 15 and 30 days after the end of treatment. Subjects in the probiotic group were found to have less plaque, better gingival health, and less bleeding on probing than the no-probiotic group; specifically:
- The plaque index score decreased 44% by day 30
- The gingival index score decreased 42% by day 30
- The sulcular bleeding index score decreased 53% by day 30
- The probing pocket depth decreased 20% by day 30
Intriguingly, subjects who received the S. salivarius M18 probiotic lozenges exhibited superior scores on these indices even 30 days after they stopped using the lozenges. This study demonstrated the ability of the probiotic lozenge to significantly improve all four of these commonly used assessments of periodontal health. S. salivarius M18’s ability to colonize the oral cavity contributed to the sustained benefits seen even after the supplementation period ended.
In children, a randomized controlled trial demonstrated supplementation with S. salivarius strain M18 reduced plaque buildup. In addition, salivary bacterial cultures showed children with greater numbers of S. salivarius M18 after treatment also had reduced numbers of cavity-associated S. mutans, which suggests supplementing with this probiotic may prevent cavities (Burton 2013). S. salivarius M18 has also been shown to improve bad breath (halitosis) (Burton 2006).
S. salivarius M18 promotes oral health via several mechanisms. First, it produces enzymes that break down plaque. Next, the probiotic helps maintain healthy oral cavity pH, which is important because imbalanced pH in the mouth can lead to tooth demineralization. Finally, S. salivarius M18 produces powerful antimicrobial compounds called bacteriocin-like inhibitory substances (BLIS) or lantibiotics. These lantibiotics then destroy disease-causing bacteria in the mouth (Burton 2013; Loesche 1996; Heng 2011; Wescombe 2011; Burton 2010).
An article published in Science Advances provides intriguing evidence that Alzheimer’s disease could be caused, in part, by infection with Porphyromonas gingivalis, a keystone pathogen of chronic periodontitis which is a significant risk factor for developing amyloid beta plaques, dementia, and Alzheimer’s.
The scientists studied and compared brain tissue samples from Alzheimer’s disease patients and neurologically normal controls. Interestingly, they found a portion of the “healthy” brains were infected as well, indicating that “…brain infection with P. gingivalis is not a result of poor dental care following the onset of dementia or a consequence of late-stage disease, but is an early event that can explain the pathology found in middle-aged individuals before cognitive decline” (Dominy 2019). These findings suggest better dental care earlier in life may promote brain health later in life.
Xylitol is a small carbohydrate sometimes used in the food industry as a sugarless sweetener. It has been widely studied over the past four decades for its anti-plaque and anti-cavity effects, and has been found to decrease salivary acidity; reduce levels of plaque, harmful bacteria, and gingival inflammation; prevent dry mouth and enamel erosion; and improve salivary flow (Chattopadhyay 2014; NCBI 2015; Nayak 2014). One trial showed xylitol consumption reduced levels of cavity-causing S. mutans bacteria immediately after use, and this effect continued after the subjects stopped using xylitol (Fraga 2010).
Supported by a growing body of evidence demonstrating its beneficial effects, xylitol is now available in therapeutic anti-cavity toothpastes, candies, chewing gums, syrups, and mouthwashes (Lif Holgerson 2006; Nayak 2014; Yuen 2012).
Evidence for a deficiency of coenzyme Q10 (CoQ10) in gum tissue of patients with periodontal disease, and for a beneficial effect of CoQ10 supplementation in these patients, has existed for decades (Iwamoto 1975; Littarru 1971; Nakamura 1974). The mechanisms behind this relationship lie in CoQ10’s important role in controlling inflammation and regulating oxidative stress (Prakash 2010).
A randomized controlled trial of 120 mg of CoQ10 in 30 patients who underwent root planing and scaling found a significant reduction in inflammation of the gums in the CoQ10 group after one and three months compared with placebo (Manthena 2015). In preclinical and clinical studies using topical oral applications of CoQ10 to diseased periodontal tissue, CoQ10 therapy improved periodontal health and inflammation, including as an adjunct to scaling and root planing (Hanioka 1994; Hans 2012; Sale 2014; Yoneda 2013; Chatterjee, Kandwal 2012). An animal study showed CoQ10 moderated the negative effects of omega-6 fatty acids on periodontal-related bone loss (Varela-Lopez 2015).
Fish oil and its omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have shown benefit in a variety of inflammation-related conditions, including cardiovascular disease, diabetes, and autoimmune diseases (Kremer 1995; Calder 2013; Ellulu 2015; Tabbaa 2013). Interestingly, periodontal disease is bidirectionally associated with these conditions (Koutsochristou 2015; Flemmig 1991; Mays 2012; Ogrendik 2013; Patil, Patil, Gururaj 2011; Mayer 2013; Hollan 2013; Altamash 2015). Findings from several studies suggest people with periodontal disease have lower intake of anti-inflammatory omega-3 fats (Iwasaki 2010; Naqvi 2010) and a relatively greater intake of pro-inflammatory omega-6 fatty acids (Iwasaki 2011; Tabbaa 2013). In one study, 80 patients being treated for periodontitis with scaling and root planing were given either 900 mg EPA plus DHA and 81 mg aspirin daily or placebo. After six months, those receiving the omega-3 supplements and aspirin had more improvement in pocket depths and better gingival health (El-Sharkawy 2010).
Lycopene is a red plant pigment found in foods including tomatoes, watermelon, papaya, and pink grapefruit. Lycopene is in the family of plant compounds known as carotenoids and, like other carotenoids, has well-established anti-inflammatory activity (Gupta 2015). A randomized controlled trial in 20 healthy participants with signs of gingivitis found that 8 mg per day of lycopene taken orally was significantly more effective than placebo as an adjunct to regular dental care in the treatment of gingivitis (Chandra 2007). Similarly, another clinical trial in 42 patients with chronic periodontitis already being treated with scaling and root planing found that 8 mg of lycopene per day resulted in greater improvement in indices of periodontal health compared with placebo (Arora 2013). In a randomized trial, patients with both periodontitis and diabetes were treated with scaling and root planing alone or in combination with 8 mg of lycopene per day. Those taking lycopene had greater reductions in periodontal pocket depths as well as improvements in blood glucose control (Reddy 2015).
Vitamin E, particularly gamma-tocopherol, may favorably influence periodontal disease, while in animals, alpha-tocopherol has improved gingival healing, prevented bone loss, and decreased local inflammation. Lower blood vitamin E levels have been associated with more severe periodontal disease (Zong 2015). One study found lower blood and saliva levels of superoxide dismutase (SOD), an important enzyme that quenches oxygen free radicals, in 38 subjects with chronic periodontitis compared to 22 people without periodontal disease. The periodontitis subjects were then treated with scaling and root planing alone or with the addition of 200 mg (300 IU) of vitamin E every other day. After three months the vitamin E group had greater improvements in periodontal health. In addition, SOD levels increased in those receiving vitamin E (Singh 2014).
Curcumin, a polyphenolic phytonutrient from the culinary spice turmeric, is a well-known anti-inflammatory agent (Nagpal 2013). It has also shown anti-microbial activity against bacteria implicated in gingivitis and periodontitis (Shahzad 2015). Several studies have demonstrated that curcumin, applied directly to the gums, demonstrates effectiveness comparable to conventional antimicrobials and is a useful adjunct to scaling and root planing for gingivitis and chronic periodontitis (Muglikar 2013; Behal 2011; Jaswal 2014; Anuradha 2015). In laboratory studies, curcumin has inhibited periodontal disease bacteria and biofilm (Izui 2015; Shahzad 2015).
Rodent studies have shown that supplemental curcumin can reduce periodontal disease-related inflammation in the mouth by inhibiting the expression of inflammatory cytokines and reducing activation of the inflammatory mediator nuclear factor-kappaB in gum tissue, resulting in noticeably lower signs of inflammation (Guimaraes 2012; Guimaraes 2011). These studies used the equivalent of 386 ‒ 1287 mg of curcumin per day for a 175 lb person. In a randomized controlled trial, a highly bioavailable form of curcumin called BCM-95 was found to deliver up to seven times more bioactive curcumin to the blood than previous curcumin preparations (Antony 2008).
Lactoferrin, an iron-binding protein with anti-microbial and immune-modulating properties, is found in saliva and other body fluids (Berlutti 2011). In the mouth, lactoferrin has been shown to help control the growth of colonies of plaque-related bacteria that contribute to both tooth decay and periodontal disease. It inhibits formation of pathogenic biofilm and can help reduce established biofilm. In a clinical study, treatment with a liposomal lactoferrin tablet providing 180 mg lactoferrin daily in five adults with periodontal disease improved periodontal pocket depths after just four weeks (Ishikado 2010). In another clinical study, oral lactoferrin reduced levels of disease-causing bacteria under the gums of chronic periodontitis patients, favorably influencing the biofilm (Wakabayashi 2010). A preclinical study concluded that orally administered lactoferrin may be a powerful treatment and preventive therapy for periodontal inflammation (Kawazoe 2013), while two other laboratory studies demonstrated that lactoferrin can inhibit the growth and biofilm formation of periodontal disease-associated bacteria (Wakabayashi 2009; Dashper 2012).
Periodontal Tissue Support
Calcium and vitamin D. Calcium and vitamin D deficiencies are associated with osteoporosis, periodontal bone loss, and tooth loss, and adequate intakes are necessary for dental and periodontal health (Miley 2009; Garcia 2011; Stewart 2012). In addition to enhancing calcium uptake and metabolism, vitamin D has anti-inflammatory and immune-modulating properties, both critically important for the maintenance of periodontal health (Stein 2014; Dietrich 2005). Vitamin D also helps prevent other chronic inflammatory conditions including cardiovascular disease and diabetes (Stein 2014).
Supplementation with calcium plus vitamin D may be beneficial for people with periodontal disease. In a preliminary study, subjects who took at least 400 IU vitamin D and 1000 mg calcium daily had less severe periodontal disease compared with subjects who did not take these supplements (Miley 2009). These same subjects were followed for one year, and those who took vitamin D and calcium supplements improved more rapidly, with the greatest difference seen after 6 months of treatment (Garcia 2011). Another study in patients being treated for chronic periodontitis found supplementation with 250 IU vitamin D and 500 mg calcium per day for three months led to markedly better measures of periodontal disease compared with no supplemental calcium and vitamin D (Perayil 2015).
A large study that incorporated findings from a food survey, blood tests, and dental exams concluded that low calcium intake results in more severe periodontal disease (Nishida 2000). In another study, women with the highest calcium intake were 47% less likely to have periodontal disease than women with the lowest intake (Tanaka 2014). Similarly, individuals with low vitamin D status have been found to be more likely to have periodontal disease (Antonoglou 2015; Dietrich 2005), and higher vitamin D intake may protect against periodontal disease progression (Alshouibi 2013).
B vitamin complex. B vitamins are necessary for cell growth and metabolism (Kulkarni 2014). A study in 30 subjects with periodontitis, treated with flap surgery, examined the effects of a vitamin B complex supplement. (In flap surgery, severely infected sections of the gum are removed, creating access to deeper tissues and tooth root.) After surgery, participants received either placebo or a supplement providing 50 mg each of B1 (thiamine), B2 (riboflavin), B3 (niacinamide), B5 (pantothenic acid), and B6 (pyridoxine); 50 mcg each of vitamin B12 (cobalamin) and biotin; and 400 mcg of folic acid per day for 30 days. These subjects were then followed up for 180 days. Those treated with vitamin B complex after surgery had more improvement in gingival attachment at the end of the study (Neiva 2005).
Folate. Folate is critical for normal cell division and tissue repair. It has a special role in maintaining periodontal health, and folate deficiency is linked to oral health problems including infections and degeneration and destruction of the gingiva, periodontal ligament, and alveolar bone (George 2013). Individuals with periodontitis have been found to have lower folate levels compared with those without periodontal disease, and a mouthwash with 5 mg folate per 5 mL (1 tsp) has been shown to improve periodontal health in people with periodontal disease (Pack 1984; Yu 2007).
Smoking depletes folate (Vardavas 2008; Gabriel 2006), which may help explain the co-occurrence of smoking and periodontal disease (George 2013). The association between smoking and folate depletion has led some researchers to recommend folate supplementation for smokers with periodontal disease (Erdemir, Bergstrom 2006; George 2013).
Magnesium. Magnesium is necessary for a wide range of cellular functions. Low magnesium intake has been linked to periodontitis (Staudte 2012). In one study, people with the highest magnesium intake had a 36% lower risk of tooth loss compared to people with the lowest intake (Tanaka 2006), and several studies have observed lower levels of magnesium in the blood of individuals with periodontal disease (Meisel 2005; Pushparani 2014). Smoking and diabetes may worsen the magnesium deficit seen in people with periodontitis (Kolte 2012; Pushparani 2014). Individuals with periodontal disease, and particularly smokers (Erdemir, Erdemir 2006), may fare better if they maintain higher blood magnesium levels.
There is also ample evidence that magnesium deficiency is associated with cardiovascular disease, and is commonly seen in people with other chronic inflammatory conditions including metabolic syndrome and diabetes (Nielsen 2014).
Vitamin C. Vitamin C plays a critical role in connective tissue repair processes and regulation of the immune response throughout the body, making it an important factor in the health of the periodontium (Gokhale 2013). In fact, swelling and bleeding of the gingiva is a hallmark of vitamin C deficiency (Ben-Zvi 2012; Alagl 2015; Rubinoff 1989). Vitamin C may also help maintain alveolar bone and help control the balance of oral bacteria (Alagl 2015).
In a randomized controlled trial, 120 participants were divided into four groups of 30. The first group had no periodontal disease, the second had chronic gingivitis, the third had chronic periodontitis, and the fourth had chronic periodontitis and type 2 diabetes. Subjects with periodontal disease were treated with scaling and root planing, half of whom were randomized to receive 450 mg per day chewable vitamin C or placebo for three weeks. Vitamin C administration resulted in significantly greater reductions in gingival bleeding compared with placebo in the chronic gingivitis and the diabetes plus chronic periodontitis groups (Gokhale 2013).
Zinc. Zinc reduces dental plaque and is effective against bad breath. It also has wound healing, immune-supportive, and antibacterial properties that can all contribute to periodontal health (Kulkarni 2014). In one study, zinc deficiency was associated with an increased number of cavities and poorer gingival health in children (Atasoy 2012). Low zinc levels have also been noted in people with both diabetes and periodontitis (Pushparani 2014).
Green tea. Green tea leaves are a rich source of polyphenols called catechins, which are well known for their ability to reduce oxidative stress and inflammation (Nugala 2012; Babu 2008). Epigallocatechin gallate (EGCG) is the most abundant and most studied of green tea’s catechins (Hamilton-Miller 2001; Anita 2014; Wolfram 2007). Researchers have found that green tea catechins have antibacterial activity against cavity-causing bacteria such as S. mutans and bacteria implicated in periodontal disease such as Porphyromonas gingivalis (Hirasawa 2002). Green tea catechins may also promote oral health by preventing plaque formation (Hamilton-Miller 2001), inhibiting enzymes involved in tissue breakdown (Chatterjee, Saluja 2012; Nugala 2012), and preventing alveolar bone loss (Chatterjee, Saluja 2012; Nugala 2012).
A survey in Japanese men found that green tea intake was associated with better oral health. For each cup of tea consumed per day, there was a measurable benefit observed in the form of decreased average pocket depth, improved gingival attachment, and reduced gingival bleeding (Kushiyama 2009). Drinking green tea has been recommended as a strategy for maintaining periodontal health in patients with periodontitis (Ramasamy 2015).
Green tea catechin extracts have been used as an ingredient in mouthwash or applied directly to tissues with periodontal disease. This method has demonstrated efficacy comparable to conventional antimicrobial mouthwash in reducing plaque, and can enhance the effectiveness of scaling and root planing to treat chronic periodontitis (Kaur, Jain 2014; Kudva 2011; Hattarki 2013; Chava 2013).
Pomegranate. Pomegranates are high in a wide array of beneficial polyphenol phytonutrients demonstrated to prevent cancer, cardiovascular disease, diabetes and other conditions. Pomegranate polyphenols are potent defenders against oxidative stress and inflammation (Basu 2013; Prasad 2014; Jurenka 2008). A mouthwash that contained pomegranate extract, added to scaling and root planing, performed comparably to a conventional antimicrobial chemical, and other localized applications of pomegranate have shown benefit in treatment of periodontal disease (Batista 2014; Sastravaha 2005; DiSilvestro 2009).
Essential oils. Essential oils are aromatic plant extracts rich in compounds called monoterpenes. Mouthwashes and toothpastes with essential oils and monoterpenes from plants such as peppermint and clove have long been in use, and scientists now recognize that the antimicrobial effects of these compounds may explain much of their benefit for oral health (Zomorodian 2015; Allaker 2009). For example, Listerine mouthwashes contain three monoterpenes: menthol, thymol, and eucalyptol (Allaker 2009). Numerous studies have shown that Listerine use is associated with decreased levels of harmful oral bacteria, plaque, and gingival inflammation (Goutham 2013; Charles 2014; Cortelli 2013; Cosyn 2013). A randomized controlled trial in chronic periodontitis patients found that an essential oil mouthwash significantly reduced populations of two types of pathogenic bacteria, and concluded that an essential oil rinse may be an effective adjunct to standard treatment for reducing bacterial counts in gum pockets (Morozumi 2013).
A study involving a mouthwash made with the essential oil from the Ayurvedic herb Ocimum sanctum, also known as holy basil or tulsi (Cohen 2014), found positive periodontal effects (Gupta 2014). In another study, 49 participants with gingivitis were treated with topical 2.5% tea tree oil gel, 0.2% chlorhexidine gel, or placebo gel applied with a toothbrush twice daily for eight weeks. The major monoterpenes in tea tree oil are cineole and terpineol. The greatest improvements in gingival health were seen in the tea tree oil group (Soukoulis 2004).
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