The Effects of Flavonoids on Oral Health

Many plant products, such as fruits, grains, tea, wine, barks, and roots, possess bioactive ingredients known as flavonoids—a class of polyphenol organic compounds that is part of a larger group of plant-based phytochemicals.¹ In recent years, flavonoids have garnered attention in dentistry and other sciences because they have shown potential health benefits, including antiviral and antibacterial activities.² Specifically, they may alter the structural integrity of bacterial cell membranes, inhibit peptidoglycan synthesis in cell walls, and prevent biofilm formation.³ For example, dental plaques are formed by cariogenic microorganisms that reside in a biofilm in a susceptible host. Streptococcus species account for a large portion of these, and in some cases, Staphylococcus, Actinomycetes, Lactobacillus, and Enterococcus may also be found in the oral cavity. These bacteria may also interact with other microorganisms present in the oral cavity, such as Candida albicans, which can cause oral thrush.^4,5 Many of these microorganisms perform beneficial functions, including the conversion of dietary nitrates into nitrites that are further converted to nitric acid and serve as vasodilators and inhibitors of cariogenic bacteria.⁶ However, the disruption of microbial homeostasis due to diet or merely immune response triggers the onset of diseases such as dental caries.⁴ Thus, foods or products that provide flavonoids may be beneficial in promoting oral and overall health.

A growing interest in plant-based products has drawn increased attention to flavonoids beyond dietary sources and has led consumers to consider toothpastes and mouthrinses made with alternative ingredients, including herbs and spices that contain polyphenols.⁷ Concerns surrounding possible side effects or sensitivities associated with traditional oral care products and an increase in antibiotic-resistant strains of many bacteria have also drawn attention to the bacteriostatic effects of herbal medicines and their possible benefits in the oral cavity.^8–10

Furthermore, overall growth in the oral care industry and in at-home oral care remedies has, in part, been fuelled by the COVID-19 pandemic, which led more patients to choose at-home oral care remedies to decrease exposure to COVID-19. This trend is predicted to persist, suggesting that flavonoids and other natural ingredients may play a continued role in dental hygiene, both through dietary sources that impact oral health and through oral care products that patients choose.¹¹

Toothpaste and Mouthrinse

The antimicrobial activity of flavonoids has been explored in numerous studies and in real-world applications. One study by Forouzanfar et al¹² examined the performance of saffron, a spice with antioxidant properties that contains flavonoids,¹³ against a placebo among patients experiencing marginal gingivitis. Participants were assigned to use either the saffron toothpaste or an unspecified placebo, and pocket depth, gingival index, plaque index, and bleeding on probing were examined before and after 1 month of using either the saffron extract toothpaste or placebo. The group that used the saffron toothpaste experienced significant improvement in reducing gingival indices and bleeding on probing in comparison with the placebo group. No further details about the study methodology were provided, limiting comparisons with other research.

In vitro tests studied the effects of toothpastes made from the medicinal plants Syzygium aromaticum (clove), Dennettia tripetala (pepper fruit), and Jatropha curcas (physic nut), which all contain phenols, flavonoids, alkaloid, and saponins, on oral pathogenic microorganisms such as Escherichia coli, Bacillus subtilis, S. aureus, S. epidermidis, Micrococcus luteus, Streptococcus mutans, S. pyogenes, L. acidophilus, and C. albicans. The plant-based toothpastes inhibited bacterial growth, particularly when more than one plant was included (eg, clove combined with pepper fruit and/or physic nut), possibly due to synergistic effects of their bioactive compounds. The authors concluded that these biomolecules may be safe and effective toothpaste ingredients.¹⁴ Similarly, a study by Uju et al¹⁵ conducted in Nigeria showed that clove, tobacco, and bitter kola all have inhibitive effects on S. mutans, with the most effective being clove extract. The authors suggest that clove extract be considered for use in toothpaste production. Despite the flavonoids provided by tobacco, its use can have adverse effects on oral health. Thus, efforts have been made to eliminate tobacco and nicotine from toothpastes and powders.¹⁶ 

Faria et al¹⁷ compared mouthrinses produced with extracts from the flavonoid-containing plants Calendula officinalis (pot marigold) and Camellia sinensis (tea plant) against a traditional oral rinse containing chlorhexidine gluconate. The plant-based mouthrinses demonstrated some bacteriostatic effects against microbes that had attached to sutures after molar extraction, but their performance did not exceed that of chlorhexidine. However, while chlorhexidine has been shown to impair cell proliferation needed for wound repair, extracts of both green tea and pot marigold flowers have demonstrated the ability to enhance healing.¹⁷ Additionally, a recent review of flavonoids showed they are also effective in preventing and reducing the severity of periodontitis when delivered to patients through mouthrinses, toothpastes, and food products.¹⁸ They may reduce inflammation and periodontitis by targeting immune signalling that occurs in response to plaque-bacterial biofilm formation.

Endodontic and Post-Surgical Uses

After oral surgeries, bacteria in plaque may gain access to circulating blood, increasing the risk of septic inflammation of the endocardium.^19,20 In an in vitro experiment using cardiomyocyte cells, the flavonoid myricetin inhibited inflammatory responses and cell signalling pathways that result from exposure to peptidoglycan, a cell wall component of dental plaque bacteria.¹⁹  The authors concluded that future research should examine the use of myricetin for treating periodontal diseases and infective endocarditis. Similarly, licorice, when used alone or in root canal medications, exhibited a significantly greater bactericidal effect against E. faecalis, a bacterium associated with oral infections, inhibiting its growth compared to the traditional medication, calcium hydroxide.²¹ The mechanisms behind the bactericidal effects of flavonoids include plasma membrane disruption, inhibition of bacterial toxins, peptidoglycan, adenosine triphosphate, electron transport chain, or nucleic acid synthesis.²²

In endodontics, natural herbal products, such as licorice ethanolic extracts, have been used in root canal therapy for cleaning and disinfecting because they have exhibited antibacterial properties against several oral pathogenic microbes. Baicalein, a flavonoid found in the root of the Scutellaria baicalensis plant, promotes remineralization and alkaline phosphatase activity, angiogenic factors, and morphogenetic protein of human dental pulp cells. Other uses of natural products (grapefruit, tangerine, lime, and lemon oils) in root canal therapy include serving as solvents for softening of gutta-percha and maintaining the viability of human periodontal ligament cells when used as a storage medium for avulsed teeth (for example, aloe vera).²³

Additionally, a study by Soltani et al⁹ demonstrated that green tea, another flavonoid-rich plant, was very effective in reducing gingival bleeding following oral surgery. After mandibular molar extractions, researchers either used a sterile gauze or a sterile gauze permeated with green tea to reduce gingival bleeding. Gingival bleeding took twice as long to stop among subjects in the control group compared to the group treated with green tea gauze.

Use of Propolis as a Medicament

The ability of propolis to limit dental plaque accumulation has contributed to its use as an ingredient in mouth­rinses and toothpastes. Propolis is a naturally occurring resinous substance obtained by bees mixing beeswax with substances from different plant species.²⁴ Flavonoids are major phytochemicals in propolis, although other phenolic compounds are also present.²⁵

Both Brazilian green and red propolis are effective at treating oral diseases.²⁶ Propolis may reduce gingival inflammation.^24,25 Propolis can be used as a canal irrigation ­solution or intracanal medicament in endodontic treatments. As a storage medium, it has the potential to keep periodontal ligament cells viable for 6 hours or longer, and may be more effective than traditional products (milk, balanced salt solution or serum). However, it may be more difficult to obtain propolis and prepare a solution, so milk may be preferred. Propolis is also capable of inhibiting osteoclast activity, inducing the production of tubular dentin, and decreasing pulpal inflammation.²⁶

During the treatment of malocclusions with narrowed maxilla in orthodontics, bone remodelling takes place within the palatine suture.²⁷  Research with rats found that systemic delivery of a propolis solution  increased bone remodelling within the palatine suture and increased the number of osteoblasts.²⁴ When constructing restorative dentin, propolis can be used to reduce the permeability of the dentin and provides advantages over calcium hydroxide in direct pulp capping.^23,24  It also aids in the healing of surgical wounds and is used in socket wounds after teeth extraction to foster quick epithelial repair.^24,26,28

Additional Applications

The use of flavonoids in other branches of dentistry has also been studied. An experiment by Yang et al²⁹ showed that epigallocatechin-3-gallate—a type of catechin in green tea—when used with ethanol-wet bonding promoted stronger bonding strength and stability of etch-and-rinse adhesives on dentin. This result  suggests that further study is warranted to assess feasibility of widespread clinical use.

Numerous flavonoids (proanthocyanidin, naringin, and quercetin) have demonstrated efficacy in remineralizing root caries lesions.³⁰ In demineralized dentin, these flavonoids increased the modulus of elasticity and tensile strength, with proanthocyanidin working best likely due to its ability to improve the cross-linking ability of the dentin collagen matrix.²⁷ Further study to explore practical uses in clinical settings is warranted.

Dietary Intake

Though controlled studies on the effects of specific flavonoid-rich foods and their effect on oral health are limited, results to date have supported flavonoids, perhaps due to their antioxidant, anti-inflammatory, anti-adhesive and antibacterial properties.¹⁸ For example, Loon et al⁸ concluded that bromelain extract from pineapples suppressed the growth of S. aureus, perhaps due to the presence of flavonoids, bromelain, and vitamin C.

Due to their anti-adhesive properties, cranberries may also prevent dental caries by inhibiting biofilm formation. Research with cranberry juice found that it interfered with adhesion of Streptococcus bacteria in biofilms, possibly through interactions between cranberry components and hydrophobic proteins on the outside of bacteria cells.³¹

Tea is another rich source of flavonoids that may promote oral health due to its antibacterial effects.³² Given the presence of flavonoids in tea, Kawarai et al³³ compared the difference in effect of Assam tea and green tea against S. mutans. Assam tea showed stronger biofilm inhibition activity against S. mutans than green tea. This may have be due to the presence of galloylated catechins at high concentrations in Assam tea, coupled with smaller amount of polysaccharides, which, together, may work to inhibit biofilm formation.

Dietary Recommendations for Flavonoids

Huang et al³⁴ analyzed the 2013-2016 National Health and Nutrition Examination Survey data with the Phenol Explorer Database to estimate the amount of polyphenols consumed by American adults. After phenolic acids, flavonoids were consumed the most (379.1 ± 10.7 mg/day). Flavan-3-ols were the most consumed flavonoid subclass reported in this study with a mean intake of 223.2 ± 7.8 mg/day. Surveys of flavonoid intake in the United States have reported tea, wine, beer, citrus fruits, and apples as important sources of flavonoids among adults.^34,35

Research on the intake of specific flavonoid-rich foods and the role in oral health is limited but promising. For example, the antibacterial benefits of bromelain extract from pineapple⁸ may also be present when the fruit is included in the diet. Indeed, research with school-aged children found a decreased incidence of viral and bacterial infections and improved granulocyte counts in those who consumed one serving to two servings of pineapple daily.³⁶

Further research is also needed to clarify the mechanisms that may make cranberries an inhibitor of biofilm formation and to understand the necessary serving size of cranberry juice to provide benefits.  Given that the current dietary guidelines recommend consumption of two servings of fruit daily for a 2,000 calorie diet,³⁷ canned pineapple and cranberry juices could be included as part of a healthy diet that may provide additional oral health benefits.

Dental hygienists and other health professionals could contribute to increasing flavonoid consumption by educating patients about the enormous benefits that fruits, vegetables, and other flavonoid-rich foods provide (Table 1, page 35). Given the growing interest in natural oral care products, many of which contain flavonoids, oral health professionals can also discuss these options with patients as additional research about their effectiveness becomes available.

Conclusions

Although emerging evidence suggests that flavonoids may provide oral health benefits, more research is needed to understand how other types of plant chemicals contribute to the effectiveness of flavonoids and the potential benefits of natural oral care products. Future work should also evaluate the possibility of supplement-drug interactions.^38,39 As research in these areas continues and understanding of the potential benefits and uses of flavonoid-rich foods and products grows,⁴⁰ oral health professionals will be better able to target guidance for patients seeking natural alternatives for oral care as well as nutrient-rich foods.

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From Dimensions of Dental Hygiene. August 2022; 20(8)34-37.