International Journal of Cosmetic Science, 2010, 19

doi: 10.1111/j.1468-2494.2010.00585.x

Review Article

Oral malodour and active ingredients for treatment

N. Lourith and M. Kanlayavattanakul
School of Cosmetic Science, Mae Fah Luang University, Chiangrai, Thailand

Received 18 July 2009, Accepted 14 December 2009

Keywords: bad breath, halitosis, oral malodour, treatment

Synopsis Oral care preparations are widely used for the treatment of oral malodour as over-the-counter products. Bad breath is highly distressing to an individuals condence during social interaction, which is a large concern nowadays as the consumption of these products is increasing worldwide. However, oral deodorant ingredients are rarely studied compared with other cosmetic ingredients, and the only preparations which are well known are those contained in dentifrices and mouthrinses. This review briey summarizes the compounds which cause oral malodour and the treatments available. The active ingredients in various preparations are emphasized and novel products are presented. Resume Mauvaise haleine et ingredients actifs pour son traitement Des preparations de soins buccodentaires sont largement utilisees en vente libre pour le traitement de lhaleine. La mauvaise haleine intervient fortement dans la conance dun individu au cours dechanges sociaux. De nos jours, cette grande preoccupation se traduit par laugmentation de la consommation de ces produits dans le monde entier. Cependant, les ingredients de ces deodor ants buccaux sont rarement etudies face aux autres ingredients cosmetiques et les seules prepaCorrespondence: Nattaya Lourith, School of Cosmetic Science, Mae Fah Luang University, Chiangrai 57100, Thailand. Tel.: +66 53 916834; fax: +66 53 916831; e-mail: nattayal@mfu.ac.th

rations bien connues sont celles contenues dans les dentifrices et les bains de bouche. Cette revue ` ` recapitule brievement les composes a lorigine de la mauvaise haleine et les traitements disponibles. Les principes actifs dans diverses preparations sont examines et de nouveaux produits sont presentes. Introduction Bad breath or oral malodour is recognized as a signicant problem during socialization with high concern throughout the world as evidenced by the increasing consumption of mouthrinses [1], which are used to limit the psychological impact of decreased condence and distress during social interaction. Subsequent depression decreases motivation to improve oral hygiene and vice versa [2]. There are several factors which lead to oral malodour or halitosis. These include microorganisms which cause odorous degradation substances derived from food and drugs, oral hygiene behaviour and respiratory conditions as previously described [3]. The oral cavity is obviously the prevalent cause [4] as it has a suitable environment for the numerous bacteria which colonize the mouth to induce odour [5]. The treatment of halitosis can include a combination of mechanical [68] and chemical strategies [9] to neutralize or suppress vomit odour, and rinsing in addition to gargling with an efcacious mouthwash is advised [10]. Gargling of the mouthrinse towards the throat is recommended [11]. This review focuses on oral care ingredients, which are broadly used as safe and effective oral deodorants [12] and bought as over-the-counter products [4, 13, 14] in an attempt to achieve an

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N. Lourith and M. Kanlayavattanakul

understanding of this neglected area of personal care [4, 15]. Scientic literatures provided by the ScienceDirect, WileyBlackwell and American Chemical Society publications and patents were searched on bad breath, halitosis and oral malodour. The causes of oral malodour were addressed and the active ingredients for treatment were summarized. Although the active ingredients in oral care preparations such as dentifrices, mouthrinses and fresheners [16] are reviewed, other products for the relief of bad breath are also presented. Odorous compounds and their generation Oral malodour is produced by volatile sulphur compounds (VSCs) following the degradation of amino acids containing sulphur such as cysteine, cytine and methionine [17, 18] by oral anaerobes including Treponema denticola, Porphyromonas gingivalis, Prevotella intermedia, Bacteroides forsythus, Fusobacterium nucleatum, Porphyromonas endodontalis and Tannerella forsythensis [1923] and tongue coating bacteria such as Veillonella, Actinomyces and Prevotella species [24]. Volatile sulphur compounds produced by protein decomposition are mainly hydrogen sulphide (H2S) and methyl mercaptan (CH3SH) [2527] causing bad breath odor with the odorous nitrogen compounds, cadaverine [28], putrescine [29], indole and amines [30, 31]. Fatty acids such as acetic acid, propionic acid, butyric acid and isovaleric acid also contribute to exhaled vomitous bad breath [32]. Other compounds produced during physical illness which accumulate in bad breath are ketonic compounds, acetone and methylethylketone in addition to n-propanol, the heterocyclic compounds, aniline and o-toluidine and the nitrogen compounds, dimethylamine and trimethylamine (CH3N) [4]. Thus, several volatile organic compounds (VOCs) accumulate in bad breath. The detection threshold (mol dm)3) of these odorous compounds are as follows; CH3SH (1.0 10)11) < CH3N = isovalerate (1.8 10)11) < butyrate (2.3 10)10) < H2S (6.4 10)10) < putrescine (9.1 10)10) < dimethyl disulphide (CH3SSCH3) (5.9 10)8) [33]. However, H2S and CH3SH are mainly used for oral malodour diagnosis [3337]. The generation of vomit odour by periodontal bacteria has been supercially studied and has been revealed to be enzyme regulated, particularly the bacterial degradation of methionine. Methyl mer-

captan is produced from methionine by enzymatic degradation regulated by methionine-a-deaminoc-mercaptomethane-lyase (METase). This enzyme catalyses a- and c-elimination producing a-ketobutyrate, CH3SH and ammonia [3841]. Cadaverine is produced following the degradation of lysine by the enzyme lysine decarboxylase [4244]. Hydrocarbons and fatty acids are signicantly induced by oxidative stress [45], of which reactive oxygen species oxidize DNA, proteins, carbohydrates and lipids [46], including fatty acids that consequently generate volatile aldehydes and alkanes [47]. In association with the previously mentioned causes, anxiety also contributes to bad breath [48]. In addition to the factors mentioned above, salivary ow rate [49] and salivary protein content [50] also inuence oral malodour. Active ingredients for oral malodour management For bad breath reduction, ingredients which have an inhibitory effect on sulphide-reducing bacteria in the oral cavity can be used with other compounds which are capable of neutralizing vomit odours as the sulphur reducing bacteria are not the only contributors to oral malodours [51]. The active ingredients used are summarized as follows: Botanical extracts The volatility of methyl mercaptan can be reduced by betel leaves (Piper betel) which are used to treat halitosis [52, 53]. The antimicrobial phenolic compound in betel leaves was identied as allylpyrocatechol [53]. Other phenolic compounds which inhibit oral microbes and reduce bad breath are catechin and resveratrol extracted from licorice (Glycyrrhiza spp.), Camellia spp., Acacia catechu, Polygonum spp., Areca catechu, Potentilla fragarioides, Rheum, Prunus, Ginkgo biloba, Machilus, Elaeagnus, Apocynum and Geranium [54], including phytic acid [55]. In addition, a herbal formulation of Echinacea angustifolia, Pestacia lentiscus, lavender (Lavendula angustifolia) and sage (Salvia ofcinalis) extracts was found to be effective against oral malodour [56]. In addition to antimicrobial efcacies in these plant extracts, their aromatic effects are appreciable for bad breath neutralization and avouring the treatment products as well.

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Cetylpyridinium chloride This antimicrobial agent [57, 58] reduces VSCs [59] and has been included in several preparations [60] such as mouthrinses [58], mouthspray [61] and dentifrices [62], its stability is enhanced by papain [63]. Cetylpyridinium cations were also used [55, 64] in an oral gel [65]. The oral care preparations containing cetylpyridinium chloride are not limited to humans but can also be used in animals [66]. Thus, this active ingredient becomes the most commonly used for bad breath overwhelming in various preparations. Chlorhexidine Chlorhexidine reduces offensive oral odour [67, 68] by reducing VSCs in the breath [69, 70] and produces long-term reduction [71] because of its antimicrobial efcacy [72] of which the commonly used preparations are mouthrinses. The concentration of chlorhexidine in mouthrinses is 0.12%, which is efcacious with no unpleasant taste and no staining effect on teeth [73, 74]. Chlorine dioxide The stable free radical, chlorine dioxide, has been used in mouthwashes for the reduction of VSCs and VOCs [75] as it is an oxidizing agent of cysteine and methionine, both precursors of VSCs [76]. In addition, chlorine dioxide has antimicrobial efcacy, thus prevents dental diseases and consequently reduces putrefaction [77]. Mouthrinses containing 1.0% NaClO2 which generates ClO2 were found to be sufcient to reduce VSCs for at least 8 h [78, 79]. Dentifrices containing this oral antimicrobial have also been formulated [80] and include various preparations such as mouthspray [81, 82] and chewing gum [83]. In addition, it was used together with zinc ions to limit offensive breath by complexing with sulphur [84]. However, the adverse effects resulting from generated chlorite ions remain unclear [85] that doubted its safety. Dehydroascorbic acid This ascorbic acid derivative was found to prolong the suppression of oral malodour for 3 h because of its oxidizing effect [86]. However, preparations incorporating this active ingredient are rare
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because of the instability of this vitamin C derivative. Essential oils With bactericidal activity against dental pathogenic microorganisms which accumulate in oral malodour, essential oils have been included in mouthwashes [87], particularly mint oils which inhibit pathogens in the respiratory tract [88], essential oils also have benecial organoleptic properties. Oral care preparations containing essential oils were found to be effective against oral malodour [89] with comparative activity to chlorhexidine [90]. Essential oils of anise, fennel, basil and juniper berry in mouthwash, toothpaste and mouthspray preparations were used to neutralize garlic odour in breath [91]. A combination of the aroma compounds, thymol, eucalyptol, menthol and methyl salicylate from essential oils were formulated at acidic pH (3.05.5) and afforded antiseptic and anticaries activities in dentifrices [92]. In addition, spearmint, peppermint and eucalyptus oils were widely used for their therapeutic and psychological effects, tea tree oil was used to suppress oral malodour with methyl acetate and methyl lactate as antibacterial enhancers [93]. Furthermore, bay, bergamot, caraway, cedar, cinnamon, citronella, clove, coriander, laurel, lavender, lemon, marjoram, mustard, orange, orris, parley, pimento, pine, rosemary, sage, sassafras, terpentine, thyme and witch hazel oils were used in several dosage forms to reduce oral malodour [61, 94, 95]. Mouthrinses are the major preparations for bad breath treatment and most contain alcohol. However, it is possible for these alcohols to be metabolized into odorous compounds thus elevating malodour. Therefore, concentrations of ethyl alcohol in mouthrinses tend to be reduced [11]. Aroma compounds in essential oils have also been used in innovative products as complex compounds of menthol and anethole with b-cyclodextrin in lipsticks for breath refreshing [96]. Hydrogen peroxide A reduction in VSCs was found following treatment with H2O2 alone [97] and in combination with NaHCO3 [98].

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Sodium bicarbonate The use of baking soda, the common name for NaHCO3, in halitosis treatment was carried out either in combination with peroxide [98] or triclosan [99] and was found to be highly effective at high concentrations [100]. Triclosan The antibacterial triclosan or 2,4,4-trichloro-2hydroxydiphenylether [101] is widely incorporated into oral care products particularly for halitosis treatment as it is highly compatible with other ingredients [102] and is stable [103] in various preparations [99, 101]. Triclosan at a concentration of 0.3% reduced VSCs [104], and the calcium-based system was claimed to enhance this activity [101]. Therefore, triclosan was incorporated in a combination formula with several active ingredients for the suppression of oral malodour [105109]. Zinc salts Zinc salts have been widely used in the control of oral malodour as they are non-toxic and do not stain teeth compared with other metal salts. These metal salts suppress the production of VSCs in the

following order: HgCl2 = CuCl2 = CdCl2 > ZnCl2 > SnF2 > SnCl2 > PbCl2 [110]. ZnCl2 is mainly used in mouthrinses as an effective oral deodorant [111] and in dentifrices [112], and its activity is concentration dependent [79]. However, its unpleasant taste alters the incorporated concentration and 0.1% has been found to be acceptable. Despite its unpleasant taste, masking by other ingredients can overcome this problem in order to sustain its efcacy [74]. In addition to zinc chloride, zinc lactate was also used to treat offensive breath with higher efciency than chlorhexidine (0.20%) and at a lower concentration (0.14%) [113]. Zinc acetate [58], zinc citrate [65] and zinc nitrate were also used [114]. Zinc salts have been used alone and in combination with other ingredients such as, chlorhexidine and cetylpyridinium chloride [58, 115, 116] with a signicant reduction in vomit odour producing anaerobes [117] and in combination with NaHCO3 in toothpaste [118] and with NaClO2 generating ClO2 in mouthrinses [79] and dentifrices [114]. The use of zinc for breath odour neutralization is not limited to mouthrinses and dentifrices but has also been included in a chewing gum [119]. In addition to the above ingredients, activated carbon is used as an oral malodour absorbent in several preparations [120] as well as tropolone compounds [94, 121].

Table I Active ingredients for oral malodour treatment in each preparation

Ingredients Functions Preparations

Botanical extracts Cetylpyridinium chloride Chlohexidine Chlorine dioxide

Antimicrobial [5255] Antimicrobial [5759] Antimicrobial [72] Cysteine and methionine oxidizing agent [76], antimicrobial [77] Amino acid containing sulphur oxidizing agent [86] Antimicrobial [88], antiseptic and anticaries [92] VSCs reduction [97] VSCs reduction [98100] Antimicrobial [101] Antimicrobial [110, 116, 117] Odorant absorber [120] Tongue coating bacterial reduction

Tablet [56] Mouthrinse [58], mouthspray [61], dentifrice [62], oral gel [55, 64, 65] Mouthrinse [73, 74] Mouthwash [75], dentifrice [80], mouthspray [81, 82], chewing gum [83] Dentifrice [86] Mouthwash [87, 91], mouthspray [91], dentifrice [91, 92], lipstick [96] Dentifrice [97] Mouthrinse [99], dentifrice [100] Dentifrice [101109] Mouthrinse [65, 79, 113, 117], dentifrice [112, 113, 116], chewing gum [117] Dentifrince, chewing gum, scraper [120] Oral biolm [122, 123], dentifrice [105]

Dehydroascorbic acid Essential oils Hydrogen peroxide Sodium bicarbonate Triclosan Zinc salts Activated carbon Enzyme

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Furthermore, there are currently several new preparations containing enzymes claimed to freshen breath. An oral biolm from a protease enzyme, papain and hydroxyalkyl cellulose was developed [122, 123] as well as a dentifrice containing papain, a lipase enzyme (glycoamylase) and triclosan [105]. In addition, stannous salts have also been used as active ingredients with minimal side effects such as tooth staining and astringency [124] as well as alkali metal chlorides [110, 125]. Conclusions Oral malodour reduces an individuals condence during social interaction and several treatments have been developed to regain condence and socialization. Mechanical treatments such as tongue scraping or teeth brushing with oral preparations are recommended for oral malodour [69]. Active ingredients in oral care preparations play an important role in neutralizing or suppressing vomit odour and mainly rely on their antimicrobial efcacy towards oral cavity microbes. However, some of these compounds, such as essential oils and botanical extracts, contribute to avouring the preparations and are more benecial than other ingredients as they do not have staining effect on teeth and are believed to be safer than synthetic agents. Furthermore, a combination of active ingredients enhances oral deodorant activity and stability as well as having an anticaries effect. In addition to the incorporation of multifunctional ingredients into mouthrinses and dentifrices, other preparations have also been introduced (Table I). Breath refreshing lipsticks [96] and biolms [122, 123] have been developed for more convenient use in order to regain the individuals condence and to stop oral malodour. Acknowledgements The authors acknowledge Kagawa University on library and data base accesses and Mae Fah Luang University on facility support for this manuscript preparation. References
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