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Review Article Oral malodour and active ingredients for treatme

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Review Article: Oral malodour and active
ingredients for treatment
N. Lourith
M. Kanlayavattanakul
First published: 21 June 2010
https://doi.org/10.1111/j.1468-2494.2010.00585.x
Cited by: 5
Nattaya Lourith, School of Cosmetic Science, Mae Fah Luang University, Chiangrai 57100,
Thailand. Tel.: +66 53 916834; fax: +66 53 916831; e‐mail: [email protected]
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Synopsis
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Oral care preparations are widely used for the treatment of oral malodour as over-the-counter
products. Bad breath is highly distressing to an individual’s confidence 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 briefly summarizes the compounds
which cause oral malodour and the treatments available. The active ingredients in various
preparations are emphasized and novel products are presented.
Introduction
Bad breath or oral malodour is recognized as a significant 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 confidence 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 [6-8] and chemical strategies [9] to neutralize or
suppress vomit odour, and rinsing in addition to gargling with an efficacious
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 understanding of this neglected area of personal care
[4, 15]. Scientific 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 [19-23] 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) [25-27] 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 [33-37].
The generation of vomit odour by periodontal bacteria has been superficially
studied and has been revealed to be enzyme regulated, particularly the bacterial
degradation of methionine. Methyl mercaptan is produced from methionine by
enzymatic degradation regulated by methionine-α-deamino-γ-mercaptomethanelyase (METase). This enzyme catalyses α- and γ-elimination producing αketobutyrate, CH3SH and ammonia [38-41]. Cadaverine is produced following the
degradation of lysine by the enzyme lysine decarboxylase [42-44].
Hydrocarbons and fatty acids are significantly 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 flow rate [49] and salivary
protein content [50] also influence oral malodour.
Active ingredients for oral malodour
management
For bad breath reduction, ingredients which have an inhibitory effect on sulphidereducing 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 identified 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 officinalis) extracts was found to
be effective against oral malodour [56]. In addition to antimicrobial efficacies in
these plant extracts, their aromatic effects are appreciable for bad breath
neutralization and flavouring the treatment products as well.
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
efficacy [72] of which the commonly used preparations are mouthrinses. The
concentration of chlorhexidine in mouthrinses is 0.12%, which is efficacious 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 efficacy, thus prevents dental diseases and consequently reduces
putrefaction [77]. Mouthrinses containing 1.0% NaClO2which generates ClO2 were
found to be sufficient 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 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 beneficial 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 (3.0–5.5) 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 β-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].
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-2′-hydroxydiphenylether [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 [105-109].
Zinc salts
Zinc salts have been widely used in the control of oral malodour as they are nontoxic 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 efficacy [74]. In addition to zinc chloride, zinc lactate was also
used to treat offensive breath with higher efficiency 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 significant
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].
Furthermore, there are currently several new preparations containing enzymes
claimed to freshen breath. An oral biofilm 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 individual’s confidence during social interaction and
several treatments have been developed to regain confidence and socialization.
Mechanical treatments such as tongue scraping or teeth brushing with oral
preparations are recommended for oral malodour [6-9]. Active ingredients in oral
care preparations play an important role in neutralizing or suppressing vomit
odour and mainly rely on their antimicrobial efficacy towards oral cavity microbes.
However, some of these compounds, such as essential oils and botanical extracts,
contribute to flavouring the preparations and are more beneficial 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 biofilms [122, 123] have been developed for more
convenient use in order to regain the individual’s confidence and to stop oral
malodour.
Table I. Active ingredients for oral malodour treatment in each preparation
Ingredients
Functions
Preparations
Botanical extracts
Antimicrobial [52-55]
Tablet [56]
Cetylpyridinium
Antimicrobial [57-59]
Mouthrinse [58], mouthspray [61], dentifrice [62], oral
chloride
gel [55, 64, 65]
Chlohexidine
Antimicrobial [72]
Mouthrinse [73, 74]
Chlorine dioxide
Cysteine and methionine oxidizing agent [76],
Mouthwash [75], dentifrice [80], mouthspray [81, 82],
antimicrobial [77]
chewing gum [83]
Amino acid containing sulphur oxidizing agent
Dentifrice [86]
Dehydroascorbic acid
[86]
Ingredients
Essential oils
Functions
Preparations
Antimicrobial [88], antiseptic and anticaries
Mouthwash [87, 91], mouthspray [91], dentifrice
[92]
[91, 92], lipstick [96]
Hydrogen peroxide
VSCs reduction [97]
Dentifrice [97]
Sodium bicarbonate
VSCs reduction [98-100]
Mouthrinse [99], dentifrice [100]
Triclosan
Antimicrobial [101]
Dentifrice [101-109]
Zinc salts
Antimicrobial [110, 116, 117]
Mouthrinse [65, 79, 113, 117], dentifrice [112, 113, 116],
chewing gum [117]
Activated carbon
Odorant absorber [120]
Dentifrince, chewing gum, scraper [120]
Enzyme
Tongue coating bacterial reduction
Oral biofilm [122, 123], dentifrice [105]
Acknowledgements
The authors acknowledge Kagawa University on library and data base accesses
and Mae Fah Luang University on facility support for this manuscript preparation.
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