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Volatile sulfur compounds: the cause of bad breathAlbert Tangerman a & Edwin G. Winkel aa Center for Dentistry and Oral Hygiene, Department of Periodontology, University ofGroningen, University Medical Center Groningen, Groningen, The NetherlandsAccepted author version posted online: 25 Oct 2012.

To cite this article: Albert Tangerman & Edwin G. Winkel (2012): Volatile sulfur compounds: the cause of bad breath,Phosphorus, Sulfur, and Silicon and the Related Elements, DOI:10.1080/10426507.2012.736894

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Volatile sulfur compounds: the cause of bad breath

Albert Tangerman* and Edwin G. Winkel

Center for Dentistry and Oral Hygiene, Department of Periodontology, University of Groningen,

University Medical Center Groningen, Groningen, The Netherlands.

Email: atangerman@hotmail.com

Title for running head: Volatile sulfur compounds and bad breath

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Abstract

Bad breath or halitosis is a concern for millions of people. Halitosis is subdivided into intra-oral

and extra-oral halitosis, depending on the place where it originates. About 90% of halitosis

originates within the oral cavity and include bacterial reservoirs such as the dorsum of the

tongue, where anaerobic bacteria degrade the sulfur containing amino acids cysteine and

methionine into the foul smelling volatile sulfur compounds (VSCs) hydrogen sulfide (H2S) and

methyl mercaptan (CH3SH). Tongue coating is considered to be the most important source of

VSCs. Intra-oral halitosis can be treated effectively by cleaning the tongue with a tongue-scraper

and by using special mouthrinses. Extra-oral halitosis can be subdivided into non-blood-borne

halitosis such as halitosis from the nose and the respiratory tract, and into blood-borne halitosis.

The majority of patients with extra-oral halitosis have blood-borne halitosis, frequently caused

by the odorous VSC dimethyl sulfide (CH3SCH3). Extra-oral halitosis, covering about 5-10% of

all cases of halitosis, might be a manifestation of a serious disease. It is of utmost importance to

differentiate between intra-oral and extra-oral halitosis, which can easily be done by comparing

mouth breath with nose breath. The importance of applying odor characteristics in halitosis

research is also highlighted.

Keywords – Bad breath, halitosis, volatile sulfur compounds

Introduction

Most adults suffer from occasional bad breath with an estimated 10 to 30 % of the USA1 or

Chinese2 population experiencing halitosis on a regular basis. This can lead to personal

discomfort and social isolation. Halitosis is unquestionably one of the biggest taboos in our

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society. The general population is still poorly informed about the causes and treatment of

halitosis. Many people still believe that halitosis originates in the stomach, which is seldom the

case. The oesophagus, which connects the stomach with the mouth, is not an open tube and is

normally collapsed3, thereby preventing odorous gases to escape from the stomach to the mouth.

Moreover, no evidence exists for the formation of odorous substances in the stomach. Halitosis is

rarely a gastrointestinal condition4. Regrettably, many patients with halitosis have undergone an

unnecessary gastroscopy before visiting a breath clinic. Halitosis can be subdivided into intra-

oral and extra-oral halitosis, depending on the place where it originates5,6,7. Most reports now

agree that the most frequent sources of halitosis (some 90%) exist within the oral cavity and

include bacterial reservoirs such as the dorsum of the tongue, saliva and periodontal pockets,

where anaerobic bacteria degrade sulfur containing amino acids to produce the foul smelling

volatile sulfur compounds (VSCs) hydrogen sulfide (H2S), methyl mercaptan (MM) and to a

lesser extent dimethyl sulfide (DMS)3,8,9. These VSCs are the predominant elements of intra-oral

halitosis although some do believe that other odorous volatiles, such as certain amines and fatty

acids, may play a role10,11,12. Oral malodour can now be treated effectively, especially by the use

of a tongue scraper and certain mouth-rinses5,7,9,13,14. In contrast to intra-oral halitosis less

attention has been paid to extra-oral halitosis3,5,9,13,15,16. Extra-oral halitosis, covering about 5-

10% of all cases of halitosis, might be a manifestation of a serious disease for which treatment is

much more complicated. It is of utmost importance to differentiate between intra-oral and extra-

oral halitosis. This can be easily done by comparing mouth breath with nose breath6,9,13,15.

Among the host of patients with extra-oral halitosis, only a few have been investigated using

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analytical techniques to identify the volatile odorous compounds associated with the odour5,16.

This is highly important, in order to diagnose the cause and to find a possible treatment.

Results and Discussion

Odor characteristics. Important in halitosis research are the odor index (O.I.) and the odor

threshold values. In odor research, there are three different odor thresholds that have been

determined: (1) the perception threshold, (2) the recognition threshold and (3) the

objectionability threshold17. At the perception threshold concentration one is barely certain that

an odor is detected, but it is too faint to identify further. The thresholds normally used are those

for 50% and for 100% of an odor panel. The 100% recognition threshold is the concentration at

which 100% of the odor panel defined the odor as being representative of the odorant being

studied. The objectionability threshold represents the lowest concentration of an odorant

producing an objectionable smell. The O.I. is the ratio between the vapor pressure of an odorant

and the 100% recognition threshold, in other words, the ratio of the driving force to introduce an

odorant into the air versus the ability of an odorant to create a recognized response. Volatiles

with an O.I. > 1,000,000 are classified as having a high odor potential (mercaptans, sulfides,

alkenes), volatiles with an O.I. between 100,000 and 1,000,000 as having a medium odor

potential ((di- and tri-alkyl amines, ethers) and volatiles with an O.I. < 100,000 as having a low

odor potential (alcohols, alkanes, acetic acid, propionic acid, butyric acid). Usually, volatiles

with the highest odor index and the lowest recognition threshold are the most odorous ones. Of

all chemical classes, the unsaturated mercaptans (allyl mercaptan in garlic) and the unsaturated

sulfides (allyl methyl sulfide in garlic) are the most odorous ones, followed by saturated

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mercaptans (propyl mercaptan in onion, methyl mercaptan, hydrogen sulfide), disulfides

(dimethyl disulfide) and sulfides (methyl propyl sulfide in onion and dimethyl sulfide).

Table 1 shows the most common odorous volatile sulfur compounds, some amines and n-butyric

acid, together with some of their known odor characteristics17. Butyrate and the amines indole,

skatole and cadaverine have often been claimed to be contributors to halitosis, in particular to

intra-oral halitosis10,11,12, because of their low odor thresholds and high odor power11. Such a

contribution was contradicted by others8,18,19, mainly because oral pH does not favor their

volatilization. As is clear from Table 1, a low odor threshold does not automatically imply a high

O.I. Although butyrate and skatole have very low odor thresholds, comparable with the VSCs,

the volatilities of these compounds are very low resulting in a low O.I. < 100,000, indicating a

low odor potential. In our previous studies5,6,16 we have stressed that, to prove that a volatile

might contribute to halitosis, one has to measure the concentration of the suggested odorant in

the breath, to simulate the breath by making artificial gas mixtures with the measured

concentration of the odorant and to smell these gas mixtures. These artificial gas mixtures must

produce a certain smell similar to the halitotic breath, in order to conclude that the odorant is an

important contributor to halitosis. In other words, the concentration of the odorant in the halitotic

breath must exceed the threshold of objectionability of that odorant. This was valid for MM and

H2S in intra-oral halitosis and for DMS in extra-oral blood-borne halitosis5,6,16. The

concentrations of MM and to a lesser extent of H2S in intra-oral halitosis and of DMS in extra-

oral blood-borne halitosis were well above their thresholds of objectionability. Artificial gas

mixtures with the same concentrations had a smell similar to the halitotic breath, proving that

these VSCs are the major contributors to intra-oral, respectively extra-oral blood-borne halitosis.

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Intra-oral halitosis. Intra-oral halitosis, the most frequent form of halitosis (about 90%), may be

indicative of either oral diseases, such as periodontal diseases, or the presence of excessive

bacterial reservoirs on the tongue. The pathogenesis of intraoral halitosis is associated with the

bacterial degradation of sulfur-containing amino acids (methionine, cystine, and cysteine) into

volatile sulfur compounds (VSCs) of which MM and H2S are the major compounds. It appears

that MM and to a lesser extent H2S are the predominant causative factors of intra-oral

halitosis5,6,20. The VSCs have a very high odor potential17 (see also Table 1). Recently, van den

Velde et al21 measured for the first time the concentrations of indole, skatole and organic acids

(acetic acid, butyric acid) in breath of healthy volunteers and in patients with intra-oral halitosis

(see also discussion above). They found that the concentrations of the aromatic amines indole

and skatole and of butyric acid were extremely low in both groups, in fact too low to be detected

organoleptically, thus far below the objectionability threshold. They also concluded that MM and

H2S are the main contributors to intra-oral halitosis and that the roles of other compounds, like

amines and organic acids, seem insignificant.

Tongue coating is considered to be the most important source of VSCs in intra-oral halitosis,

most of the odor coming from the dorsoposterior surface of the tongue9,13,22,23. A reduced saliva

flow during sleep favours anaerobic bacterial putrefaction, giving rise to the so called “morning

breath”, a transient condition which disappears after a meal8,24. In an estimated 10 to 30% of the

population the problem remains more persistent1 and halitosis is active during the whole day.

The latter condition of chronic intra-oral halitosis can now be treated very effectively by

removing the tongue coating by means of a tongue scraper and by appropriate

mouthwashes5,7,9,13,14,25, some containing zinc salts to bind the VSCs.

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Extra-oral halitosis. Extra-oral halitosis can be subdivided into non-blood-borne halitosis such

as halitosis from the nose and the respiratory tract, and into blood-borne halitosis5,16. The

majority of patients with extra-oral halitosis have blood-borne halitosis. Malodorous volatile

substances can be absorbed from anywhere in the body (e.g. mouth, stomach, intestines, liver)

into the bloodstream and later transferred to the pulmonary alveoli. Pulmonary excretion of these

volatiles into the alveolar air then causes halitosis, if the malodorous volatiles are present in

objectionable concentrations in the breath. Blood-borne halitosis5,16 has been reported to arise

from some systemic diseases, metabolic disorders, medication and from the use of certain foods

(Table 2). Most of the reported cases of blood-borne halitosis are also caused by odorous volatile

sulfur compounds, such as DMS. However, the nature of the compounds differs from that of the

volatiles found in halitosis of oral origin. While intra-oral halitosis is largely caused by CH3SH

and to a lesser extent by H2S, these compounds cannot be found in blood-borne halitosis. In-vitro

experiments have shown37 that the thiol CH3SH, containing a free –SH group, immediately

reacts with whole blood within seconds, resulting in irreversible binding and oxidation, thereby

preventing transportation of CH3SH from the blood into alveolar air and thus into breath. The

same holds for H2S. This is not true for DMS (CH3SCH3), a neutral molecule which is stable in

whole blood and can be transported from blood into alveolar air and breath. Other volatiles found

in blood-borne halitosis are also stable in whole blood. The neutral nature of most volatiles found

in blood-borne halitosis is one of the reasons why these compounds are difficult to remove from

the breath, this in contrast with the very reactive thiols CH3SH and H2S in intra-oral halitosis,

which thiols can be effectively removed from the breath, e.g. by binding with zinc salts5,7.

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Therapy of extra-oral halitosis should be aimed at diminishing the concentration of the odorant

by combating an underlying disease, by some diet factors or by adjustments in medications.

Extra-oral halitosis, covering about 5-10% of all cases of halitosis, might be a manifestation of a

serious disease. It is of utmost importance to differentiate between intra-oral and extra-oral

halitosis, which can easily be done by comparing mouth breath with nose breath. Patients with

intra-oral halitosis only have bad breath from the mouth but not from the nose. The VSCs H2S

and MM, typical for intra-oral halitosis, were not found in nasal exhalations of patients with

intra-oral halitosis6. All patients with extra-oral blood-borne halitosis have bad breath from both

the mouth and the nose6,13 because of the presence of the odorous volatiles in alveolar air.

Patients with extra-oral non-blood-borne halitosis (minority) should also have bad breath from

both the mouth and the nose, except those patients by whom the origin of bad breath is situated

in the upper respiratory tract above the throat, e.g. in the nose. The latter patients should have

only bad breath from the nose and not from the mouth.

Experimental

Standard gas chromatography using a specific sulfur detector5,6,38 can perfectly detect intra-oral

and extra-oral blood-borne halitosis, the latter when due to sulfur volatiles. It can easily

differentiate between these two forms of halitosis. A newly developed portable gas

chromatograph, the OralChroma, is a very sensitive apparatus for measuring VSCs and is also

perfectly capable to detect intra- as well as extra-oral halitosis, when cau and to differentiate

between these two forms39. The often used Halimeter40 measures the sum of the three VSCs and

cannot differentiate between these VSCs. The Halimeter highly underestimates DMS and is

unable to detect extra-oral blood-borne halitosis39, when due to DMS. Besides gas

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chromatography, the breath was evaluated organoleptically by using a 0 to 5 scale6,7. Sampling

procedures of breath have been described before6,7,39.

Conclusions

Application of odor characteristics, such as odor threshold values and the odor index, is highly

important in halitosis research. To prove if an odorant contributes to halitosis, simulation

experiments by producing artificial gas mixtures with the same concentration of the odorant as

found in the halitotic breath, are of great value. Intra-oral halitosis is by far the most frequent

form of halitosis and is caused by methyl mercaptan and to a lesser extent by hydrogen sulfide. It

can be treated very effectively by removing the tongue coating by means of a tongue scraper and

by appropriate mouthwashes The large majority of extra-oral halitosis is extra-oral blood-borne

halitosis due to the presence of VSCs, in particular DMS. Therapy is more difficult.

References

[1] Meskin, L. H. J. Am. Dent. Assoc. 1996, 127, 1282-1286.

[2] Liu, X. N.; Shinada, K.; Chen, X. C.; Zhang, B. X.; Yaegaki, K.; Kawaguchi, Y. J. Clin.

Periodontol. 2006, 33, 31-36.

[3] Attia, E. L.; Marshall, K. G. Can. Med. Assoc. J. 1982, 126, 128-135.

[4] Tangerman, A.; Winkel, E. G.; de Laat, L.; van Oijen, A. H.; de Boer, W. A. J. Breath Res.

2012, 6, 017102.

[5] Tangerman, A. Int. Dent. J. 2002, 52 (Suppl. 3), 201–206.

[6] Tangerman, A.; Winkel, E. G. J. Clin. Periodontol. 2007, 34, 748-755.

[7] Winkel, E. G. Clinical Periodontology and Implant Dentistry, 5th ed.; Blackwell

Munksgaard, Oxford, 2008; pp. 1325-1340.

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[8] Tonzetich, J. J. Periodontol. 1977, 48, 13-20.

[9] Rosenberg, M. J. J. Am. Dent. Assoc. 1996, 127, 475-482.

[10] Goldberg, S.; Kozlovsky, A.; Gordon, D.; Gelernter, I.; Sintov, A.; Rosenberg, M. J. Dent.

Res. 1994, 73, 1168-1172.

[11] Greenman, J.; El-Maaytah, M.; Duffield, J.; Spencer, P.; Rosenberg, M.; Corry, D.; Saad,

S.; Lenton, P.; Majerus, G.; Nachnani, S. J. Am. Dent. Ass. 2005, 136, 749-757.

[12] Porter, S. R.; Scully, C. Brit. Med. J. 2006, 333, 632-635.

[13] Richter, J. L. Compend. Contin. Educ. Dent. 1996, 17, 370-388.

[14] Yaegaki, K.; Coil, J. M.; Kamemizu, T.; Miyazaki, H. Int. Dent. J. 2002, 52 (Suppl. 3),

192–196.

[15] Durham, T. M.; Malloy, T.; Hodges, E. D. Geriatrics, 1993, 48, 55-59.

[16] Tangerman, A.; Winkel, E. G. J. Breath Res. 2010, 4, 017003.

[17] Verschueren, K. 1983 Handbook of Environmental Data on Organic Chemicals. 2nd ed.;

Van Nostrand Reinhold Company: New York, Cincinnati, Toronto, London, Melbourne. 1983;

pp 42-59.

[18] Tonzetich, J.; Eigen, E.; King, W. J.; Weiss, S. Archs. Oral Biol. 1967, 12, 1167-1175.

[19] Kleinberg, I.; Westbay, G. Crit. Rev. Oral Biol. Med. 1990, 1, 247-259.

[20] Awano, S.; Koshimune, S.; Kurihara, E.; Gohara, K.; Sakai, A.; Soh, I.; Hamasaki, T.;

Ansai, T.; Takehara, T. J. Dent. 2004, 32, 555-559.

[21] Van den Velde, S.; van Steenberghe, D.; van Hee, P.; Quirynen, M. J. Dent. Res. 2009, 88,

285-289.

[22] Tonzetich, J.; Ng, S. K. Oral Med. 1976, 42, 172-181.

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[23] Yaegaki, K.; Sanada, K. J. Periodontal Res. 1992, 27, 233-238.

[24] Suarez, F.; Furne, J.; Springfield, J.; Levitt, M. D. J. Dent. Res. 2000, 79, 1773-1777.

[25] Quirynen, M. J. Clin. Periodontol. 2004, 31, 506-510.

[26] Tangerman, A.; Meuwese-Arends, M. T.; Jansen, J. B. Lancet 1994, 343, 483.

[27] Tangerman, A. J. Chromatogr. B, 2009, 877, 3366-3377.

[28] Lu, D. P. Oral Surg. Oral Med. Oral Pathol. 1982, 54, 521-526.

[29] Preti, G.; Clark, L.; Cowart, B. J.; Feldman, R. S.; Lowry, L. D.; Weber, E.; Young, I. M. J.

Periodontol. 1992, 63, 790-796.

[30] Manolis, A. Clin. Chem. 1983, 29, 5-15.

[31] Mudd, S. H.; Levy, H. L.; Tangerman, A.; Boujet, C.; Buist, N.; Davidson-Mundt, A.;

Hudgins, L.; Oyanagi, K.; Nagao, M.; Wilson, W. G. Am. J. Hum. Genet. 1995, 57, 882-892.

[32] Mitchell, S. C.; Smith, R. L. Drug Metab. Dispos. 2001, 29, 517-521.

[33] Suarez, F.; Springfield, J.; Furne, J.; Levitt, M. Am. J. Physiol. 1999, 276, G425-430.

[34] Block, E.; Naganathan, S.; Putman, D.; Zhao, S-H. Pure & Appl. Chem. 1993, 65, 625-632.

[35] Gahl, W. A.; Infelfinger, J.; Mohan, P.; Bernardini, I.; Hyman, P. E.; Tangerman, A.

Pediatr. Res. 1995, 38, 579-584.

[36] Besouw, M.; Blom, H.; Tangerman, A.; de Graaf-Hess, A.; Levtchenko, E. Mol. Genet.

Metab. 2007, 91, 228-233.

[37] Blom, H. J.; Tangerman, A. J. Lab. Clin. Med. 1988, 111, 606-610.

[38] Tangerman, A. J. Chromatogr. 1986, 366, 205-216.

[39] Tangerman, A.; Winkel, E. G. J. Breath Res. 2008, 2 017010.

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[40] Rosenberg, M.; Kulkarni, G. V.; Bosy, A.; McCulloch, C. A. J. Dent. Res. 1991, 11, 1436-

1440.

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Table 1. Odor characteristics of volatile sulfur compounds, amines and n-butyric acid.

Formula Name

Odor qualification Odor Index 100% Odor recogn. conc.

H2S hydrogen sulfide rotten eggs 17,000,000 1000 ppbCH3SH methyl mercaptan pungent, rotten cabbage 53,300,000 35 ppbCH3SCH3 dimethyl sulfide unpleasantly sweet 2,760,000 100 ppbCH2=CHCH2SH allyl mercaptan garlic-like > 300,000,000 0.05 ppbCH2=CHCH2SCH3 allyl methyl sulfide garlic-like > 300,000,000 CH3CH2CH2SH propyl mercaptan unpleasant, pungent 263,000,000 0.7 ppbCH3CH2CH2SCH3 methyl propyl sulfide CS2 carbon disulfide slightly pungent 1,600,000 900 ppbNH3 ammonia pleasantly sweet 167,300 55,000 ppb(CH3)2NH dimethyl amine fishy, ammoniacal 280,000 6,000 ppb(CH3)3N trimethyl amine fishy, ammoniacal 493,500 4,000 ppb sskkaattoollee fecal-like 30,000 0,4 ppbCH3CH2CH2COOH nn--bbuuttyyrriicc aacciidd rancid 50,000 20 ppba In ppb; 24 ppb = 1 nmol/l at 20C and 760 mm Hg. b Experimentally determined by us.

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Table 2. Conditions of extra-oral blood-borne halitosis

Causes of blood-borne halitosis Odorant References Systemic diseases Hepatic failure/liver cirrhosis Dimethyl sulfide 5, 26,27 Uremia/kidney failure Ammonia, dimethyl amine,

trimethyl amine 28,29,30

Diabetic ketoacidosis, diabetes mellitus Acetone 28,29,30 Metabolic disorders Isolated persistent hypermethioninemia Dimethyl sulfide 31 Unknown disorder Dimethyl sulfide 6,27 Fish odor syndrome Trimethylamine 32 Food Garlic Allyl methyl sulfide 33,34 Onion Methyl propyl sulfide 34 Medication Disulfiram Carbon disulfide 30 Dimethyl sulfoxide Dimethyl sulfide 3,28 Cysteamine Dimethyl sulfide 35,36

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