The History of Professional Formulas

Utilizing Stabilized Chlorine Dioxide (ClO2)

For Efficacious Treatment of Bad Breath

 

1965-2000

Prepared for

4th International Conference on Oral Malodor

UCLA School of Dentistry

August 1999



Bad Breath:  From Mythology to Diagnosis to Clinical Therapies to Oxygenating Consumer Products.

A review of the scientific literature. 

 

 

Early Research on Bad Breath:

 

Billions of dollars are invested in the oral care industry every year, by a public generally misinformed as to why they have bad breath.  According to experienced researchers, up to 50% of the population suffers enough to seek help beyond standard oral care.[1]

 

Up until a few years ago, the general population was fed the commonly-held fable that bad breath originates in the digestive system.  This myth has been destroyed by acceptable scientific studies as well as efforts by governmental agencies to halt the continuation of false information, intended to confuse the public.[2],[3]

 

It is generally agreed, as the result of work by Dr. John Tonzetich of the University of British Columbia and co-workers that volatile sulfur-containing compounds are the central elements of bad breath.[4] Several investigators identified that Gram-negative anaerobes are the bacteria responsible for the production of what are referred to commonly as VSCís (including, but not limited to Hydrogen Sulfide and Methyl Mercaptan).[5]  The anaerobic bacterial population, breeding deep below the surface of the tongue and often in the throat and tonsil area, have the ability to break down several amino acids, found in proteins.  The resulting by-products of this degradation become the VSCís.[6]  In order to fully understand what VSCís mean the most common is Hydrogen Sulfide (the "rotten egg" smell).[7]

 

In a nutshell, everyone in the world has bad breath at one time or another.  This is because everyone harbors the bacteria that create the sulfur odors.  These are not bad bacteria, but "bugs" we all need in order to help us digest proteins.[8]  The bacteria were designed specifically to degrade the building blocks of proteins, which are amino acids.  Unfortunately a big percentage of the public have conditions which allow the bacteria to create sufficient sulfur compounds (>75ppb of Sulfides) which are enough to register as bad breath.[9] 

 

Common Contributors to Bad Breath:

 

Alcohol:    Dryness in the oral cavity, including the tongue, palate and throat, enable VSCís to escape into the mouth air and contribute to oral malodor.[10]  This is because a dry mouth provides a perfect environment for the anaerobic (oxygen-hating) bacteria.  Aside from Xerostomia (chronic dry mouth) and aging, most cases of dry mouth are produced by the drying action of alcohol.  Alcohol happens to be the most common ingredient in commercial mouthwashes and may contribute to bad breath more than eliminating it.[11]

 

Medications:    Recently, prescription and over the counter medications, which have dry mouth as a side-effect have become very popular.   Seven of the top 10 prescribed medications have dry mouth as a common side effect.  These generally include anti-depressants, high blood pressure medication, and antihistamines.[12]

 

Sugar:   Sugar, commonly found in very popular breath mints (including, but not limited to Altoids), chewing gum, and soft drinks contributes fermentable carbohydrates which in turn stimulates the production of VSCís.[13]

 

Proteins:   By providing a source of proteins, whose amino acids are easily degraded into VSCís, all one needs to do is eat any dairy food.  These proteins are high in the amino acids which after contacting the anaerobes can become the VSCís Hydrogen Sulfide and Methyl Mercaptan.7

 

Smoking:    All smoking (cigarettes, cigars, pipes, etc) decrease salivary flow, which leads to dry mouth and bad breath.11

 

Coffee:  All types of coffee, with caffeine or without, contain a high concentration of acids (which stimulate bacterial reproduction) and other agents which cause oral tissue to dehydrate.11

 

Garlic & Onions:  Both of these foods contain Mercaptans as their odorous component. Mercaptans are one of the several VSCís produced by bacteria, so the ingestion of these foods will add a powerful component to bad breath.11

           

Hormonal Changes:   Oral VSC production in women varies accordance with the menstrual cycle, which also includes the introduction of Estrogen/Progesterone therapies during menopause.[14]

 

 

 

Clinical Therapy:

 

      In the early 1990ís a handful of pioneering dentists started diagnosing bad breath in their offices[15].  Armed with a sulfide gas monitor (Halimeter), they measured the level of bad breath that was exhaled by their clientele and then performed in office therapy, along with home care, which included the use of chlorine dioxide products, which have become the "gold-standard" in fighting bad breath.[16]

 

Clinic treatment was divided into 4 schools of thought:

         The use of low-concentration chlorine dioxide containing products, which are still available only through Multi-Level-Marketing.[17]

         The use of unstabilized chlorine dioxide liquid in the clinic and after treatment.14

         The use of concentrated and stabilized chlorine dioxide containing products for in-office therapy and for long term home care.15

         The use of the astringent, Zinc Chloride alone as an anti-microbial therapy, but not as an oxygenating agent.8

 

            Various organoleptic (smelling) testing methods have been used over the years to establish a reproducible method of scoring the degree and intensity of bad breath.[18]  A significant development in clinical treatment was the introduction of the Halimeter[19], which allowed doctors to gather significant readings on a long term basis to determine the extent of the Halitosis, the source of the problem (by ruling out the digestive system as a source), and which formulas worked best.  The California Breath Clinics were the first to use Dr. Yaegakiís sulfide readings of 75 ppb as the highest acceptable level and the first to use a pharmaceutical grade chlorine dioxide in their products to maintain sulfide readings at this level or below.[20]

 

            Although several Zinc compounds are anti-microbial in nature, the Chloride salt creates a strong burning effect and unfortunately this side effect leads to poor patient compliance.  Patient drop-off has been high with this type of home treatment.

 

            On the other hand, true "oxygenating" compounds, or more accurately oxidizing agents, continue to thrive in the dental office.  There are various ways to create "oxygenating compounds".  The most common is through acidifying sodium chlorite (NaClO2) to create ClO2 (chlorine dioxide).  Unfortunately, the production of the oxidation is very sluggish because they rely merely on the small difference of pH levels between the formula and the userís saliva.  When these salts are in their Chlorate form, they can no longer produce oxygen "oxygenate", or oxidize the sulfhydryl bonds.26

 

The most efficient method and the technique which produces copious amounts of ClO2 on demand, uses latent precursors through a patented technique and is known as Pharmagene.  In addition to creating chlorine dioxide through pH changes, Pharmagene (known as OXYD-8 to the public) also uses the proteins in bacteria cell walls as a means of generating MORE ClO2.  This creates a situation whereby OXYD-8 containing compounds will work "beyond the call of duty" and more Oxygenation when the patientís breath is worse.  There is virtually no end to its ability to create ClO2 compared to the acidification only process.

 

There are also concerns about Hydrogen Peroxide use for oxygenating because of production of free radicals.  Bleach components, necessary in one version of chlorine dioxide oral rinse, can produce potentially cancer-causing trihalomethanes.19 

 

Consumer products and home therapies:

 

Is brushing and flossing effective in reducing Bad Breath, or is Tongue Scraping the simple Answer to a Complicated Problem? 

 

A study by Yaegaki et. al., showed that there was a significantly higher concentration of VSCís produced from the far back portion of the tongue surface than the tooth and surrounding gum areas of the oral cavity.  In fact, an increase in the methyl mercaptan component of VSCís coming from tongue coating, contribute to the initiation of periodontal disease instead of the age-old thought that periodontal disease contributes to bad breath.  This has lead to therapies, attempting to reduce VSCís in the entire oral cavity and throat area instead of focusing primarily on tooth brushing and flossing as the basic oral hygiene regimen.7

 

Does this mean that cleaning the tongue is the answer[21]?  Yes and no.  Kleinberg and others have pointed out that these are anaerobic bacteria and by definition they cannot survive on the surface of the tongue.  (Oxygen present in inhaled air would kill off the anaerobes instantly if this were true.) So where do the bacteria live.  They are well protected deep below the papillae (the thin fibers) that make up the rear 1/3 portion of the tongue and continue below the tongueís surface into the throat and into tonsil crypts (if tonsils are present). 

 

Furthermore, these bacteria are part of the normal oral flora, stressing the fact that they need to be there to perform the 1st step in human digestion.  One of the worst therapies for the treatment of bad breath is the use of antibiotics, which happens to be an easy, but ill-informed 1st choice for many physicians. Patient histories gathered by the doctors of the California Breath Clinics have shown that bad breath increases with a history of long term antibiotic use (in particular Tetracycline, Minocycline or Minocin for acne)7. This is because broad spectrum antibiotics tend to kill off a wide array of bacteria, allowing beneficial bacteria and yeasts to overgrow the environment. With long antibiotic therapy, anaerobic sulfur producing bacteria involved in bad breath production (typically Fusobacterium Nucleatum, Treponema Denticola, and various Bacteroides) increase as time goes on.

 

Anti-Halitosis formulas proven in clinical treatment which are now available to consumers: 

 

        Consumer products designed to stop bad breath are broken down into several niches, such as Mouthwash, Toothpaste, Sprays, Drops, Chewing Gum, and Mints.  Previous information presented in this review has already detailed the lack of effectiveness and compliance of formulas containing Alcohol, Sodium Lauryl Sulfate, or Zinc Chloride.

 

           So what options are left for someone desiring to free themselves of the burden of bad breath?  In the last few years, sufferers have contacted a growing number of dentists who perform an in-office diagnosis and treatment, with virtually all of them using  various chlorine dioxide products for clinically-proven effectiveness.  A long list of scientific papers and documentation discuss the rapid and continuing reduction of VSCís through these chlorine dioxide rinses and toothpastes.  As far back as the mid-1960ís oral rinses containing chlorine dioxide have been used for this problem.  The basic text used for water purification "Chlorine Dioxide"[22] written by Masschelein in 1979, outlined effective and safe recipes for mouthwash and toothpaste containing chlorine dioxide.  Recently, a patented process used to stabilize chlorine dioxide in both a liquid and tabletized form, were utilized so that chlorine dioxide could be used in commercial products, requiring long shelf life in retail stores.  These systems allow chlorine dioxide to be produced "on demand" for its full potency on each use. Products using this Pharmagene26 (liquid) and Aspetrol[23] (tabletized) technology have been available through Breath Clinics, on the internet and through direct marketing in the brands commonly known as TheraBreath, AktivOxigen, PerioTherapy, and TheraBrite, which will soon be available to the public through retail chains.

 

Safety of Chlorine Dioxide:

 

            The safety of chlorine dioxide has long been established.  It was discovered by Davy in 1837 and was soon used to purify drinking water in European cities. Michel and Wondergem have written scientific articles on  ClO2 in water purification and as a post disinfectant.  Various studies by Abdel-Rahman[24],  Lubbers[25], and others have detailed various scenarios whereby long term digestion of highly concentrated ClO2 solutions by humans have not produced any negative side effects.  Commercial use continues, not only in water purification, but in antimicrobial therapy and food safety technology.  Millions of people digest chlorine dioxide when they drink water on an airplane, because all water on airliners is purified with ClO2, since itís a closed system.[26] This is because ClO2 never breaks down into chlorine ions (itís always bonded to an oxygen atom!).

 

Effectiveness of Chlorine Dioxide formulas in reducing VSCís vs. commercially available products.

 

A recent study compared chlorine dioxide products to a commonly used regimen of a popular alcohol based mouthwash and Toothpaste, with respect to gum bleeding and other factors related to oral hygiene and bad breath.  The study by the periodontist Spindler showed that the chlorine dioxide products scored better than said products in every category of the study.[27]  In a UK study by Lynch et. al at the Royal London School of Medicine and Dentistry[28], six different products were tested with respect to their ability to reduce bad breath.  In order from best formula to worst were:  1)  an oral rinse containing 1000 ppm of stabilized ClO2, 2) a non-stabilized ClO2 oral rinse,  3)  an oral rinse containing 500 ppm of stabilized ClO2,  4)  an alcohol based oral rinse,  5)  an alcohol based oral rinse,  6)  a gelatin capsule containing parsley seed oil, which did not reduce any VSCís at all.  Another study compared a stabilized chlorine dioxide oral rinse vs. Listerine and sterile water in their ability to reduce bacterial levels produced through the dental treatment.  Again, the study showed that stabilized chlorine dioxide surpassed the effectiveness of Listerine.[29]

 

The Most Recent Studies on Anti-Halitosis Formulas, presented by leading scientists in the field:

 

        At the 4th  International Symposium on Oral Malodor, held at UCLA in August of 1999, various papers were presented outlining the effectiveness of various formulas to halt bad breath.  One of the studies below (#3) even indicates an additional benefit  a decrease in the number of anaerobic bacteria present after use.

 

1.                  Frascella, Gilber, Fernandez, and Hendler showed that oral products containing at least 1000 ppm of ClO2 had the ability to reduce oral malodor for at least 8 hours.  (Efficacy of a Stabilized Chlorine Dioxide containing Mouthrinse in Oral Malodor.)

 

2.                  Chang, Greenman, Allaker, and Lynch of the Royal London School of Medicine and Dentistry presented a paper demonstrating that chlorine dioxide irreversibly inhibits the change of the amino acid Cysteine to Hydrogen Sulfide, commonly known as the rotten egg smell.  (Reduction of Oral Malodor by a Stabilized Chlorine Dioxide Containing Mouthrinse; Likely Mechanisms of Action in Vivo.)

 

3.                  Acikgoz, Devrim, Aldikacti, Kayipmaz, and Keles of the Department of Periodontics of the University Dental School in Samsun Turkey showed that the use of TheraBreath brand stabilized chlorine dioxide products showed a statistically significant decrease in bad breath and anaerobic bacteria colonies throughout the oral cavity, by the gold standard test - Flame Gas Chromatography and the Interscan Halimeter.  (Effects of Oxygenating TheraBreath (Stabilized Chlorine Dioxide) on Bad Breath measured by GCF and the Halimeter)

 

 

Conclusion

 

Commercial mouthwash and breath freshener advertisements continue to reinforce to the public the stigma of bad breath.  The olfactory sense can fatigue and patients may become insensitive to their own halitosis, only being made aware of it by other.  In the past, treatment for halitosis has been difficult and frustrating for both patients and clinicians.  With newer understanding of the oral and bacterial mechanisms involved in the development of halitosis along with effective oxygenating formulas for home use, treatment has become more effective.  Now that these chlorine dioxide formulas are moving from clinical therapy directly to the retail market, the public will be able to obtain them  easily and utilize them for their daily oral hygiene routine.

 

 

 



[1] Tonzetich, J. Sources, Measurements and Implications of Oral Malodor.  Abstracts presented at the International Association for Dental Research Ė Symposium on Oral Malodor, April, 1991 Acapulco, Mexico.

 

[2] Better Business Bureau Advertising Review Programs, Council of Better Business Bureaus, Inc. National Advertising Division Press Release "BreathAsure Agrees To Modify Unsubstantiated Ad Claims", April, 16, 1997.

 

[3] Federal Court Order, November, 18, 1998. ďBreathAsure claims halted by Federal CourtĒ, Quackwatch.com.

 

[4] Tonzetich, J., Production and origin of oral malodor:  Review of mechanisms and methods of analysis. J. Periodontology, 48, 13, 1977.

 

[5] McNamara, T.F., Alexander, J.F., and Lee, M.. The role of microorganisms in the production of oral malodor, Oral Surg., 34, 41, 1972.

 

[6] Traudt, M. and Kleinberg, I., Bacteria in human dental plaque responsible for its oxygen uptake activity.  Journal of Dental Research. 67 (Abstr) 204, 1998.

 

[7] Katz, Harold.  The Bad Breath Bible, KDS Publications., Pomona, CA.  1999.

 

[8] Kleinberg, I., Westbay, G.  Oral Malodor, Critical Reviews in Oral Biology and Medicine Vol. 1, Issue 4 pages 247-259, 1990.

 

[9] Yaegaki, K, Sanada, K.  Effects of a two-phase oil-water mouthwash on Halitosis.  Clinical Prev. Dent. 1992; 14:15-19.

 

[10] DiSabato-Mordarski, T. and Kleinberg, I.  Intra-oral variation in the residual saliva on the oral tissues.  Journal of Dental Research., 68 (Absr.), 316, 1989.

 

[11] Wegman, E.A., Berman, A., Pokorny, C.S., How to Investigate the Patient with Halitosis.  Modern Medicine of South Africa. July 1999.  P. 32-38.

 

[12] Silverman, H., The Pill Book.  Bantam Books, New York, 8th edition. 1998

 

[13] Hartles, R.L. and Wasdell, M.R., The metabolism of the oral flora. II.  The oxidation of some sugars by mixed human saliva.  Biochem. Journal., 56, 353, 1955.

 

 

 

 

[14] Tonzetich, J, Preti, G., Huggins, G:  Changes in concentration of volatile sulfur compounds in mouth air during the menstrual cycle.  Journal of Internal Medicine Research.  5:245-254, 1978.

 

[15] Ehrman, M., Breathing Easier Ė Bad Breath Has Smell of Success:  The California Breath Clinics, Los Angeles Times, Sept. 16, 1994.

 

[16]  The Marketeer Business Magazine, A Breathtaking Breakthrough:  Dr. Harold Katz & The California Breath Clinics, October, 1995.  Cox Publications. Sacramento, CA.

 

[17] Hammer, J., Kaster, D., Scheele, R. The Role of Volatile Sulfur Gases on the Increased Permeability of the Periodontal Ligament Attachment Apparatus. Monograph. Presented at Symposium on Oral Malodor, Acapulco, Mexico, 1991.

 

 

 

 

[18] Richter, J., Diagnosis and Treatment of Halitosis. Compendium, April 1996. Vol 17. 4, 370-386.

 

[19] Interscan Corp., Chatsworth, CA.

20 Yaegaki, K, Sanada, K., Volatile Sulfur Compounds in mouth air from clinically healthy subjects and patients with Periodontal Disease.  Journal of Periodontal Res. 1992; 27, 233-238.

 

 

 

 

[21] Foster, R. D., Donít be a Foul Mouth Ė The latest treatments can banish bad breath forever.  Menís Fitness, July, 1998, p. 39-48.

 

[22] Masschelein, W.J., Rice, Rip, Editor, Chlorine Dioxide: Chemistry and Environmental Impact of Oxychlorine Compounds.  Ann Arbor Science Publishers, Inc.  Ann Arbor, MI.  1979.

 

[23] Engelhard Chemical. Chlorine Dioxide from Engelhard:  The safe, convenient, cost-effective alternative for disinfecting and deodorizing.  Iselin, N.J., November, 1997.

 

[24] Abdel-Rahman, Couri, D., Effect of chlorine dioxide and metabolites on glutathione dependent system in rat, mouse, and chicken blood.  Journal of Environmental Path Toxicology 1979; 3 (1,2): 451-60.

 

[25] Lubbers, J.R., Sudha, C, Miller, J, Bianchine, J.R., Chronic Chlorine Dioxide Intake in Man.  Chem-Orbital. 1994. 

 

[26] Khanna, N.  Monograph:  Pharmagene:  Advanced formulas of chlorine dioxide with latent precursors.  Bio-Cide International, 1999.

 

[27] Spindler, S.J., Spindler, G., Evaluation of a stabilized chlorine dioxide paste-rinse combination regimen vs. a pheno-related regimen.  Journal of Periodontology, January 1998.

 

[28] Lynch, E., Grootveld, C., Silkwood, C.  Ability of Oral Health Care Products to Alleviate Oral Malodour.  Dept. of Conservative Dentistry, St. Bartholomewís and the Royal London School of Medicine and Dentistry, London, 1996.

 

[29] Kwong, M., Effectiveness of a chlorine dioxide mouthrinse as a preprocedural rinse for the reduction of bacteria in dental office aerosols.  Medical College of Ohio, 1996.