Medical Treatment of Dental Caries With a New 25% Xylitol Formulation

Background
Even with the declining prevalence of dental caries in industrialized countries during the past decades, predominately due to fluoride use, 1 dental caries is still a major problem in most industrialized countries, affecting 60% to 90% of children, and the vast majority of adults. 2 Also, there is mounting international evidence that this decline is ending 3 and that many dental patients are still highly infected with cariogenic bacteria (105 Streptococcus mutans/mL of saliva).

Dental caries remains a significant health problem 4 and is still the predominant reason for tooth loss in almost all age groups. 5 Although dental caries is a largely preventable disease, untreated cavitated carious lesions in permanent teeth are still the most prevalent health condition globally. In primary teeth, it also a very common condition 6, with the possibility of many dental, medical, social, and quality of life sequalae. 7 At the same time, real effectiveness of curative and preventive approaches on high risk caries patients are being questioned in many countries. 8,9

Since 1952, sodium fluoride in toothpaste has been the most widely used therapeutic agent. It has the potential to remineralize, but might not change the patient’s caries risk and may not offer optimal removal of cariogenic bacteria. This is why, more than 12 years ago, I tried to identify a therapeutic agent able to control the disease and reduce the cariogenic bacteria load. I conducted many studies, the most significant being with 202 Kosovar children, to confirm the efficacy of a new 25% xylitol toothpaste formulation. This therapeutic concentration was tested as an antibacterial agent to reduce the cariogenic bacteria load and as a therapeutic agent to prevent cavitated and non-cavitated carious lesions and as a remineralizer. The present paper presents the results of this research, and the development of the new X-PUR CariØ toothpaste with 25% xylitol.

The Idea Behind the New 25% Xylitol Toothpaste Formulation

Current Treatment Strategies
Many authors suggested medical strategies aimed at controlling cariogenic bacteria colonization instead of conventional approaches. 10 The Tanzer et al. review 11 identified that the main pathogenic bacteria involved in the caries process are Streptococcus mutans (SM) and Lactobacilli (L). SM/L are seen 12 as a prerequisite for the caries process and their increase is responsible for the pathological shift within the caries biofilm. Clinical key threshold of SM/L contamination for critical pathological shift is ≥ 105/ml of saliva. 13,14 Modern caries antibacterial treatments such as toothpastes, oral rinses and others vehicles should always be tested to convert infection level under this 105 threshold (Table 1).

Specifically, SM are associated with dental tissue destruction in rampant lesions 15 to caries lesions prevalence in children 16 in adolescents, 17 in adult 18 and in the elderly. 19

This SM association has been also documented for caries incidence 20 in early childhood, 21 among children 22 attending primary or secondary schools, 23 in young adults, 24 in adults 25 and in the elderly 26 and in lesions progression. 27-29 The presence of cariogenic bacteria has also been used successfully as a marker in risk assessment for any age, 29,30 as well as in monitoring the outcome of caries prevention. 11 In the end, cariogenic bacteria prevalence seems to affect the real efficacy of topical fluorides. 31

Table 1

Limitations of Sodium Fluoride Toothpastes
Unfortunately for patients, most dental products such as sodium fluoride toothpastes do not change the patient’s caries risk. They intervene at the end of the caries process, trying to minimize tissue damage. This is termed: tertiary prevention. Fluoride toothpaste does not create significant antibacterial – conversion under the key threshold on cariogenic bacteria in high caries risk individuals. Primary prevention action on the caries process is needed to change the patient’s caries risk.

Mechanism of Xylitol Action on Dental Caries
Xylitol was discovered in 1890 by Fisher and Stahe in Germany as a sugar-alcohol and later used as natural sugar substitute during WWII in Finland. 35 It is produced naturally in the human body (between five to fifteen grams of daily production). On a commercial scale, xylitol can be produced by chemical and biotechnological processes mainly from birch trees or corn cobs. 36 Industrial xylitol production reproduces the same molecular structure of the natural one. 37 Two main hypotheses explain the bacterial effect of xylitol on the caries process 39: either by a chewing 38 movement, related to xylitol, producing saliva or as a sweetener substitute which is essentially not fermentable by the caries-inductive oral microflora. 40 Xylitol’s principal mechanism is in its early action in the caries process and thereby, in the prevention of carious lesions 40 (Fig. 1).

Fig. 1

Xylitol as an Antibacterial Agent
Chewing gum has been the most tested vehicle for xylitol delivery in clinical studies. 41 Several clinical trials 42-45 and literature reviews 46-51 have confirmed the potential of xylitol to reduce cariogenic bacteria using chewing gum. 52 This evidence has allowed Health Canada to officially recognize xylitol gums as an antibacterial agent on cariogenic bacteria, and also as a saliva stimulating agent. 53

Xylitol as a Therapeutic Agent
As a therapeutic agent, systematic xylitol use leads to impressive reductions in caries incidence. 54 This has been reported by many researchers 55,56 and in literature review. 57,58 With chewing gum, several studies show carious lesion reduction among children after exposure of 12 to 40 months 44,47,48,59-61 and systematic reviews reported some high preventive fractions on caries experiences. 44,62 Therapeutic effects were estimated from xylitol trials using menthols, candies, 52,63 syrup (8 grams/day), 64 wipes 65 and milk 66 with success. An observational study showed effectiveness of xylitol gum-lozenges on root caries lesions. 67 In 1990, two trials used toothpaste as a vehicle for xylitol 10% (0.1 g/tooth brushing). One trial combined it to NaF 68 and in the other, Sodium of Monofluorophaste 69 using a total of 4 800 school children and reported a negligible prevention fraction of 10 % and 13% respectively. The authors concluded that xylitol in toothpaste might be irrelevant.

The Study
Worldwide, the most convenient vehicle for personal hygiene and compliance of active agent, is toothpaste. 70 Natural toothpaste containing 25% of xylitol has been tested as an antibacterial and therapeutic agent on cariogenic bacteria in Eastern Europe. Study sites we selected primarily as vulnerable territories for caries prevalence by the author. Pristina in Kosovo and Cluj in Romania, respected these criteria. 71 Begzati et al. 71-73 established, for example, that SM prevalence was 98% in ECC (Early Childhood Caries) children of Pristina and the prevalence of carious lesions in children aged two to six years was 91.2%. In Kosovo, 72% of adults 74 were affected by caries experiences. 75 In Romania, among 548 six to eight-year-olds, 84.3% had caries experience.

The following are the results of the study:

• 25% Xylitol Toothpaste to Reduce Cariogenic Bacteria Load: The patients were exposed to twice daily tooth brushing with the 25% xylitol formula. The results showed that the 25% xylitol toothpaste was more effective than a sodium fluoride toothpaste in reducing cariogenic bacteria load 76,77 (Table 2).
• 25% Xylitol Toothpaste to Reduce Non-Cavitated Lesions, Cavitated Lesions and to Remineralize: The results showed that the 25% xylitol toothpaste was more effective than a sodium fluoride toothpaste in reducing non-cavitated lesions, cavitated lesions and in remineralization 78 (Table 3).
• X-PUR CARIØ, a New Fluoride Free Toothpaste with 25% Xylitol: In Canada, a new fluoride-free toothpaste containing 25% xylitol as the medicinal ingredient will be available for dental professionals and patients by the end of 2018 under the name X-PUR CariØ (Oral Science, Brossard, Quebec) (Fig. 2).

Table 2

Table 3

Fig. 2

Conclusion
According to recent stats, the prevalence of caries in at-risk individuals increased between 1994 and 2012, despite exposure to various fluoride products. As well, patients are increasingly drawn to and are buying natural dental products even though they contain no therapeutic agents. This is contributing to a rise in carious lesions. This is the rationale behind the development and introduction of an effective caries reducing natural toothpaste containing 25% concentrated xylitol as the sole anti-caries therapeutic and anti-bacterial agent. OH

Oral Health welcomes this original article.

References

1. Bratthall D., Hansel-Pettersson G., and Sundberg H., Reasons for the caries decline : what do the experts believe ? European Journal of Oral Sciences, 1996. 104: p. 416-422.
2. Petersen P.E., The world oral health report 2003: continuous improvement of oral health in the 21st century–the approch of the who global oral health programme. Community Dentistry and Oral Epidemiology, 2003. 3(supp. 1): p. 3-24.
3. Speechley M., J.D., Some Evidence from Ontario, Canada, of a Reversal in the Dental Caries Decline. Caries Res, 1996. 30(6): p. 423-7.
4. Koch G., H.A.N., Ullbro C., Caries prevalence and distribution in individuals aged 3-20 years in Jönköping, Sweden: trends over 40 years. Eur Arch Paediatr Dent, 2017 Oct. 18(5): p. 363-370.
5. Fejerskov O., Strategies in the design of preventive programs. Adv Dent Res, 1995. 9(2): p. 82-88.
6. Kassebaum N.J., B.E., Dahiya M., Global burden of untreated caries: a systematic review and metaregression. J Dent Res, 2015. 94(1): p. 1-9.
7. Fontana M., The clinical, environmental, and behavioral factors that foster early childhood caries. Pediatr Dent., 2015 May-June. 37(3): p. 217-25.
8. Fejerskov O., Strategies in the Design of Preventive Programs. Adv Dent Res., 1995. 9: p. 82-88.
9. Splieth C.H., N.A.W., König K.G., Caries prevention programs for groups: out of fashion or up to date? Clin Oral Investig., 2004. 8(1): p. 6-10.
10. Köhler B., A.I., Mutans Streptococci and Caries Prevalence in Children after Early Maternal Caries Prevention: A Follow-Up at 19 Years of Age Caries Res, 2012. 12(46): p. 474-480.
11. Tanzer J.M., Livingston J., and Thompson A.M., The Microbiology of Primary Dental Caries in Humans. Journal of Dental Education, 2001. 65: p. 1028-1037.
12. Ruby J.D., G.M., Hargreaves J.A., Streptococcus mutans, an assessment of its physiological potential in relation to dental caries. Rev Can Biol., 1978. 37(4): p. 273-89.
13. Begzati A., B.M., Meqa K., Early childhood caries in preschool children of Kosovo–a serious public health problem. BMC Public Health., 2010. 10(788): p. 1-8.
14. Brambilla E., et al., Caries-Preventive Effect of Topical Amine Fluoride in Children with High and Low Salivary Levels of Mutans Steptococci. Caries Research, 1999. 33: p. 423-427.
15. Berkowitz R., Etiology of Nursing Caries: a Microbiologic Perspective. Journal of Public Health Dentistry, 1996. 56(1): p. 51-54.
16. Saraithong P., P.K., Chen Z., Khongkhunthian S., Laohapensang P., Chhun N., Pattanaporn W., Gaw H.Y., Li Y., Streptococcus mutans and Streptococcus sobrinus colonization and caries experience in 3- and 5-year-old Thai children. Clin Oral Investig., 2015. 19(8): p. 1955-64.
17. Relvas M., C.C., Velazco Henriques C., Ramos E.. Cariogenic bacteria and dental health status in adolescents: the role of oral health behaviours. Eur J Paediatr Dent. , 2014. 15(3): p. 281-7.
18. Apostolska S., R.V., Ivanovski K., Peeva M., Elencevski S., Presence of caries with different levels of oral hygiene. Prilozi, 2011. 32(1): p. 269-81.
19. MacEntee M., C.D.C., Glick N., Predictors of caries in old age. Gerodontology. 10(2).
20. Milgrom P., et al., Dental caries and its relationship to bacterial infection, hypoplasia, diet, and oral hygiene in 6- to 36-month-old children. Community Dent Oral Epidemiol, 2000. 28(4): p. 295-306.
21. Bankel M., R.A., Köhler B., Carious lesions and caries risk predictors in a group of Swedish children 2 to 3 years of age. One year observation. Eur J Paediatr Dent., 2011. 12(4): p. 215-9.
22. Wennhall I., M.L., Twetman S., Salivary mutans streptococci in 6-year-old children from a multicultural suburban area after attending an oral health program. Eur Arch Paediatr Dent., 2008. 9(2): p. 94-7.
23. Hong X., H.D.Y., Salivary Streptococcus mutans level: value in caries prediction for 11-12-year-old children. Community Dent Health. , 2010. 27(4): p. 248-52.
24. B., K., Long-term effect of intensive caries prophylaxis. Community Dent Oral Epidemiol., 1984. 12(2): p. 69-71.
25. S., F., Five-year incidence of caries, salivary and microbial conditions in 60-, 70- and 80-year-old Swedish individuals. Caries Res., 1998. 32(3): p. 166-74.
26. MacEntee M.I., C.D.C., Glick N., Predictors of caries in old age. Gerodontology., 1993. 10(2): p. 1993 Dec.
27. Grindefjord M., Dahllof G., and Modeer T., Caries development in children form 2.5 to 3.5 years of age: a longitudinal study. Caries Res., 1995. 29: p. 449-54.
28. Kristoffersson K., G.H.G., Bratthall D., The more Streptococcus mutans, the more caries on approximal surfaces. J Dent Res. , 1985. 64(1): p. 58-61.
29. G.H., P., Assessing caries risk—using the Cariogram model. Swed Dent J. Suppl., 2003. 158: p. 1-65.
30. Thenisch N.L., B.L.M., Imfeld T., Leisebach Minder T., Steurer J., Are mutans streptococci detected in preschool children a reliable predictive factor for dental caries risk? A systematic review. Caries Res., 2006. 40(5): p. 366-74.
31. Brambilla E., et al., Caries-preventive effect of topical amine fluoride in children with high and low salivary levels of mutans streptococci. Caries Res., 1999. 33: p. 423-7.
32. Kidd E.A.M., Essentials of dental caries. 2005, New-York: Oxford university press. 180 pages.
33. Fejerskov O., Concepts of dental caries and their consequences for understanding the disease. Community dent and Oral Epidemiology, 1997. 25(1): p. 5-12.
34. Faustova M.O., A.M.M., Basarab Y.O., Dobrobolska O.V., Vovk I.M., Loban’ G.A., Bacterial factors of cariogenicity (literature review). Wiad Lek, 2018. 71((2 pt 2)): p. 378-382.
35. Bar A., Caries prevention with xylitol. A review of the scientific evidence. . World Rev Nutr Diet. , 1988. 55: p. 183-209.
36. Ur-Rehman S., M.Z., Zahoor T., Jamil A., Murtaza M.A., Xylitol: a review on bioproduction, application, health benefits, and related safety issues. Crit Rev Food Sci Nutr., 2015. 55(11): p. 1514-28.
37. Lif Holgerson P., Ö.C., Rönnlund A., Johansson I., Xylitol and its effects on oral ecology–clinical studies in children and adolescents. Department of Odontolgy, ed. U. University. 2007, Umea.
38. Mickenautsch S., L.S.C., Yengopal V., Anticariogenic effect of xylitol versus fluoride–a quantitative systematic review of clinical trials. Int Dent J., 2012. 62(1): p. 6-20.
39. S., K., Historical review of remineralization research. Journal of Clinical Dentistry, 1999. 10(2): p. 56-64.
40. Trahan L., Xylitol : a review of its action on mutans steptococci and dental plaque-its clinical significance. Int Dent J, 1995. 45: p. 77-92.
41. Ly K.A., M.P., Rothen M., The potential of dentalprotective chewing gum in oral health interventions. . Am Dent Assoc, 2008. 139(5): p. 553-63.
42. Söderling E., E.M., Honkala E., Fontana M., Flannagan S., Eckert G., Kokaras A., Paster B., Tolvanen M., Honkala S., Effects of short-term xylitol gum chewing on the oral microbiome. Clin Oral Investig. , 2015. 19(2): p. 237-44.
43. J.M., T., Xylitol chewing gum and dental caries. Int Dent J, 1995. 45(supplement 1): p. 65-76.
44. Makinen K.K., B.C.A., Hujoel P.P., et al., Xylitol chewing gums and caries rates: a 40 month cohort study. J Dent Res, 1995. 74: p. 1904-1913.
45. Makinen K.K., K.P.I.K.P., Kivilompolo T., Pirkko-Liisa Makinen P.L., Satu Murtomaa S., Juhani Petaja J., ukka ToivanenU., Eva Soderling E., The effect of polyol-combinant saliva stimulants on S. mutans levels in plaque and saliva of patients with mental retardation Spec Care Dentist 2002. 22(5): p. 187-193.
46. K.K., M., Latest dental sutdies on xylitol and mechanism of action of xylitol in caries limitation, in Progress in sweeteners, G. T, Editor. 1989, Elsevier: London. p. 331-362.
47. Teixeira A.K., R.A.G., Noro L.R., The impact of polyol-containing chewing gums on dental caries: a systematic review of original randomized controlled trials and observational studies. J of the American Dental Association, 2008. 139(12): p. 1602-1614.
48. Isokangas P., A.P., Tiekso J., et al., Xylitol chewing gum in caries prevention: a field study in children. JADA, 1988. 117: p. 315-320.
49. Scheie A.A., F.O.B., Xylitol in caries prevention: What is the evidence for clinical efficacy? Oral Dis., 1998. 4: p. 268-278.
50. Milgrom, P., K.A. L.., Rothen M., Research Findings on Xylitol and the Development of Xylitol Vehicles to Address Public Health Needs. Caries Res., 2009. 43(6): p. 455-61.
51. Milgrom P., L.K.A., Roberts M.C., Rothen M., Mueller G., Yamaguchi D.K., Mutans streptococci dose response to xylitol chewing gum. J.Dent.Res., 2006. 85(2): p. 177-81.
52. Honkala E., R.A., Karvoren S. et al., Chewing of xylitol gum – A well adopted practice among Finnish Adolescents. Caries Res., 1996. 30: p. 34-39.
53. Hanno A.G., A.N.M., Almushayt A.S., Masoud M.I., Sabbagh H.J., Farsi N.M., Effect of xylitol on dental caries and salivary Streptococcus mutans levels among a group of mother-child pairs. J Clin Pediatr Dent. , 2011. 36(1): p. 25-30.
54. Peldyak J., M.K.K., Xylitol for caries prevention. J Dent Hyg., 2002 Fall. 76(4): p. 276-85.
55. Anonymous, Xylitol-containing oral syrup may prevent caries in children. The Journal of the American Dental Association, 2009. 140: p. p. 972.
56. Anonymous, Xylitol cleared for anti-caries health claims. Br Dent J., 2009. 206(3): p. p. 123.
57. S., T., Consistent evidence to support the use of xylitol- and sorbitol–containing chewing gum to prevent dental caries. J of Evidence-Based Dental, 2009. 10: p. 10-11.
58. B.L., E., Solving the problem of early childhood caries: a challenge for us all. Archives of Pediatrics and Adolescents, 2009. 163(7): p. 667-668.
59. Isokangas P., A.P., Tiekso J., et al., Long-term effect of xylitol chewing gum on dental caries. Community Dent Oral Epidemiol., 1989. 17: p. 200-3.
60. Kandelman D., Gagnon G., and Clinical Results After 12 Months from a Study of the Incidence and Progression of Dental Caries in Relation to Consumption of Chewing-gum Containing Xylitol in School Preventive Programs. J Dent Res., 1987. 66: p. 1407-1411.
61. Kandelman D., B.A., Hefti A., Collaborative WHO xylitol field study in French Polynesia. I Baseline prevalence and 32-month caries increment. Caries Res., 1988. 22: p. 55-62.
62. Mickenautsch S., L.S.C., Yengopal V., Bezerra A.C., Crucivel V., Sugar-free chewing gum and dental caries — a systematic review. Journal of Applied Oral Science, 2007. 15(2): p. 83-88.
63. Alanen P., Isokangas P., and G. K., Xylitol condies in caires prevention: results of a field study in Estonian children. Community Dent Oral Epidemiol, 2000. 28(3): p. 218-24.
64. Milgrom P., L.K.A., Tut O.K., Mancl L., Roberts M.C., Briand K., Gancio M.J., Xylitol pediatric topical oral syrup to prevent dental caries: a double-blind randomized clinical trial of efficacy. Arch Pediatr Adolesc Med. , 2009. 163(7): p. 601-7.
65. Zhan L., C.J., Chang P., Ngo M., Denbesten P.K., Hoover C.I., Featherstone J.D., Effects of xylitol wipes on cariogenic bacteria and caries in young children. J Dent Res. , 2012. 91(7 Suppl): p. 85S-90S.
66. K., M., The impact of milk with xylitol on dental caries : a review. J Pharm Sci Res. , 2013. 5(9): p. 178-180.
67. Ritter A.V., B.J.D., Leo M.C., Preisser J.S., Shugars D.A., Vollmer W.M., Amaechi B.T., Holland J.C., Tooth-surface-specific effects of xylitol: randomized trial results. J Dent Res, 2013. 92(6): p. 512-7.
68. Sintes J.L., E.C., Stewart B., McCool J.J., Garcia L., Volpe A.R., Triol C., Enhanced anticaries efficacy of a 0.243% sodium fluoride/10 % xylitol/silica dentifrice: 3-year clinical results. Am J Dent., 1995. 8(5): p. 231-5.
69. Sintes J.L., E.-B.A., Stewart B., Volpe A.R., Lovett J., Anticaries efficacy of sodium monofluorophosphate dentifrice containing xylitol in a dicalcium phosphate dehydrate base. A 30-month caries clinical study in Costa Rica. Am J Dent 2002. 15(4): p. 215-9.
70. Amaechi B.T., v.L.C., Fluorides and Non-Fluoride Remineralization Systems, in Toothpastes, v.L. C., Editor. 2013, Kager: Basel. p. 14-26.
71. Begzati A., M.K., Siegenthalerc D., Berishad M., Mautsche W., Dental Health Evaluation of Children in Kosovo. Eur J Dent, 2011. 5: p. 32-39.
72. Begzati A., B.A., Mega K.,Latifi-Xhemajli B.,Berisha M., Mother’s behaviours and knowledge related to caries experience of their children. Oral Health Prev Dent., 2014. 12(2): p. 133-40.
73. Begzati A., B.M., Meqa K., Early childhood caries in preschool children of Kosovo–a serious public health problem. BMC Public Health, 2010. 10(788): p. 1-8.
74. Kamberi B., K.F., Begzati A., Kelmendi J., Ilijazi D., Berisha N., Kqiku L., Prevalence of Dental Caries in Kosovar Adult Population. Int Dent J., 2016 Jul 19. 16.
75. Baciu D., D.I., Balcos C., Gallagher J.E., Bernabé E., Caries experience among Romanian schoolchildren: prevalence and trends 1992-2011. Community Dent Health., 2015 June. 32(2): p. 93-7.
76. Latifi-Xhemajli B., Clinical research on effectivness of Fluoride and Xylitol in preventing caries in early childhood-Longitudinal study, in Faculty of Medicine Dentistry Branch. 2016, University of Phristina Hasan Prishtina: Kosovo. p. 160.
77. Chi I., V.J.E., Badea M., OBSERVATIONAL DESIGN DOCUMENTING THE MINIMAL AND SUSTAINABLE TIMEFRAME FOR AN ANTIBACTERIAL EFFECTS OF XYLITOL 25 % TOOTHPASTE. 2017, Cluj University, Dental Faculty: Cluj Romania. p. To come.
78. Veronneau J., L.-X.B., Begzati A., Bytyci A., Kutlovci T., Rexhepi A., Effectiveness of xylitol toothpaste to decrease cariogenic bacteria among adults within 3-month period. not published yet, 2016.
79. Soderling E., I.P., Pienihakkinen K., Tenovuo J., Alanen P., Influence of maternal xylitol consumption on mother-child transmission of mutans streptococci: 6-year follow-up. 2001. 35(3): p. 173-7. 85. Véronneau & al., 2016.

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About the Author
Dr. Jacques Véronneau is a cariologist, researcher and speaker, working in private practice at Centres Dentaires Véronneau. He is a graduate of Montreal (DMD, MSc) and McGill (PhD) Universities and has done dental research on three continents. He has spent the last 12 years researching a more effective agent in reducing carious lesions and the cariogenic bacteria load.

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