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Dental Gum

Casein Phosphopeptide-Amorphous Calcium Phosphate and the
Remineralization of Enamel
a report by
Eric C Reynolds, AO

Professor of Dental Science and Head, School of Dental Science, The University of Melbourne

Casein phosphopeptide-amorphous calcium Reynolds and colleagues, using an in situ animal caries Eric C Reynolds, AO is Professor of
Dental Science and Head of the
phosphate (CPP-ACP) nanocomplexes are derived model, showed that exposure of enamel plaque to
School of Dental Science at The
from bovine milk protein, casein and calcium and solutions of tryptic peptides of casein significantly University of Melbourne. Professor
phosphate. The concept of CPP-ACP as a reduced enamel subsurface demineralization. Casein Reynolds is also Associate Dean of
the Faculty of Medicine, Dentistry
remineralizing agent was first postulated in 1998.1 A peptides were incorporated into enamel plaque and
and Health Sciences at The
number of subsequent studies have demonstrated were associated with increases in the plaque’s content University of Melbourne and Chief
CPP-ACP to have anticariogenic activity in of calcium and phosphate.The investigators concluded Executive Officer of the Cooperative
Research Centre for Oral Health
laboratory, animal, and human in situ experiments.2-4 that the tryptic peptides responsible for caseinate’s
Science. He has been researching
This has led to the incorporation of CPP-ACP into anticariogenic activity were the calcium phosphate- and teaching for over 20 years on
food products and dental products as a new tool in the stabilizing CPPs (casein phosphopeptides).1 These the etiology and prevention of oral
diseases. He has over 200 scientific
fight against caries. CPPs contain a specific sequence, which markedly
publications and 16 patents.
increases the apparent solubility of calcium phosphate Professor Reynolds is on the
CPP-ACP—A New Adjunctive Agent for by stabilizing ACP, forming solutions that are editorial board for the Australian
Dental Journal and has also been a
Caries Control supersaturated with respect to the calcium phosphates.
member of the editorial board for
the Journal of Dental Research. He
Caries initiation is associated with demineralization of In an animal caries study, a 0.5% weight per volume has received numerous awards and
distinctions, with the most
subsurface tooth enamel. Calcium and phosphate are (w/v) solution of CPP-ACP nanocomplexes was
significant being the Clunies Ross
lost from the subsurface enamel, resulting in the demonstrated to be comparable with a 500ppm National Science and Technology
formation of a subsurface lesion. At this early stage, the fluoride solution in reducing caries activity.10 CPP- Award in 2002 , which honours
those who make important
caries lesion is reversible via a remineralization process ACP solutions, applied twice daily to the teeth of
contributions to science for the
involving the diffusion of calcium and phosphate ions specific-pathogen-free rats orally infected with economic, social and environmental
into the subsurface lesion to restore lost structure. Since Streptococcus sobrinus, a bacterium that causes tooth decay benefit of Australia, and the Victoria
Prize in 2005, which is awarded to
several studies had demonstrated that milk-based in humans, significantly reduced caries activity, with
an individual whose scientific
products appeared to have anticariogenic properties in 0.1% w/v CPP-ACP producing a 14% reduction, and discovery or technological
animal models,5-8 attention was focused on identifying 1.0% w/v CPP-ACP producing a 55% reduction innovation has significantly
advanced the State of Victoria’s
the specific milk-based agents that were responsible for relative to the distilled water control. The
knowledge base and has potential
the ‘anticaries effect’. anticariogenicity of CPP-ACP and fluoride was to lead to a commercial outcome.
In 2005, he was appointed an
Officer of the Order of Australia
1. Reynolds EC,“Anticariogenic complexes of amorphous calcium phosphate stabilized by casein phosphopeptides: A review”, Spec
(AO) for service to community
Care Dentist (1998);8: pp. 8–16. dental health through research and
2. Reynolds EC, et al., “Advances in enamel remineralization: Anticariogenic casein phosphopeptide - amorphous calcium development of preventive and
restorative products, to dental
phosphate”, J Clin Dent (1999);10: pp. 86–88.
education through curriculum
3. Reynolds EC, et al.,“Retention in plaque and remineralization of enamel lesions by various forms of calcium in a mouthrinse or development, and as an
sugar-free chewing gum”, J Dent Res (2003);82: pp. 206–211. administrator and teacher.
4. Shen F, et al., “Remineralization of enamel subsurface lesions by sugar-free chewing gum containing casein phosphopeptide-
amorphous calcium phosphate”, J Dent Res (2001);80: pp. 2066–2070.
5. Reynolds EC, Black CL, “Confectionery composition and rat caries”, Caries Res (1987);21: pp. 538–545.
6. Navia JM, Lopez H,“Rat caries assay of reference foods and sugar-containing snacks”, J Dent Res (1983); 62: pp. 893–898.
7. Bowen WH, et al., “A method to assess cariogenic potential of food-stuffs”, J Am Dent Assoc (1980); 100: pp. 677–681.
8. Harper DS, et al., “Cariostatic evaluation of cheeses with diverse physical and compositional characteristics”, Caries Res
(1986);20: pp. 123–130.
9. Reynolds EC, et al.,“Anticariogenicity of calcium phosphate complexes of tryptic casein phosphopeptides in the rat”, J Dent Res
(1995)74: pp. 1272–1279.
10. Moller IJ, Poulsen S, “The effect of sorbitol containing chewing gum on the incidence of dental caries, plaque and gingivitis in
Danish schoolchildren”, Community Dent Oral Epidemiol (1973);1: pp. 58–67.

U S D E N T I S T RY 2 0 0 6 51

CPP-ACP produced a 51 ± enamel blocks. The enamel daily for 14 days. Reynolds EC..11. 1623–1626. 52 U S D E N T I S T RY 2 0 0 6 .to seven- maintain a state of supersaturation with respect to fold increase in salivary flow rate over the two-minute tooth enamel. respectively. four times daily. depressing demineralization. et al. enamel half-slabs inset containing subsurface demineralized lesions.. No alterations were made to the 19% reduction in enamel mineral loss caused by subjects’ diet and oral hygiene procedures for the frequent sugar-solution exposure. were worn for 40 minutes. which buffers the free calcium appropriate computerized imaging software. J Am Dent Assoc (1998). These results indicated that the gum on enamel remineralization was evaluated in addition of CPP-ACP to sugar-free chewing gum three randomized. No significant difference was enhancing remineralization.10 All subjects used standard fluoride dentifrice for the A human in situ caries model study evaluated the ability duration of each study and chewed the gums at their of a 1. J Dent Res (2003). crossover studies in significantly enhanced remineralization of enamel 30 patients. No be an excellent delivery vehicle for CPP-APP to significant correlation was found between individual remineralize enamel subsurface lesions. All chewing subjects. to prevent enamel demineralization. independent of gum weight or type. In the no-treatment control. J Dent Res (1990). and type (slab or pellet) of subsurface lesions in situ when delivered in a sugar-free gum. it was proposed that sugar-free gum may sugar-free gum not containing CPP-ACP. Gagnon G. Beiswanger BB. gum treatments were double-blinded and randomized.0.13 The mouthrinse study was a randomized. The addition of CPP-ACP to either the sorbitol. as animals receiving 0.129: pp. with a 63%.82(3): pp. cross-over design involving four coded 11. relative to the 13 Therefore. 12. Subjects were instructed daily use of the 1. CPP-ACP dose.1 duration of each study. Microradiographic ACP is the localization of calcium and phosphate ions analyses of the enamel lesions were evaluated using at the tooth surface.qxp 23/10/06 2:57 pm Page 52 Dental Gum additive. and 152% average increase. in fact. et al. The and phosphate ion activities. They recovered from the removable intraoral appliance used were informed not to brush the area containing the in the study. After completion of each treatment period.“A 24-month clinical study of the incidence and progression of dental caries in relation to consumption of chewing gum containing xylitol in school preventive programs”. double-blind. weight.5% CPP-ACP plus For each study. The twice. anticariogenic effect through the stimulation of saliva. the enamel blocks were removed The probable anticariogenic mechanism for CPP.or xylitol-based gums at 10. or 56.Reynolds_edit. Kandelman D.The appliances were worn for the 20 plaque that developed in this model was minutes of gum chewing and for 20 minutes bacteriologically similar to normal supragingival plaque following. thereby helping to chewing of sugar-free gum produced a four. with at least one week than those animals receiving either CPP-ACP or between treatments.0% CPP-ACP solution resulted in a not to eat or drink while wearing the appliance and to 144% increase in calcium level and a 160% increase in rinse and clean their appliances using the fluoride-free inorganic phosphate level in the interenamel plaque denture cleanser plate and toothbrush provided. Moreover. 1771–1775. unstimulated or stimulated salivary flow rates and percentage enamel remineralization values obtained for The effect of incorporating CPP-ACP into sugar-free any of the treatments. 206–211. twice natural chewing frequency for 20 minutes.4 The subjects in the studies wore subsurface lesions in a dose-related manner. removable palatal acrylic appliances with six human. 13. “The effect of chewing sugar-free gum after meals on clinical caries incidence”.“Retention in plaque and remineralization of enamel lesions by various forms of calcium in a mouthrinse or sugar-free chewing gum”.0% CPP-ACP solution as a mouthrinse.The gums were provided as coded products randomized. fluoride alone. all subjects crossed over to each 500ppm fluoride had significantly lower caries activity randomly assigned treatment. the appliances on frequent exposure to sucrose solutions. and period in all subjects. double-blind. can have an increase in enamel remineralization.001) that the gum is non-cariogenic and.4mg produced a significant (p>0.1-2 observed between the sorbitol-based and xylitol-based gums in their ability to stimulate saliva or remineralize CPP-ACP in Chewing Gum subsurface enamel lesions. Clinical trials of sugar-free chewing gum have shown 18. and number of mouthrinse or sugar-free gum was studied in treatments.69: pp. 102%. double-blind trials involving 30 adult and were stored at room temperature. from the appliances for processing. The protocols of the three The ability of CPP-ACP to be retained in studies were identical except for the specific sweetener supragingival plaque and remineralize enamel (sorbitol or xylitol).8.

not recommended for your patients with milk allergies.tridentgum.qxp 29/9/06 11:03 am Page 53 Right now. Receive 150 extra samples of Trident White ® (a $6 value) FREE with your first order. Reynolds EC. Shen P.Cadb_TriWhite_ad. ■ Clinical information on how Trident® gum can help your patients protect and whiten their teeth. they can whiten teeth in as little as 4 weeks. proven to remineralize enamel by delivering calcium and phosphate in soluble form to tooth surfaces. Vincent J. Remineralization of enamel subsurface lesions by sugar-free chewing gum containing casein phosphopeptide-amorphous calcium phosphate.2. ■ 100 samples of Trident White® and 150 single-serving samples of Trident® sugarless gum. Shen P. J Dent Res. 80: 2066-2070. 2. .1 Trident White® also contains Recaldent® (milk-derived ACP-CPP). Call 1-800-874-0013 to order a Trident ® Oral Care Starter Kit today. 2001. © 2006 Cadbury Adams USA LLC www. And when patients chew Trident White® for 20 minutes. 2003. Data on file. you'll receive: ■ 72 retail-sized. ■ Money-saving patient coupons. For just $19.99. RECALDENT is a registered trademark of Recaldent Pty. J Dent Res.com REFERENCES: 1. But Dan is chewing Trident White® gum. 82: 206-211. Allow 4-6 weeks for delivery. 5-stick packs of Trident® sugarless gum. Ltd. RECALDENT® is digestible by patients with lactose intolerance. Cai F. therefore. ■ FREE counter display and Trident ® patient newsletters. Reynolds EC. Retention in plaque and remineralization of enamel lesions by various forms of calcium in a mouthrinse or sugar-free chewing gum. Cai F. Dan is having his teeth whitened. 4 times a day. It’s not as good as the whitening you do. Order Your Trident ® Oral Care Starter Kit Today.3 That makes it a perfect addition to professional whitening. Walker GD. Nowicki A. 3. of course. RECALDENT® is milk derived and.

taken at the baseline and at the completion of the These results highlight the importance of CPP in clinical trial. Iijima Y.. the most calcium per piece of gum.4% and 88. respectively). Caries Res (2004). 15.“CPP-ACP gum slows progression and enhances regression of dental caries”.5% and 41. as well as to the intercellular plaque matrix. in adolescents.and 16-hour acid challenge of the continue to emerge in importance as fluoride did in the lesions remineralized with the control gum resulted in past for caries prevention and reduction. compared with the control gum.The level of remineralization 21st century. Morgan MV. The gum CPP-ACP-containing products to their patients. Moreover. although not containing group received an identical gum without CPP-ACP.. while for the CPP-ACP-remineralized lesions mouthrinse contained an unstabilized slurry of 60mM the corresponding reductions were 30. Standardized digital bitewing radiographs were subjects chewed the CPP-ACP-containing gum. The CPP-ACP gum slowed progression of superior to the other sugar-free gums in caries compared with the control gum.14 The study compared sugar-free gum Summary containing 18.001).The CPP-ACP gum also enhanced regression of caries In a recent double-blind. CaCl2 and 40mM sodium phosphate. According to the results. three times per day. with one session of gum-chewing frequency and duration. the enamel slabs were remineralization. ■ 14. two randomized. All subjects received conducted with three pellet and three slab sugar-free accepted preventive procedures and optimum systemic gums containing different forms of calcium. even percent more of the approximal surfaces experienced though the other gums contained from five to 13 caries progression in the control gum group compared times the level of total calcium. respectively. Analysis of caries progression or regression delivering ACP to the tooth surface. to the same surfaces in the CPP-ACP gum group. containing mouthrinses significantly increased plaque indicating that the remineralized mineral was more calcium and inorganic phosphate levels. There was a results also demonstrate the importance of the CPP in statistically significant difference in the distributions of stabilizing ACP and producing a highly water-soluble the transition scores between the two groups calcium phosphate phase.0% reductions. Remineralization of early carious lesions may gum.8mg of CPP-ACP and sugar-free gum not containing CPP-ACP.8%. the was undertaken using a transition matrix. Dental practitioners should recommend was determined using microradiography. The eight.qxp 23/10/06 2:58 pm Page 54 Dental Gum mouthrinses.Reynolds_edit. The incorporation of CPP-ACP chewed the gum for 20 minutes four times daily for 14 into chewing gum has been shown to increase enamel days.38(6): pp. Subjects wore removable The enamel remineralizing properties of CPP-ACP have palatal appliances with insets of human enamel been determined from many years of basic and evidence- containing demineralized subsurface lesions. the active treatment group control gum group. (2006) June 28 – July 1: Abstract 2445. CPP-ACP gum has also been shown to slow the progression and enhance the regression of dental caries In the chewing gum studies. 65. containing CPP-ACP produced approximately twice particularly children. After each treatment.4mg CPP-ACP. In the mouthrinse study. Nineteen remineralizing enamel subsurface lesions in situ. as well as adults who are at high risk the level of remineralization as the control sugar-free for caries.This represents a significant advance in removed and half of each lesion challenged with acid in treatment of early carious lesions and prevention in the vitro for eight or 16 hours. while the control containing the CPP-ACP. “Acid resistance of enamel subsurface lesions remineralized by a sugar-free chewing gum containing casein phosphopeptide-amorphous calcium phosphate”. of deposited ACP (2% w/v and 6% w/v. over the two-year study could be detected in plaque extracts three hours after period. et al. 84th IADR General Session and Exhibition. The CPP-ACP gums were (p<0. 54 U S D E N T I S T RY 2 0 0 6 . cross-over study.720 subjects were randomly assigned double-blind cross over remineralization trials were to either a test or control group. The fourth The acid challenge after in situ remineralization for mouthrinse was de-ionized water and acted as the both control and CPP-ACP-treated lesions resulted in control. randomized. demineralization underneath the remineralized zone. the gum gum containing 54. produced the Subjects were instructed to chew their assigned gum for highest level of enamel remineralization independent 10 minutes. and based clinical research. only the CPP-ACP. including fluoride exposure. 2.Two of the mouthrinses contained CPP. The CPP supervised on school days. The test group received a sugar-free CPP-ACP. 551–556. et al. and the CPP resistant to subsequent acid challenge. were immunolocalized to the surfaces of bacterial cells. the third mineral.15 demonstrated superior resistance to a subsequent acid challenge. Fifty-six percent more designed to investigate the acid resistance of enamel of the approximal surfaces experienced caries regression lesions remineralized in situ by a sugar-free chewing in the CPP-ACP gum group compared to those in the gum containing CPP-ACP.