Crossover Clinical Investigation of a Whitening Chewing Gum for Inhibiting Dental Stain Formation in Conjunction with Tooth Brushing

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1 Crossover Clinical Investigation of a Whitening Chewing Gum for Inhibiting Dental Stain Formation in Conjunction with Tooth Brushing Jeffery L. Milleman, DDS, MPA Kimberly R. Milleman, RDH, BS, MSEd Salus Research, Inc. Fort Wayne, IN, USA Carl J. Kleber, MSD, PhD University Park Research Center, Inc. Fort Wayne, IN, USA Howard M. Proskin, PhD Howard M. Proskin & Associates Rochester, NY, USA Michael Dodds, PhD Michael Kelley, PhD, RD Lilian Ramirez, BS Wm. Wrigley Jr. Co. Chicago, IL, USA Abstract Objective: The purpose of this clinical investigation was to evaluate the effectiveness of a marketed whitening chewing gum compared to a no-gum control in preventing the formation of extrinsic stains on the teeth of stain-forming subjects when chewed over a 12-week period of regular unsupervised use in conjunction with daily tooth brushing. Methods: This was a single-center, examiner-blind, randomized, 12-week crossover clinical trial. Stain-forming (after smoking or drinking coffee or tea) adults, starting with a stain-free baseline, either chewed the test gum (Orbit White) unsupervised four times per day, 15 minutes/chew, or used no gum along with daily brushing with a commercially available toothbrush and dentifrice for 12 weeks. At the crossover, all procedures were repeated with subjects assigned the opposite treatment. Extrinsic stain was measured at six and 12 weeks by both the Lobene Stain Index (LSI) and the Modified Lobene Stain Index (MLSI) using separate experienced examiners. Results: After 12 weeks, LSI stain scores showed a significant 25% reduction (p = ) in new stain formation for subjects using the test chewing gum along with tooth brushing versus tooth brushing alone (no-gum control). The corresponding MLSI stain scores demonstrated a 36% reduction (p < ) in the formation of extrinsic stain on the teeth. Conclusion: The overall findings of this clinical study demonstrated that regular use of Orbit White chewing gum, soon after smoking or drinking coffee or tea, will supplement daily tooth brushing in preventing unsightly stains from forming on the anterior teeth compared to brushing alone. (J Clin Dent 2014;25:37 42) Introduction The majority of people worldwide consider clean white teeth to be esthetically desirable. Teeth blemished with extrinsic stains are objectionable, both on the basis of cosmetic appearance and also socially as an indication of poor oral hygiene. Since the acquired pellicle, which coats the teeth, has a natural tendency to stain, most people will form some unsightly extrinsic stains on their teeth over time. This staining process is promoted by: 1) the ingestion of chromogenic foods and beverages such as coffee, tea, or red wine; 2) the use of tobacco products; and 3) exposure to certain cationic substances, such as tin, iron, and chlorhexidine. i Currently, the most widely practiced method for the control of extrinsic stains is daily tooth brushing with dentifrices. However, tooth brushing alone is not capable of completely preventing stain formation, and many people periodically need to have their teeth professionally cleaned. 37 A recent review has documented the oral health benefits of chewing gum, which include: neutralization of plaque acids; enamel remineralization; increased salivary flow; and removal of food debris, dental plaque, and tooth surface stains. ii With regard to the removal of existing dental stains, clinical studies have shown that a baking soda chewing gum was capable of removing extrinsic stains from the teeth when used as an adjunct to tooth brushing. 3-5 However, these studies compared the effect of the baking soda gums versus baseline stain and not versus a placebo control gum, which suggests that the effect may have been due, at least in part, to the chewing gum vehicle. In fact, a chewing gum without active ingredients was found to remove 48% of the natural stain (compared to baseline) from the anterior teeth of subjects who chewed the gum for 15 minutes after breakfast, lunch, and dinner for four weeks in conjunction with

2 38 The Journal of Clinical Dentistry Vol. XXV, No. 3 twice-daily tooth brushing for one minute. 6 With regard to inhibiting the formation of new stains on the teeth, a chewing gum without active ingredients was found to reduce the formation of the extrinsic dental stain caused by the daily use of a chlorhexidine mouthrinse in a six-week study. 7 In two studies using a two-day forced-stain model with chlorhexidine and no tooth brushing, a chewing gum containing sodium hexametaphosphate was found to significantly improve the whiteness of teeth compared to a placebo gum. 8,9 However, the placebo gum was also found to be effective in whitening the teeth compared to a no-gum control. All the above studies used chlorhexidine rinses to promote stain formation, and little has been done to examine the ability of chewing gum to actually inhibit the formation of natural stains. One study, using natural stain-forming subjects, found that a baking soda/pyrophosphate chewing gum, used twice daily in conjunction with once-daily tooth brushing, significantly reduced extrinsic stain formation compared to a breath mint (i.e., no gum) control after four and eight weeks of treatment. 10 The objective of the present clinical investigation was to determine the ability of a marketed tooth whitening chewing gum to prevent new stains from forming on the teeth of natural stainforming subjects who chewed the gum in addition to daily tooth brushing. Materials and Methods Study Design This clinical study was a single-site, randomized, examiner-blind, 12-week, two-period crossover design investigating the reduction in new extrinsic dental stain formation on the anterior teeth of stainforming adults (coffee, tea, or tobacco users) who used a marketed whitening chewing gum (Orbit White, Wm. Wrigley Jr. Co., Chicago, IL, USA) along with daily tooth brushing compared to brushing alone (i.e., a no-gum control group). Prior to the study, approval of the protocol and a subject consent form were obtained from an independent Institutional Review Board (U.S. Investigational Review Board, Miami, FL, USA). Subjects who regularly consumed coffee or tea or smoked tobacco products, and had a known history of extrinsic stain formation, were recruited for this study. Consenting subjects first completed a detailed medical/dental history and were screened in order to determine their acceptability for the study. A total of 76 subjects, consisting of approximately one-third each of daily coffee, tea, and tobacco users, and meeting the inclusion/exclusion criteria were accepted for the study. Participants were required to be at least 18 years of age, in good health, have a minimum of 11 natural anterior teeth with scoreable facial and lingual surfaces, and exhibit some extrinsic stain on their teeth. Subjects who never used chewing gum or had TMJ problems were excluded. Also, females self-reporting pregnancy or lactation were not enrolled. At the baseline examination for the first period of the crossover, subjects were assessed for oral soft/hard tissue health and then had their anterior teeth professionally cleaned to remove all existing extrinsic stains, thereby providing a stain-free baseline. A total of 76 subjects were randomized into two test groups. One group was provided the test chewing gum and instructed to chew two pellets (1.5 grams each) four times for 15 minutes each day, preferably after consumption of coffee, tea, or tobacco products. The test gum contained a peppermint flavor and conventional food-grade ingredients with no claimed active agents. The gum was supplied in white, unlabeled packaging with ten gum pellets per pack. Subjects were instructed to use a new pack daily, which provided two extra pellets per day in case of accidental loss, dropping a piece on the ground, etc. The second group, which served as the control, was given no gum and instructed not to chew any gum during the trial period. Both groups were also provided with a pre-weighed tube of commercial dentifrice (Colgate Regular, Colgate-Palmolive, New York, NY, USA), a soft toothbrush (Oral-B Indicator, Procter & Gamble, Cincinnati, OH, USA), and instructed to brush their teeth once daily in the morning. The first-time use of the products was supervised with verbal instructions, but all other treatments were unsupervised. Subjects were also provided with written treatment instructions and were required to maintain a diary of their chewing gum and/or tooth brushing treatments. In order to assess compliance, the amount of chewing gum and dentifrice used by the subjects was measured. During the trial period, subjects followed their usual dietary and tobacco habits, but they were not allowed to use any unassigned oral care, tooth whitening or chewing gum products, or have their teeth professionally cleaned or whitened. Subjects were instructed not to discuss their treatment products with any clinical personnel in order to maintain examiner blindness. After using their test products for a total of six and 12 weeks (± three days), subjects retuned to the clinic, were examined for oral health, and then assessed for extrinsic stain by two independent experienced examiners. One examiner used the Lobene Stain Index (LSI) 11,12 while the other examiner employed the Modified Lobene Stain Index (MLSI). 13,14 The examiners were also checked for repeatability by requiring both examiners to randomly re-score one subject in the morning and anther in the afternoon during examination days. After the final 12-week examination, the participants returned all remaining test products, were paid a gratuity, and their anterior teeth were again professionally cleaned to provide a new stain-free baseline. After a one-week washout period, the subjects repeated the entire study (second period of the crossover), except they participated in the opposite treatment group. A full description of the safety and clinical efficacy assessments follows. Oral Soft and Hard Tissue Health In order to evaluate test product safety, a visual and tactile inspection of the oral soft and hard tissues was performed at each examination using a standard dental light and mouth mirror. The tissues examined included the teeth, gingivae, palate, mucosa, tongue, lips, and perioral area. Any abnormalities were recorded, assessed for severity, and a judgment made for those not present at baseline as to whether they were potentially attributable to the test products. Lobene Stain Index The first experienced examiner scored the buccal and lingual surfaces of the anterior teeth using the standard LSI. Using this

3 Vol. XXV, No. 3 The Journal of Clinical Dentistry 39 index, each surface is divided into two segments: 1) the gingival region, comprised of a 3 mm-wide strip parallel to the gingival margin with the tip of the papillae designating the upper limit; and 2) the body region, comprising the central area of the tooth surface between the gingival region and extending to the incisal edge. Both regions were scored for area and severity according to the criteria in Figure 1. AREA INTENSITY 0 = no stain present, natural tooth color 0 = no stain 1 = stain covering up to 1/3 of the region 1 = light stain 2 = stain covering >1/3 to 2/3 of the region 2 = moderate stain 3 = stain covering >2/3 of the region 3 = heavy stain Figure 1. LSI scoring criteria for both the gingival and body regions of tooth surface. Modified Lobene Stain Index The second experienced examiner scored the buccal and lingual surfaces of the anterior teeth using a modification of the LSI. Using this index, each surface is divided into four segments: 1) the gingival region comprised of a 2 mm-wide strip parallel to the gingival margin between the mesial and distal line angles with the tip of the papillae designating the upper limit; 2) the mesial region comprised of the visible area between the mesial line angle and adjacent tooth, ending at the papilla (i.e., the start of the gingival region); 3) the distal region comprised of the visible area between the distal line angle and adjacent tooth, ending at the papilla; and 4) the body region comprising the central area of the tooth surface between the gingival and distal/mesial regions, extending to the incisal edge. All four regions were scored for area and severity according to the criteria summarized in Figure 2. Gingival/Mesial/Distal Region 0 = no stain present, natural tooth color 1 = thin line of stain, may be discontinuous 2 = thick line or band of stain 3 = stain covers entire area AREA Body Region 0 = no stain present, natural tooth color 1 = stain limited to pits and grooves 2 = stain outside pits/grooves < 10% 3 = stain outside pits/grooves > 10% INTENSITY All Regions 0 = no stain 1 = light stain 2 = moderate stain 3 = heavy stain Figure 2. MLSI scoring criteria for the gingival, mesial, distal, and body regions of tooth surface. For each scoring index, the mean stain score per subject was determined by multiplying the individual area and intensity scores from each region, summing them, and then dividing by the number of sites scored. Statistical Analysis The raw data were submitted to a statistical consultant for data management and statistical analyses. All cases were checked for compliance with the study protocol, and for accuracy and completeness. The cases which did not meet these requirements were excluded from primary analyses. Clinical stain scores were summed and averaged to provide mean per-subject scores at each clinical exam. The primary efficacy variables were the final 12-week clinical extrinsic stain scores. The parameters analyzed in this study were stain area, stain intensity, and stain product (calculated from the site-wise products of the area and intensity scores). For each of these, subject-wise whole mouth scores were evaluated for each study visit by taking the mean score over all sites measured in the mouth. Additionally, subject-wise mean scores were also calculated for the facial and lingual subsets of the mouth. For each study parameter, summary statistics (means and standard deviations) were calculated for each study visit. The data from this crossover study were analyzed using a linear model, which included the fixed factors sequence, period, treatment, and the random factor subject (within sequence). Within-treatment changes were analyzed using paired t-tests. All statistical tests of hypothesis were performed using a 0.05 level of significance. Since a stain-free baseline was employed and the only relevant parameter was the degree of increase in stain formation, the pairwise comparisons for this effect were performed using one-sided tests. Furthermore, kappa values were calculated using the repeat scores conducted by both examiners as a means of validating their scoring expertise. For the safety analyses, summary tabulations of oral soft tissue findings at each examination, and a listing of all adverse events reported were prepared. An adverse event was defined as treatment emergent if started after randomization. Results At baseline of the first 12-week period of the crossover, a total of 76 subjects were randomized equally into the two test groups. By the end of the second 12-week crossover period, a total of 69 subjects completed the entire study. All subjects not completing the study were lost to follow-up, except for one subject who was disqualified for non-compliance. As shown in Table I, the study population had a mean age of 44 years and was comprised of 55% females and 45% males. As mentioned previously, an approximately equal number of coffee drinkers, tea drinkers, and smokers (33%, 34%, 33%, respectively) participated in this study and represented those segments of the population most likely to develop extrinsic dental stain. Table I Baseline Subject Demographics Age Gender, N (%) Coffee Tea Smokers N (Mean ± SD) Male Female Drinkers Drinkers ± (45%) 42 (55%) 25 (33%) 26 (34%) 25 (33%) Table II displays the compliance data based on both the subject treatment diaries and the actual amounts of chewing gum and dentifrice used during the study. Based on subjects using eight gum pellets per day over the 12-week (85-day) study period, the calculated total amount of gum was 680 total pieces. The data show that subjects on average used 694 pieces, which was slightly more than the anticipated amount. Subjects were provided two extra pellets per day (ten pellets per pack) in case of loss, and they may have lost or failed to return some of these supplemental pellets between exams. The corresponding self-reported chewing gum diary data showed that the subjects completed approximately 99.9% of their required gum treatments. With regard to tooth brushing, subjects in each group were statistically comparable regarding the total weight of

4 40 The Journal of Clinical Dentistry Vol. XXV, No. 3 toothpaste used and the number of self-reported times they brushed during the 12-week study period. Both groups brushed on average once daily during the 85 days and used approximately 180 total grams of toothpaste (i.e., ~two grams/per brushing, which is typical for normal tooth brushing). Table III summarizes the average final LSI product scores (stain area multiplied by intensity) for the facial, lingual, and all surfaces of the anterior teeth after 12 weeks of chewing the test gum versus the no-gum control. These scores represent the amount of new stain that formed on the teeth of the subjects after a dental cleaning. For facial stain, average LSI stain scores of 0.65 and 0.41 were obtained for the no-gum control and chewing gum group, respectively. The test gum significantly (p < ) reduced stain forming on the facial surfaces by 37%. Final average LSI scores for lingual surfaces of 1.53 and 1.23 were obtained for the no-gum and gum groups, respectively, which represents a significant (p = 0018) 20% reduction in lingual stain formation by the test chewing gum. The total stain scores for all surfaces resulted in LSI values of 1.09 for the no-gum control and 0.82 for the test gum. Thus, the overall amount of stain forming on all surfaces of the anterior teeth was significantly (p = ) reduced by 25% when the subjects, in addition to tooth brushing, used the test chewing gum, compared to the same subjects not using chewing gum. Table IV presents the average final MLSI scores (stain area multiplied by intensity) for the facial, lingual, and all surfaces of the anterior teeth after 12 weeks of chewing the test gum versus the no-gum control. The overall findings were similar to the LSI data, except that a greater degree of separation was obtained between the two test groups with a higher level of statistical difference. For subjects using the test chewing gum, final MLSI scores of 0.37, 0.64, and 0.51 were obtained for the facial, lingual, and total tooth surfaces, respectively. The corresponding average scores for the no-gum control were all significantly greater at 0.60, 0.99, and 0.80, respectively. The test chewing Table II Subject Compliance for Chewing Gum and Dentifrice Usage gum was statistically significantly effective (p < ) in reducing new stain formation by 38% on facial surfaces, by 35% on lingual surfaces, and by 36% for all surfaces of the anterior teeth. In order to investigate the efficacy of the test chewing gum among the three types of stain formers, the LSI and MLSI stain data were analyzed separately for these subgroups. Since the subgroups had only about one-third of the total number of subjects, some loss in statistical power occurred as a result of the lower n value. Table V presents the final LSI scores for the two test groups according to coffee, tea, and cigarette users. Among the coffee drinkers, LSI scores of 0.98 and 0.70 were obtained for the no-gum control and test gum group, respectively. This represents a 29% reduction in stain formation, which was not statistically significantly different at p = For the cigarette smokers, a final LSI score of 1.33 versus 1.10 was obtained for the gum versus no-gum group. This represents a 17% stain reduction, which was not statistically different. For the tea drinkers, the chewing gum group resulted in a final stain score of 0.68 compared to 0.99 for the no-gum control. This 31% reduction in stain among tea drinkers was statistically significantly different at p = Table VI presents the final MLSI scores arranged according to the three population subgroups. The no-gum control group resulted in final MLSI scores 0.68, 0.98, and 0.74 for the coffee drinkers, smokers, and tea drinkers, respectively. The corresponding scores for the test gum group were all statistically significantly less at 0.41, 0.71, and 0.40, respectively. These data show that the test chewing gum was statistically significantly effective in reducing new stain formation by 40% in coffee drinkers (p = 0.004), by 28% for smokers (p = 0.019), and by 46% in tea drinkers (p < ). The separate stain area and intensity scores, which comprised the final composite stain scores (i.e., intensity x area), were also calculated and analyzed, but these separate data are not presented for brevity purposes. In general, the statistical findings for these Treatment Group Pieces of Gum Used* % Chewing Treatments* Wt. Dentifrice Used (gm)** Brushing Treatments** Orbit White Gum 694 ± % 179 ± ± 1 No Gum (control) ± ± 1 *Mean ± standard deviation, n=69. Theoretically, using eight pellets per day for 85 days = 680 total pieces. Chewing and brushing treatments were based on subject diaries. ** Mean ± standard deviation. There were no significant group differences in the amount of toothpaste used, or tooth brushing treatments over the 12-week trial period. Table III Final 12-Week Lobene Stain Index Scores (LSI) Anterior Teeth No Gum (Control) Orbit White Chewing Gum Difference Percent Reduction p-value Facial Stain 0.65 ± ± % < Lingual Stain 1.53 ± ± % Total Stain 1.09 ± ± % Mean LSI scores ± standard deviation, n=69; p-values are one-sided. Table IV Final 12-Week Modified Lobene Stain Index Scores (MLSI) Anterior Teeth No Gum (Control) Orbit White Chewing Gum Difference Percent Reduction p-value Facial Stain 0.60 ± ± % < Lingual Stain 0.99 ± ± % < Total Stain 0.80 ± ± % < Mean MLSI scores ± standard deviation, n=69; p-values are one-sided.

5 Vol. XXV, No. 3 The Journal of Clinical Dentistry 41 Table V Final 12-Week Lobene Stain Index Scores (LSI) for Population Subgroups Subgroup N No Gum (Control) Orbit White Chewing Gum Difference Percent Reduction p-value Coffee Users ± ± % Smokers ± ± % Tea Users ± ± % Mean LSI scores ± standard deviation; p-values are one-sided. Table VI Final 12-Week Modified Lobene Stain Index Scores (MLSI) for Population Subgroups Subgroup N No Gum (Control) Orbit White Chewing Gum Difference Percent Reduction p-value Coffee Users ± ± % Smokers ± ± % Tea Users ± ± % < Mean MLSI scores ± standard deviation; p-values are one-sided. two individual parameters paralleled the results for the product scores. Furthermore, the stain data from the interim six-week examination are also not presented for brevity purposes. In general, lesser amounts of stain had formed at this time point, and no statistically significant differences in total LSI (0.84 ± 0.78 vs ± 0.90) or MLSI scores (0.65 ± 0.70 vs ± 0.48) were observed between the no-gum control and the test gum group, respectively. During the course of the study, there were no observed or reported adverse events that were attributable to study test products or procedures, except for one case of a minor cheek bite that was possibly the result of gum chewing. Discussion In total, these clinical data demonstrated that the Orbit White chewing gum was a significant adjunct to tooth brushing in preventing stain from forming on the anterior teeth of subjects prone to accumulation of extrinsic stains, especially when chewed immediately after exposure to potential stain-inducing agents. One of the traditional uses of chewing gum has been after smoking, drinking coffee, or consuming odiferous foodstuffs as a means of freshening the breath and removing aftertastes, but this action may provide stain-reducing benefits as well. This test gum contained no claimed active agents, although a low percentage of baking soda was present. Therefore, the main mechanism of action was most likely salivary stimulation, which promoted the oral clearance of the stain-forming agents from the teeth and oral cavity. Also, the increased ph and buffering capacity of the stimulated saliva may have had some chemical impact on the chromogens. Analysis of the tooth surfaces showed that the test chewing gum was notably effective on the more visible facial surfaces of the front teeth (37% and 38% reductions in LSI and MLSI scores, respectively), despite the fact that greater amounts of stain formed on the lingual surfaces. This is important because subjects are more concerned about visual facial stains. Since chewing gum comes into minimal contact with the facial surfaces of the anterior teeth during mastication, this further suggests that the main mode of action for stain prevention was by salivary stimulation rather than by physical removal. The subjects selected for this study comprised approximately equal numbers of coffee drinkers, tea drinkers, and cigarette smokers who are known to form stain on their teeth over time despite regular tooth brushing. Subgroup analysis demonstrated that the test chewing gum significantly reduced new stain formation (MLSI scores) by 40% among coffee drinkers, by 28% among smokers, and by 46% among tea drinkers. The LSI scores showed a similar relationship, although only the stain reduction among tea drinkers (31%) was statistically significant. Since each subgroup consisted of only 22 to 24 people, it was very encouraging to find any statistical differences for the test groups with such small sample sizes. Overall, these data suggest that the chewing gum may be more effective among tea and coffee drinkers compared to cigarette smokers, indicative of a difference in the mechanism of stain deposition. In this study, comparable results were found by two separate dental examiners using different stain scoring indices. The test chewing gum significantly reduced new stain formation by 25% (p = ) based on the LSI and by 36% (p < ) using the MLSI. In general, the MLSI was better than the LSI in demonstrating the effectiveness of the test chewing gum. The MLSI was developed to improve upon the original LSI by including two additional components; that is, separate mesial and distal regions of the tooth, and by adding more scoring weight to the main areas of stain formation. Subject compliance and proper usage of the test products, which are critical in controlled clinical studies, were closely monitored in this study. Based on the treatment diaries and supported by the number of pieces of chewing gum used, compliance with instructions to use the assigned chewing gum four times each day during each 12-week trial period was excellent. Also, the amount of tooth brushing, which can influence stain removal, was comparable for each test group. Subjects were very receptive about the organoleptic properties of the test gum, and chewing the gum four times daily was well tolerated. Additionally, the subjects expressed no objections to using any of the test products, which might have raised concerns about compliance. Thus, comparisons between treatments for the clinical parameters were not influenced by compliance issues. No significant differences in stain formation between the test and control groups were observed at the interim six-week examination. This indicates that the level of new stain forming on the stain-free teeth had not sufficiently accumulated at this point in order to obtain a measurable difference in this population of stainforming subjects. Clinical studies designed to examine the inhibition of natural, as opposed to forced stain formation may require a minimum study period exceeding six weeks.

6 42 The Journal of Clinical Dentistry Vol. XXV, No. 3 Conclusion Compared to just tooth brushing alone (control), Orbit White chewing gum was found by two independent dental examiners using different stain scoring indices to statistically significantly reduce the formation of new dental stain on the anterior teeth of stain-susceptible subjects who chewed the gum over 12 weeks for 15 minutes four times/day soon after consuming coffee or tea or using tobacco. The gum was effective on both the facial and lingual tooth surfaces. Acknowledgments: The authors thank Kirstin Battershell, Colin Costin, James Bougoulas, and Paul Sadek for their significant contributions to this study. This study was supported by the Wm. Wrigley Jr. Co., Chicago, IL, USA. For correspondence with the authors of this paper, contact Dr. Jeffery L. Milleman milleman@salusresearch.us. References 1. Watts A, Addy M. Tooth discolouration and staining: a review of the literature. Br Dent J 2001;190, Dodds MW. The oral health benefits of chewing gum. J Ir Dent Assoc 2012;58: Soparkar P, Newman MB. Effects of a baking soda gum on extrinsic dental stain: results of a longitudinal 4-week assessment. Compend Contin Educ Dent 2001;22: Mankodi SM, Conforti N, Berkowitz H. Efficacy of baking soda-containing chewing gum on in removing natural tooth stain. Compend Contin Educ Dent 2001;22: Soparkar P, Newman MB. A clinical investigation to evaluate reduction in dental stain provided by the once daily use of a breath mint or chewing gum. Compend Contin Educ Dent 2001;22: Ozcan M, Kulak Y, Kazazoglu E. The efficacy of two prototype chewing gums for removal of extrinsic tooth stain. Int Dent J 2003;53: Yankell SL, Emling RC. Efficacy of chewing gum in preventing extrinsic tooth staining. J Clin Dent 1997;8: Biesbrock AR, Walters P, Bartizek RD. A chewing gum containing 7.5% sodium hexametaphosphate inhibits stain deposition relative to a placebo chewing gum. Compend Contin Educ Dent 2004;25: Bartizek RD, Walters P, Biesbrock AR. The prevention of induced stain using two levels of sodium hexametaphosphate in chewing gum. J Clin Dent 2003;14: Putt MS, Milleman JL, Kleber CJ, Nelson BJ. Inhibition of stain formation by baking soda/pyrophosphate chewing gum and dentifrice. J Dent Res 2002;81:A Lobene RR. Effect of dentifrices on tooth stains with controlled brushing. J Am Dent Assoc 1968;77: Lobene RR. Clinical studies of the cleaning functions of dentifrices. J Am Dent Assoc 1982;105: Macpherson LMD, Stephen KW, Schafer F, Joiner A. Extrinsic tooth stain after six weeks of normal dentifrice use. J Dent Res 1996;75(Spec Iss): Macpherson LMD, Stephen KW, Joiner A, Schafer F, Huntington E. Comparison of a conventional and modified tooth stain index. J Clin Periodontol 2000;27:854-9.

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