Effect of addition of citric acid and casein phosphopeptide-amorphous calcium phosphate to a sugar-free chewing gum on enamel remineralization in situ

Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) has been shown to remineralize enamel subsurface lesions in situ. The aim of this study was to investigate the effects of CPP-ACP in a fruit-flavoured sugar-free chewing gum containing citric acid on enamel remineralization, and acid resistance of the remineralized enamel, using an in situ remineralization model. The study utilized a double-blind, randomized, crossover design with three treatments: (i) sugar-free gum (2 pellets) containing 20 mg citric acid and 18.8 mg CPP-ACP, (ii) sugar-free gum containing 20 mg citric acid alone, (iii) sugar-free gum not containing CPP-ACP or citric acid. Ten subjects were instructed to wear removable palatal appliances, with 4 half-slab insets of human enamel containing demineralized subsurface lesions and to chew gum (2 pellets) for 20 min 4 times per day for 14 days. At the completion of each treatment the enamel half-slabs were removed and half of the remineralized lesion treated with demineralization buffer for 16 h in vitro. The enamel slabs (remineralized, acid-challenged and control) were then embedded, sectioned and subjected to microradiography to determine the level of remineralization. Chewing with gum containing citric acid and CPP-ACP resulted in significantly higher remineralization (13.0 +/- 2.2%) than chewing with either gum containing no CPP-ACP or citric acid (9.4 +/- 1.2%) or gum containing citric acid alone (2.6 +/- 1.3%). The acid challenge of the remineralized lesions showed that the level of mineral after acid challenge was significantly greater for the lesions exposed to the gum containing CPP-ACP.     

Acid resistance of enamel subsurface lesions remineralized by a sugar-free chewing gum containing casein phosphopeptide-amorphous calcium phosphate

The aim of this clinical study was to investigate the acid resistance of enamel lesions remineralized in situ by a sugar-free chewing gum containing casein phosphopeptide-amorphous calcium phosphate nanocomplexes (CPP-ACP: Recaldent). The study utilized a double-blind, randomized, crossover design with two treatments: (i) sugar-free gum containing 18.8 mg of CPP-ACP, and (ii) sugar-free gum not containing CPP-ACP as control. Subjects wore removable palatal appliances with insets of human enamel containing demineralized subsurface lesions and chewed the gum for 20 min 4 times per day for 14 days. After each treatment the enamel slabs were removed and half of each lesion challenged with acid in vitro for 8 or 16 h. The level of remineralization was determined using microradiography. The gum containing CPP-ACP produced approximately twice the level of remineralization as the control sugar-free gum. The 8- and 16-hour acid challenge of the lesions remineralized with the control gum resulted in 65.4 and 88.0% reductions, respectively, of deposited mineral, while for the CPP-ACP-remineralized lesions the corresponding reductions were 30.5 and 41.8%. The acid challenge after in situ remineralization for both control and CPP-ACP-treated lesions resulted in demineralization underneath the remineralized zone, indicating that the remineralized mineral was more resistant to subsequent acid challenge. The results show that sugar-free gum containing CPP-ACP is superior to an equivalent gum not containing CPP-ACP in remineralization of enamel subsurface lesions in situ with mineral that is more resistant to subsequent acid challenge.     

Remineralization of enamel subsurface lesions in situ by sugar-free lozenges containing casein phosphopeptide-amorphous calcium phosphate

BACKGROUND: The anticariogenic potential of casein phosphopeptide-amorphous calcium phosphate nanocomplexes (CPP-ACP) has been demonstrated using laboratory, animal and human in situ caries models. The aim of this study was to determine the effect of CPP-ACP incorporation into a sugar-free lozenge (pressed mint tablet) on enamel remineralization in a human in situ model. METHODS: The study utilized a double-blind, randomized, cross-over design with four treatments: (i) a lozenge containing 56.4mg (3 per cent w/w) CPP-ACP; (ii) a lozenge containing 18.8mg (1 per cent w/w) CPP-ACP; (iii) a lozenge not containing CPP-ACP; and (iv) a no lozenge nil-treatment control. Ten subjects wore removable palatal appliances with four, human-enamel, half-slab insets containing subsurface lesions. Lozenges were consumed, without chewing, four times per day for 14 days duration. After each treatment period the enamel slabs were removed, paired with their respective demineralized control, embedded, sectioned and subjected to microradiography and computer-assisted densitometric image analysis to determine the level of remineralization. RESULTS: The incorporation of CPP-ACP into the lozenge significantly increased enamel subsurface lesion remineralization with 18.8 and 56.4mg of CPP-ACP increasing remineralization by 78 and 176 per cent respectively, relative to the control sugarfree lozenge. CONCLUSION: This study demonstrates that lozenges are a suitable vehicle for the delivery of CPP-ACP to promote enamel remineralization.     

Remineralization of enamel subsurface lesions in situ by the use of three commercially available sugar-free gums

Background.  Commercially available sugar-free chewing gums have been claimed to provide oral health benefits.
Aim.  The aim of this randomized, double-blind crossover in situ study was to compare the efficacy of three commercially available sugar-free chewing gums: Trident White, Orbit, and Orbit Professional, in remineralizing enamel subsurface lesions in situ .
Design.  Specimens containing enamel subsurface lesions were sectioned into test and control half-slabs with the test half-slabs inserted into removable palatal appliances. For each test chewing period, subjects were randomly allocated one of three test gums. Subjects ( n  = 10) chewed the randomly allocated gum for a 20-min period four times per day for 14 days. Each subject chewed all three test gums, with a 7-day washout period between crossovers. After each 14-day cycle, test and control half-slabs were paired, embedded in resin, sectioned, and subjected to microradiography to determine remineralization.
Results.  The gum TW produced significantly greater remineralization (18.4 ± 0.9%) than Orbit (8.9 ± 0.5%) and Orbit Professional (10.5 ± 0.9%).
Conclusion.  The superior remineralization activity of the TW gum in situ was attributed to the presence of casein phosphopeptide–amorphous calcium phosphate nanocomplexes.     

Retention in plaque and remineralization of enamel lesions by various forms of calcium in a mouthrinse or sugar-free chewing gum

Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) nanocomplexes incorporated into sugar-free chewing gum have been shown to remineralize enamel subsurface lesions in situ. The aim of this study was to compare the ability of CPP-ACP, with that of other forms of calcium, to be retained in supragingival plaque and remineralize enamel subsurface lesions in situ when delivered in a mouthrinse or sugar-free gum in randomized, double-blind trials. In the mouthrinse study, only the CPP-ACP-containing mouthrinse significantly increased plaque calcium and inorganic phosphate levels, and the CPP were immunolocalized to the surfaces of bacterial cells as well as the intercellular matrix. In the chewing gum studies, the gum containing the CPP-ACP, although not containing the most calcium per piece of gum, produced the highest level of enamel remineralization independent of gum-chewing frequency and duration. The CPP could be detected in plaque extracts 3 hrs after subjects chewed the CPP-ACP-containing gum. The results showed that CPP-ACP were superior to other forms of calcium in remineralizing enamel subsurface lesions.     

Effect of casein phosphopeptide - amorphous calcium phosphate containing chewing gum on salivary concentration of calcium and phosphorus: An in-vivo study

Aim: Caries clinical trials of sugar-free chewing gum have shown that the gum is noncariogenic and in fact has anticariogenic effect through the stimulation of saliva. Sugar-free gums, therefore, may be an excellent delivery vehicle for safe and effective additive, capable of promoting enamel remineralization. Casein phosphopeptide - amorphous calcium phosphate (CPP-ACP) nanocomplexes incorporated into sugar-free chewing gum have shown to remineralize enamel subsurface lesions in situ. So this study was conducted to evaluate the effect of CPP-ACP containing sugar-free chewing gum on salivary concentration of calcium and phosphorous. Materials and Methods : Unstimulated saliva from each 24 selected subjects was collected. Then each subject was given two pellets of chewing gum containing CPP-ACP and asked to chew for a period of 20 min, after which saliva samples were collected from each individual. Once all the samples were collected they were assessed for calcium and phosphorous concentration using affiliated reagent kits and photometer. Statistical Analysis Used: Data obtained were analyzed using student's paired t test. Results: Significant difference was found in the calcium and phosphorus concentration of saliva before and after chewing CPP-ACP containing chewing gum. Conclusions: Chewing of CPP-ACP containing chewing gum showed a significant increase in the salivary concentration of calcium for a prolonged period of time hence it may help in the remineralization of tooth surfaces.     

Remineralisation by chewing sugar-free gums in a randomised, controlled in situ trial including dietary intake and gauze to promote plaque formation

Remineralisation has been shown to be an effective mechanism of preventing the progression of enamel caries. The aim of this double-blind, randomised, cross-over in situ study was to compare enamel remineralisation by chewing sugar-free gum with or without casein phosphopeptide amorphous calcium phosphate (CPP-ACP) where the enamel lesions were exposed to dietary intake and some were covered with gauze to promote plaque formation. Participants wore removable palatal appliances containing 3 recessed enamel half-slabs with subsurface lesions covered with gauze and 3 without gauze. Mineral content was measured by transverse microradiography, and plaque composition was analysed by real-time polymerase chain reaction. For both the gauze-free and gauze-covered lesions, the greatest amount of remineralisation was produced by the CPP-ACP sugar-free gum, followed by the gum without CPP-ACP and then the no-gum control. Recessing the enamel in the appliance allowed plaque accumulation without the need for gauze. There was a trend of less remineralisation and greater variation in mineral content for the gauze-covered lesions. The cell numbers of total bacteria and streptococci were slightly higher in the plaque from the gauze-covered enamel for 2 of the 3 treatment legs; however, there was no significant difference in Streptococcus mutans cell numbers. In conclusion, chewing sugar-free gum containing CPP-ACP promoted greater levels of remineralisation than a sugar-free gum without CPP-ACP or a no-gum control using an in situ remineralisation model including dietary intake irrespective of whether gauze was used to promote plaque formation or not.     

Consumption of milk with added casein phosphopeptide-amorphous calcium phosphate remineralizes enamel subsurface lesions in situ

Background:  Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) is an anticariogenic agent that is suitable to be added to foods. The aim of this double-blind, three-way crossover randomized study was to investigate the capacity of CPP-ACP, when added to bovine milk, to remineralize enamel subsurface lesions in situ .
Methods:  Ten subjects drank 100 mL of bovine milk containing no added CPP-ACP (control milk), 0.2% (w/v) CPP-ACP or 0.3% (w/v) CPP-ACP, for 30 seconds once daily for 15 days, whilst wearing removable appliances with attached slabs of enamel containing subsurface enamel lesions. After each treatment and a one-week washout period, subjects crossed over to another treatment and this was repeated until they had consumed each of the three milk products. At the completion of each treatment the enamel slabs were removed and remineralization was determined using microradiography.
Results:  The results demonstrated that all three milk samples remineralized enamel subsurface lesions in situ . However, the two milk samples containing added CPP-ACP each produced significantly greater remineralization than the control milk.
Conclusions:  The remineralizing effect of CPP-ACP in milk was dose-dependent with milk containing 0.2% CPP-ACP and 0.3% CPP-ACP producing an increase in mineral content of 81% and 164%, respectively, relative to the control milk.     

Comparison of the remineralization potential of CPP-ACP and CPP-ACP with 900 ppm fluoride on eroded human enamel: An in situ study

Objective

The aim of this in situ study was to compare the remineralization potential of pastes containing CPP-ACP and CPP-ACP with 900 ppm fluoride on human enamel softened by a cola drink.

Design

Forty-five enamel specimens obtained from human third molar teeth were eroded in a cola drink for 8 min and then attached to intra-oral devices worn by five volunteers. The specimens were subjected to three different in situ remineralization protocols using: (1) CPP-ACP (Group I), (2) CPP-ACP with 900 ppm fluoride (Group II), and (3) saliva (Group III, control). Vickers microhardness measurements were obtained at baseline followed by demineralization and remineralization stages.

Results

The CPP-ACP, CPP-ACP with 900 ppm fluoride and saliva controls resulted in 46.24%, 64.25% and 2.98% increase in post-erosion microhardness values, respectively. One-way ANOVA revealed statistically significant differences in the mean microhardness values between pastes containing CPP-ACP and CPP-ACP with 900 ppm fluoride.

Conclusions

Both CPP-ACP and CPP-ACP with 900 ppm fluoride substantially remineralized the softened enamel, with the CPP-ACP and fluoride combination showing higher remineralization potential than CPP-ACP. This study confirmed the synergistic effect of fluoride with CPP-ACP on remineralization of eroded enamel.     

The effect of chewing gum use on in situ enamel lesion remineralization.

Two independent cross-over studies investigated the possibility of enhanced early enamel lesion remineralization with the use of chewing gum. The first study involved a sorbitol-containing chewing gum, and the second, which had an identical protocol, tested a sucrose-containing chewing gum. In each study, 12 volunteers wore in situ appliances on which were mounted enamel sections containing artificial caries lesions. Subjects brushed twice daily for two min with a 1100-ppm-F (NaF) dentifrice (control and test) and in the test phase chewed five sticks of gum per day for 20 min after meals and snacks. Microradiographs of the enamel lesions were made at baseline and at the end of the seven-week experimental period. In the sugar-free gum study, the weighted mean total mineral loss (delta z) difference [(wk7-wk0) x (-1)] was 788 vol.% min. x micron for the gum, corresponding to remineralization of 18.2%, vs. the control value of 526 vol.% min. x micron, 12.1% remineralization (p = 0.07). There were no significant differences for the surface-zone (p = 0.20) and lesion-body (p = 0.28) values. In the sucrose-containing gum study, the delta z difference was 743 vol.% min. x micron for the gum, corresponding to a remineralization of 18.3%, vs. the control value of 438 vol.% min. x micron, 10.8% remineralization (p = 0.08). The surface-zone values were not significantly different (p = 0.55). For the lesion body, however, the sucrose-containing gum value of 6.11 vol.% min. was significantly different (p = 0.01) from that of the control (2.81 vol.% min.).     

酪蛋白磷酸肽-无定形磷酸钙对正畸术后釉质再矿化的效果评价

目的: 比较含氟漱口水、护牙素即酪蛋白磷酸肽-无定形磷酸钙（casein phosphopeptide calcium phosphate complex,CPP-ACP）对正畸治疗后发生釉质脱矿的再矿化效果。方法: 应用Image J图像分析技术观察正畸治疗后釉质的再矿化。将固定矫治器正畸治疗后发生牙釉质脱矿的21例患者（女13例,男8例,84颗患牙）分为3组,每组28颗患牙。对照组仅用含氟牙膏每天刷牙2次,每次3 min。氟化物组用含氟牙膏每天刷牙2次,每次3 min,同时使用20 mL 0.01%氟化物冲洗牙2次。CPP-ACP组用含氟牙膏每天刷牙2次,每次3 min。同时按要求使用CPP-ACP 2次,3组均持续使用6个月。采用SPSS17.0软件包对数据进行统计学分析。结果: 正畸治疗后6个月,3组牙釉质脱矿白斑区域面积均有不同程度减少,3组治疗前、后均有显著差异（P<0.05）。CPP-ACP组效果尤为明显（51.68%）,显著高于氟化物组（44.42%）和对照组（42.71%）。结论: 正畸治疗后6个月内,正确刷牙、氟化物漱口、配合护牙素的使用,对正畸治疗中脱矿牙的再矿化均有一定效果, 而且CPP-ACP可以更有效地减小牙釉质脱矿白斑区域面积。     

Remineralization of enamel subsurface lesions by chewing gum with added calcium

Objectives

Chewing sugar-free gum has been shown to promote enamel remineralization. Manufacturers are now adding calcium to the gum in an approach to further promote enamel remineralization. The aim of this study was to compare the remineralization efficacy of four sugar-free chewing gums, two containing added calcium, utilizing a double-blind, randomized, crossover in situ model.

Methods

The sugar-free gums were: Trident Xtra Care, Orbit Professional, Orbit and Extra. Ten subjects wore removable palatal appliances with four human-enamel half-slab insets containing subsurface demineralized lesions. For four times a day for 14 consecutive days subjects chewed one of the chewing gums for 20 min. After each treatment the enamel slabs were removed, paired with their respective demineralized control slabs, embedded, sectioned and mineral level determined by microradiography. After 1-week rest the subjects chewed another of the four gums and this was repeated until each subject had used the four gum products.

Results

Chewing with Trident Xtra Care resulted in significantly higher remineralization (20.67 ± 1.05%) than chewing with Orbit Professional (12.43 ± 0.64%), Orbit (9.27 ± 0.59%) or Extra (9.32 ± 0.35%). The form of added calcium in Trident Xtra Care was CPP–ACP and that in Orbit Professional calcium carbonate with added citric acid/citrate for increased calcium solubility.

Conclusions

Although saliva analysis confirmed release of the citrate and calcium from the Orbit Professional gum the released calcium did not result in increased enamel remineralization over the normal sugar-free gums. These results highlight the importance of calcium ion bioavailability in the remineralization of enamel subsurface lesions in situ.     

In situ evaluation of different remineralization periods to decrease brushing abrasion of demineralized enamel

The aim of the present in situ study was to evaluate the effect of different periods of intraoral remineralization to decrease the susceptibility of previously demineralized enamel against toothbrushing abrasion. Six human enamel specimens (A-F) were recessed in the buccal aspects of each of eight intraoral appliances which were worn for 21 days by 8 panelists. Demineralization of the samples was performed twice a day extraorally in the acidic beverage Sprite Light for 90 s. Subsequently, the enamel specimens were brushed at different times. Specimen A was brushed immediately after the demineralization. The remaining samples B-E were brushed after the intraoral appliances had been worn for various periods of remineralization: specimen B, 10 min; C, 20 min; D, 30 min and E, 60 min, respectively. Specimen F was only demineralized and remineralized, but not brushed. After 21 days, enamel wear was measured with a laser profilometer. The following values (mean +/- standard deviation) were obtained: specimen A, 6.78+/-2.71 microm; B, 5.47+/-3.39 microm; C, 6.06+/-3.18 microm; D, 5.43+/-2.58 microm; E 4.78+/-2.57 microm, and F 0.66+/-1.11 micro;m. Analysis of variance revealed a significant influence of remineralization period on abrasive wear. However, even after a remineralization period of 60 min the wear was significantly increased as compared to the demineralized, but not brushed control. It is concluded that (1) abrasion resistance of softened enamel increases with remineralization period and (2) at least 60 min should elapse before toothbrushing after an erosive attack.     

Fluoride and casein phosphopeptide-amorphous calcium phosphate

Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) slows the progression of caries and remineralizes enamel subsurface lesions. The aim of this study was to determine the ability of CPP-ACP to increase the incorporation of fluoride into plaque and to promote enamel remineralization in situ. Randomized, double-blind, cross-over studies involved mouthrinses and dentifrices containing CPP-ACP and fluoride. The mouthrinses were used for 60 sec, three times/day for 5 days, and supragingival plaque was collected and analyzed for F. The dentifrices were rinsed as a water slurry for 60 sec four times/day for 14 days in an in situ model. The addition of 2% CPP-ACP to the 450-ppm-F mouthrinse significantly increased the incorporation of fluoride into plaque. The dentifrice containing 2% CPP-ACP produced a level of remineralization similar to that achieved with a dentifrice containing 2800 ppm F. The dentifrice containing 2% CPP-ACP plus 1100 ppm F was superior to all other formulations.     

Use of laser fluorescence and scanning electron microscope to evaluate remineralization of incipient enamel lesions remineralized by topical application of casein phospho peptide amorphous calcium phosphate (CPP-aCP) containing cream

The aim of this in vitro study was to evaluate the remineralization of incipient enamel lesions by the topical application of Casein PhosphoPeptide-Amorphous Calcium Phosphate (CPP-ACP) using laser fluorescence and scanning electron microscope. Sixty caries free extracted teeth were used in the study. Forty teeth were used as test samples, ten as positive and ten as negative controls. The samples were demineralized and then remineralized by the topical application of CPP-ACP for a period of 14 days. The remineralization was evaluated with the use of laser fluorescence and scanning electron microscope (SEM). The results of this study showed that the laser fluorescent readings of test samples after remineralization were highly significant (p < 0.001). A significant number of test samples observed under SEM showed high scores of remineralization.     

Remineralization of artificial caries-like lesions in human enamel in situ by chewing sorbitol gum

The objective of the study was to determine quantitatively the effect on the potential for in situ remineralization of artificial caries-like lesions in human enamel when sugar-free gum containing mainly sorbitol as sweetener was chewed after meals and snacks. Artificial white-spot lesions were created in extracted human premolars and divided into three parts. One part was used as reference and the other two worn consecutively for two 21-day periods by 10 volunteers in a cast silver band cemented on lower molar teeth and covered with gauze to promote plaque formation. During the experimental periods, the subjects used fluoridated toothpaste twice daily, and consumed three meals (breakfast, lunch, and dinner) and two snacks (selected from chocolate bar, raisins, chocolate wafer, and iced cupcake). Sorbitol gum was chewed for 20 min immediately after each meal or snack during one of the experimental periods. The three parts of the enamel lesions were then sectioned (congruent to 80 microns) and examined together by means of quantitative microradiography and by polarized light microscopy. All estimates of mineral content indicated that significant remineralization occurred and was approximately doubled with gum-chewing. It is suggested that sorbitol gum stimulates salivation, which is responsible for the significantly enhanced remineralization, thus contributing to a therapeutic, caries-preventive effect. Because the gum was chewed immediately after meals and snacks, inhibition of demineralization may also have occurred.     

CPP-ACP与不同浓度氟促进釉质再矿化的研究

目的：探讨酪蛋白磷酸多肽-无定形磷酸钙(casein phosphopeptide-amorphous calcium phosphate,CPP-ACP) 与不同浓度氟离子联合应用对脱矿釉质再矿化的作用。方法：取正畸拔除的健康前磨牙30颗,乳酸凝胶法制备人工早期釉质脱矿后, 随机分为对照组(5% CPP-ACP组)、实验组1(5% CPP-ACP+500 mg/L F-组)和实验组2(5% CPP-ACP+900 mg/L F-组),采用MH-5型显微硬度仪测量处理前、后釉质标本的显微硬度,采用SPSS 18.0软件包对数据进行统计学分析。结果：显微硬度测量显示,实验组2牙釉质的表面显微硬度变化显著高于实验组1(P<0.05)及对照组(P<0.01)。结论：CPP-ACP能够促进脱矿釉质再矿化,氟对其有加强协同作用。在一定范围内,氟浓度越高,协同作用越好。     

Enamel Demineralization Prevention during Fixed Orthodontic Treatment and Remineralization Strategies

Preventing enamel demineralization and remineralization of orthodontic patients is important and it di-ffers from other dental patients. Oral hygiene education and oral examination is essential to prevent enamel demi-neralization, and dietary education or control of sugar intake should not be ignored during fixed orthodontic treat-ment. Laser irradiation is a noteworthy method to prevent enamel mineralization. Products containing fluoride andfluoride released not only can be used to prevent demineralization but also have the ability of remineralization during orthodontic treatment. Oral hygiene products containing casein-phosphopeptide amorphous calcium phosphate(CPP-ACP) have been demonstrated to have the ability of remineralization such as sugar-free chewing gum added CPP-ACP, lozenges containing CPP-ACP and milk protein casein stabilized by phosphopeptides.     

Evaluation of the anticaries benefit of fluoride toothpastes using an enamel insert model

The remineralization potential of fluoride toothpastes was studied using an in situ enamel insert model. Matched blocks of artificially demineralized human enamel were attached to partial dentures of 16 adult volunteers who brushed their teeth with either a toothpaste containing 1,500 ppm F or one containing 2,500 ppm F for a period of 6 weeks in a balanced, randomized crossover experiment. Computerized image analysis of microradiographs was used to measure the mineral density distribution in the enamel before and after in situ treatment. Both toothpastes demonstrated remineralization of artificial carious lesions. Significantly more remineralization was observed in enamel samples treated with the toothpaste containing 2,500 ppm F compared to that containing 1500 ppm F. This result is consistent with the outcome of a recent caries clinical trial testing the same toothpastes and finding enhanced anticaries efficacy from the higher fluoride level.     

Delivery of active agents from chewing gum for improved remineralization

Most surrogate measures of caries were developed to test products containing fluoride, typically at relatively high and closely controlled oral concentrations. However, since the primary mechanism for the remineralization of early enamel caries lesions by chewing gum is through stimulation of saliva, delivering Ca and Pi to the demineralized enamel lesion, established methods may lack the sensitivity to detect the additional benefit of an active agent without the strong remineralizing potential of fluoride. Issues related to the release of active agents from the gum matrix, dilution in the saliva, and limited oral retention time, along with taste, safety, regulatory, and cost concerns, impose further limitations. This paper reviews the efficacy of some active agents used in chewing gum for improved remineralization and includes results from in situ testing of calcium-containing gums, including calcium lactate, tetracalcium phosphate/dicalcium phosphate anhydrous, calcium citrate/encapsulated phosphate, and a calcium lactate/sodium phosphate blend. Despite promising in vitro data from these agents, they did not provide consistently superior results from in situ testing. There is a need to develop better predictive in vitro models for chewing gum, as well as improved sensitivity of in situ models to discriminate relatively small amounts of remineralization against a background of high biological variability.