Addition of Povidone-Iodine to Fluoride Varnish for Dental Caries: A Randomized Clinical Trial.

INTRODUCTION: Dental caries is the most common chronic childhood disease. Products of metabolism by bacteria populating the tooth surface induce development and progression of cavities. OBJECTIVES: We sought to determine whether a polyvinylpyrrolidone-iodine (PVP-I; povidone-iodine) and NaF topical varnish was superior to one containing only NaF in prevention of new dental caries lesions in a single-center randomized active-controlled trial based on a double-blind, parallel-group design. METHODS: The site was Pohnpei State, Federated States of Micronesia. The study population was healthy children 49 to 84 mo old who were enrolled in early childhood education: 284 were randomized (1:1 allocation), and 273 were included in year 1 analysis and 262 in year 2. The test varnish contained 10% PVP-I and 5.0% NaF. The comparator contained only 5.0% NaF but was otherwise identical. Varnishes were applied every 3 mo during 2 y. The primary outcome was the surface-level primary molar caries lesion increment (d2-4mfs) at 2 y. Caries lesion increments from baseline to year 1 and year 2 were compared between conditions with log-linear regression, adjusting for age and sex and whether the tooth was sound at baseline (free of caries lesions). RESULTS: At year 1, the caries lesion increment for primary molars sound at baseline was 0.9 surfaces (SD = 1.5) for the test varnish versus 1.8 (SD = 2.2) for the comparator varnish with fluoride alone (adjusted rate ratio, 0.50; 95% CI, 0.31 to 0.81; P = .005). At year 2, the caries lesion increment for primary molars sound at baseline was 2.3 surfaces (SD = 2.8) for the test varnish as compared with 3.3 (SD = 2.7) for the comparator (adjusted rate ratio, 0.74; 95% CI, 0.52 to 1.03; P = .073). Teeth that were already cavitated at baseline did not show a preventive effect. There were no harms. CONCLUSIONS: A dental varnish containing PVP-I and NaF is effective in the primary prevention of cavities in the primary dentition (NCT03082196). KNOWLEDGE TRANSFER STATEMENT: This study demonstrates that periodic application of a varnish containing NaF and PVP-I is effective in prevention of caries lesions and useful in assessing the potential of combined treatment.

Streptococcus mutans out-competes Streptococcus gordonii in vivo.

Streptococcus gordonii and Streptococcus mutans avidly colonize teeth. S. gordonii glucosyltransferase (GtfG) and amylase-binding proteins (AbpA/AbpB), and S. mutans glucosyltransferase (GtfB), affect their respective oral colonization abilities. We investigated their interrelationships and caries association in a rat model of human caries, examining the sequence of colonization and non- vs. high-sucrose diets, the latter being associated with aggressive decay in humans and rats. Virulence-characterized wild-types of both species and well-defined mutants of S. gordonii with interrupted abpA and gtfG genes were studied. While both S. gordonii and S. mutans were abundant colonizers of rat's teeth in the presence of either diet, if inoculated singly, S. mutans always out-competed S. gordonii on the teeth, independent of diet, strain of S. mutans, simultaneous or sequential inoculation, or presence/absence of mutations of S. gordonii's abpA and gtfG genes known to negatively or positively affect its colonization and to interact in vitro with S. mutans GtfB. S. mutans out-competed S. gordonii in in vivo plaque biofilm. Caries induction reflected S. mutans or S. gordonii colonization abundance: the former highly cariogenic, the latter not. S. gordonii does not appear to be a good candidate for replacement therapy. These results are consistent with human data.

Caries inhibition by and safety of Lactobacillus paracasei DSMZ16671.

Lactobacillus paracasei DSMZ16671, even if heat-killed, sensitively co-aggregates mutans streptococci specifically. Mutans streptococci are strongly implicated in caries induction in humans and rodents. We hypothesized: (1) that S. mutans recoveries from rats' teeth in vivo will decrease, with an associated decrease in caries, if these lactobacilli are fed to rats in an established caries model; and (2) that toxicological assays of these lactobacilli will show them to be benign. Four groups of specific-pathogen-free rats were formed: S. mutans 10449S-inoculated/16671-supplemented diet; un-inoculated/16671-supplemented diet; S. mutans 10449S-inoculated/placebo diet; and un-inoculated/placebo diet. Standard tests of toxicity and mutagenicity of heat-killed DSMZ16671 were performed. S. mutans recoveries were significantly reduced both in mid-experiment and at termination, as were caries lesion scores for the rats inoculated by S. mutans and fed the DSMZ16671 supplement, by comparison with controls. Neither toxicity nor mutagenicity of DSMZ16671 was detected. Use of heat-killed DSMZ16671 is efficacious in rats and appears safe.

Specific Lactobacillus/Mutans Streptococcus co-aggregation.

Selective interaction of mutans streptococci with benign bacteria could present an opportunity for their removal from the mouth without disruption of other oral flora. This study was conducted to find probiotic lactobacilli that could specifically co-aggregate in vitro with mutans streptococci, but not with other plaque commensals. A search of 624 lactobacilli among a large culture library revealed 6 strains, all classifiable as L. paracasei or L. rhamnosus, which met this criterion. Such novel, specific co-aggregation, however, was not a general characteristic of these species or the genus Lactobacillus. The co-aggregation by these specific lactobacilli was characterized as heat treatment (autoclaving)- and protease-resistant, lectin-independent, not inactivated by sugar substitutes, operational over a wide pH range, unaffected by whole saliva, but calcium-dependent. It is thus seen to present a potential strategy for in vivo alteration of plaque biofilm and caries.

Streptococcus gordonii's sequenced strain CH1 glucosyltransferase determines persistent but not initial colonization of teeth of rats.

OBJECTIVE: Extracellular glucan synthesis from sucrose by Streptococcus gordonii, a major dental plaque biofilm bacterium, is assumed important for colonization of teeth; but this hypothesis is un-tested in vivo. METHODS: To do so, we studied an isogenic glucosyltransferase (Gtf)-negative mutant (strain AMS12, gtfG(-)) of S. gordonii sequenced wild type (WT, strain Challis CH1, gtfG(+)), comparing their in vitro abilities to grow in the presence of glucose and sucrose and, in vivo, to colonize and persist on teeth and induce caries in rats. Weanling rats of two breeding colonies, TAN:SPFOM(OM)BR and TAN:SPFOM(OMASF)BR, eating high sucrose diet, were inoculated with either the WT (gtfG(+)), its isogenic gtfG(-) mutant, or reference strains of Streptococcus mutans. Control animals were not inoculated. RESULTS: In vitro, the gtfG(-) strain grew at least as rapidly in the presence of sucrose as its WT gtfG(+) progenitor, but formed soft colonies on sucrose agar, consistent with its lack of insoluble glucan synthesis. It also had a higher growth yield due apparently to its inability to channel carbon flow into extracellular glucan. In vivo, the gtfG(-) mutant initially colonized as did the WT but, unlike the WT, failed to persist on the teeth as shown over time. By comparison to three S. mutans strains, S. gordonii WT, despite its comparable ecological success on the teeth, was associated with only modest caries induction. Failure of the gtfG(-) mutant to persistently colonize was associated with slight diminution of caries scores by comparison with its gtfG(+) WT. CONCLUSIONS: Initial S. gordonii colonization does not depend on Gtf-G synthesis; rather, Gtf-G production determines S. gordonii's ability to persist on the teeth of sucrose-fed rats. S. gordonii appears weakly cariogenic by comparison with S. mutans reference strains.

Streptococcus mutans: fructose transport, xylitol resistance, and virulence.

Streptococcus mutans, the primary etiological agent of human dental caries, possesses at least two fructose phosphotransferase systems (PTSs), encoded by fruI and fruCD. fruI is also responsible for xylitol transport. We hypothesized that fructose and xylitol transport systems do not affect virulence. Thus, colonization and cariogenicity of fruI(-) and fruCD(-) single and double mutants, their WT (UA159), and xylitol resistance (X(r)) of S. mutans were studied in rats fed a high-sucrose diet. A sucrose phosphorylase (gtfA(-)) mutant and a reference strain (NCTC-10449S) were additional controls. Recoveries of fruI mutant from the teeth were decreased, unlike those for the other strains. The fruCD mutation was associated with a slight loss of cariogenicity on enamel, whereas mutation of fruI was associated with a loss of cariogenicity in dentin. These results also suggest why xylitol inhibition of caries is paradoxically associated with spontaneous emergence of so-called X(r) S. mutans in habitual human xylitol users.

Amylase-binding proteins A (AbpA) and B (AbpB) differentially affect colonization of rats' teeth by Streptococcus gordonii.

Streptococcus gordonii produces two alpha-amylase-binding proteins, AbpA and AbpB, that have been extensively studied in vitro. Little is known, however, about their significance in oral colonization and cariogenicity (virulence). To clarify these issues, weanling specific pathogen-free Osborne-Mendel rats, TAN : SPFOM(OM)BR, were inoculated either with wild-type strains FAS4-S or Challis-S or with strains having isogenic mutations of abpA, abpB, or both, to compare their colonization abilities and persistence on the teeth. Experiments were done with rats fed a sucrose-rich diet containing low amounts of starch or containing only starch. The mutants and wild-types were quantified in vivo and carious lesions were scored. In 11 experiments, S. gordonii was a prolific colonizer of the teeth when rats were fed the sucrose (with low starch)-supplemented diet, often dominating the flora. Sucrose-fed rats had several-fold higher recoveries of inoculants than those eating the sucrose-free, starch-supplemented diet, regardless of inoculant type. The strain defective in AbpB could not colonize teeth of starch-only-eating rats, but could colonize rats if sucrose was added to the diet. Strains defective in AbpA surprisingly colonized better than their wild-types. A double mutant deficient in both AbpA and AbpB (abpA/abpB) colonized like its wild-type. Wild-types FAS4-S and Challis-S had no more than marginal cariogenicity. Notably, in the absence of AbpA, cariogenicity was slightly augmented. Both the rescue of colonization by the AbpB- mutant and the augmentation of colonization by AbpA- mutant in the presence of dietary sucrose suggested additional amylase-binding protein interactions relevant to colonization. Glucosyltransferase activity was greater in mutants defective in abpA and modestly increased in the abpB mutant. It was concluded that AbpB is required for colonization of teeth of starch-eating rats and its deletion is partially masked if rats eat a sucrose-starch diet. AbpA appears to inhibit colonization of the plaque biofilm in vivo. This unexpected effect in vivo may be associated with interaction of AbpA with glucosyltransferase or with other colonization factors of these cells. These data illustrate that the complex nature of the oral environment may not be adequately modelled by in vitro systems.

Novel sucrose-dependent adhesion co-factors in Streptococcus mutans.

Streptococcus mutans glucosyltransferases form extracellular glucans from sucrose to promote adhesion to the teeth. We tested whether additional factors are involved in S. mutans sucrose-dependent adhesion. By screening a pVA891-insertion mutant library of S. mutans LT11, we isolated four clones deficient in adhesion to glass in the presence of sucrose, but normal in glucosyltransferase activities. The genetic loci flanking the insertion sites were retrieved and identified. They encode glycerol-3-phosphate dehydrogenase, an ABC transporter, a multidrug-efflux pump, and either the ribulose monophosphate operon or ascorbate metabolism operon. The four mutants were analyzed for their phenotypic expression and in vivo colonization in rats. The multidrug efflux pump mutant failed to colonize the rats. Three other mutants colonized the rats by reverting to the wild type. Therefore, these four factors may contribute to S. mutans sucrose-dependent adhesion.

The microbiology of primary dental caries in humans.

A systematic literature review from 1966 to 2000 revealed 2,730 English-language publications on the role of bacteria in human primary dental caries in vivo. The most pertinent 313 papers were analyzed in evidence tables accessible online (http://www.nidcr.nih.gov). The search targeted all bacterial types implicated previously in caries and asked two questions. First, what is the association of specific bacteria with tooth decay and can causation be attributed to any of those bacteria? Retrieved studies were categorized as randomized-blinded-interventional, longitudinal, case-control, and cross-sectional and were weighted in descending order in terms of significance. Although many studies, due to ethical requirements, had confounding variables, they still indicate strongly: 1) the central role of the mutans streptococci in initiation of caries of smooth surfaces and fissures of crowns of teeth and suggests their potent role in induction of root surface caries; and 2) that lactobacilli are implicated as important contributory bacteria in tooth decay, but their role in induction of lesions is not well supported. Second, what is the source of infection by cariogenic bacteria? Molecular/genetic studies of implicated bacteria isolated from humans, randomized-blinded-interventional, and longitudinal studies indicate that mutans streptococci are spread vertically among humans, mostly from mothers to their children. Implications of these conclusions are briefly discussed. The most significant problems of literature interpretation include the benefits/shortcomings of salivary and plaque monitoring of the flora, the role of sugar(s) in decay as it influences the flora, and modeling strategies to predict lesion score increments as distinct from determination of the etiological role of specific bacteria. Future directions for microbiological clinical caries research are suggested, and the use of the term "caries" to describe the disease, not its lesions, is urged.

Caries inhibition in rats by a sodium fluoride, tripolyphosphate toothpaste with whitening and anti-tartar properties.

The anti-caries properties of a silica-based, sodium fluoride (NaF) toothpaste containing sodium tripolyphosphate (NaTPP) with tooth whitening and anti-tartar properties (Aquafresh Whitening), in specific pathogen-free Osborne-Mendel rats, were assessed in this study. A silica-based, fluoride-free placebo containing NaTPP, and a NaF-containing silica-based USP reference standard toothpaste were used as negative and positive control toothpastes, respectively. Sixty weanling rats were randomly distributed into groups of 20; all were inoculated with S. mutans 10449S, ate cariogenic diet 2000, and drank demineralized water ad libitum. Each toothpaste, packaged in coded tubes, was applied to the dentitions of the rats' teeth for one minute, twice daily on weekdays, and once daily on weekends and holidays. Both the NaF/NaTPP-containing and the NaF-containing USP standard toothpaste groups had lower total enamel caries scores (41 to 45%) than the group treated with the fluoride-free NaTPP-containing placebo. Similar dimensioned differences were evident both at smooth surface and sulcal enamel sites, and in dentinal sites. All were statistically significant at p < 0.001. There were no statistically significant differences at any tooth surface category site between the two fluoride-containing toothpastes' effects. It is thus apparent that Aquafresh Whitening has the anticaries benefit of a USP reference standard NaF toothpaste.

Oral colonization and cariogenicity of Streptococcus gordonii in specific pathogen-free TAN:SPFOM(OM)BR rats consuming starch or sucrose diets.

The significance of Streptococcus gordonii in dental caries is undefined, as is that of other alpha-amylase-binding bacteria (ABB) commonly found in the mouth. To clarify the ecological and cariological roles of S. gordonii our specific pathogen-free Osborne-Mendel rats, TAN:SPFOM(OM)BR, were fed either diet 2000 (containing 56% confectioner's sugar, most of which is sucrose) or diet 2000CS (containing 56% cornstarch, in lieu of confectioner's sugar) and inoculated with S. gordonii strains. Uninoculated rats were free of both indigenous mutans streptococci (MS) and ABB, including S. gordonii, as shown by culture on mitis salivarius and blood agars of swabs and sonicates of dentitions after weanlings had consumed these diets for 26 days. ABB were detected by radiochemical assay using [125I]-amylase reactive to alpha-amylase-binding protein characteristic of the surface of S. gordonii and other ABB. No ABB were detected (detection limit < 1 colony-forming units in 10(6) colony-forming units). Thus the TAN:SPFOM(OM)BR colony presents a 'clean animal model' for subsequent study. Consequently, S. gordonii strains Challis or G9B were used to inoculate weanling rat groups consuming either the high-sucrose diet 2000 or the cornstarch diet 2000CS. Two additional groups fed each of these diets remained unioculated. Recoveries of inoculants were tested 12 and 26 days later by oral swabs and sonication of the molars of one hemimandible of each animal, respectively. Uninoculated animals were reconfirmed to be free of ABB and mutans streptococci, but inoculated ones eating diet 2000CS had S. gordonii recoveries of 1-10% or, if eating diet 2000, 10-30% of total colony-farming units in sonicates. There were no statistically significant differences among the inoculated and uninoculated animal groups' caries scores when they ate the cornstarch diet. Lesion scores for sucrose-eating rats were, however, from 2.4-5.1-fold higher than for cornstarch-eating rats, P < 0.001, and were still higher if animals had been inoculated with either Challis (1.41-fold) or G9B (1.64-fold), than if uninoculated, both P < 0.001, so long as the rats ate the sucrose diet. Therefore, TAN:SPFOM(OM)BR rats do not harbour ABB or S. gordonii but can be colonized by S. gordonii. Colonization levels of S. gordonii on the teeth are higher in the presence of high sucrose than with high starch-containing diets. Caries scores are augmented by sucrose compared with starch, and are further augmented by S gordonii colonization. S. gordonii is thus cariologically significant in the presence of sucrose, at least in this rat.

Caries inhibition in rats by a remineralizing toothpaste.

We tested the anti-caries properties of a prototype remineralizing toothpaste containing sodium fluoride, soluble phosphate and soluble calcium, similar but not identical to Enamelon Toothpaste in specific pathogen-free Osborne-Mendel rats. A fluoride-free placebo and sodium fluoride-containing Crest Regular were used as negative and positive control toothpastes, respectively. Sixty weanling rats were randomly distributed into groups of 20, all were inoculated with S. mutans 10449S, ate diet 2000, and drank demineralized water. Each toothpaste, contained in coded tubes, was applied to the rats' teeth, once for one minute/day, five days/week. There was no difference in bacterial recoveries from tooth swabs among the groups at either the 22- or 37-day post-inoculation recovery date. After rat sacrifice and defleshing, heads were randomly coded and scored blindly for carious lesions according to Keyes/Larson methods. Only after scoring was completed were the random codes broken and the treatment groups identified. Both the Enamelon-like product and Crest Regular treatments resulted in lower total enamel caries scores than the placebo (p < 0.001). The sum of smooth surface scores was also lower for the fluoride-containing toothpastes than for the placebo (p < 0.001). However, the Enamelon-like product had greater caries inhibitory properties than Crest Regular on sulcal and approximal tooth surface categories (p = 0.004 and p = 0.045, respectively). Therefore, the Enamelon-like product had superior caries inhibiting properties compared to Crest Regular at these tooth areas.

Model for assessment of carious lesion remineralization, and remineralization by a novel toothpaste.

This study is of a novel toothpaste which induced remineralization of carious lesions in specific pathogen-free Osborne-Mendel rats. Randomly distributed weanlings in 7 groups (n = 10) each were initially induced to develop carious lesions as a result of a severe dietary and bacteriological challenge. Thus, all were inoculated with S. mutans 10449S, ate diet 2000CS (containing 56% cornstarch) ad libitum, and, upon weaning and for 10 additional days, drank demineralized water supplemented to 10% (w/v) with sucrose (SW) ad libitum. During these 10 days, 6 of the 7 groups of rats were topically treated with a slurried F(-)-free placebo toothpaste. On the 10th day after initial inoculation, two groups were sacrificed, one which had been treated with the placebo and the one which had been untreated. The remaining groups were then provided unsupplemented demineralized water (DW), fed diet 2000CS, and topically treated with either of 5 coded toothpastes: a slurry of the F(-)-free placebo, a similar slurry of a conventional sodium fluoride toothpaste (Crest Regular) containing about 383 ppm F-, or one of three prototype toothpastes formulated by Enamelon, Inc. containing soluble calcium and phosphate salts. Two of these contained 377 ppm F- after mixing their components, either as sodium monofluorophosphate (E-MFP) or as NaF (E-NaF). The third prototype contained 0 ppm F- (E-w/o F). Test items were applied to the dentition for one minute/day, five days/week. These 5 remaining groups were sacrificed 13 days after the DW provision. After defleshing, heads were coded randomly and scored blindly for carious lesions. The exchange of DW for SW was associated with highly significant reductions of 10449S recoveries (p < 0.001), but there were no differences in recoveries among the groups as a function of toothpaste type. Total mandibular and maxillary sulcal and smooth surface caries scores were statistically significantly lower for the E-NaF-treated group at 23 days than for the 23-day placebo-, E-w/o F(-)-, and conventional NaF toothpaste-treated group. Reductions were most impressive quantitatively on approximal tooth surfaces, where both the E-MFP and E-NaF groups had the lowest scores, but were also statistically significant at sulcal surfaces for the E-NaF group. Thus, this study model can be used to detect significant remineralization effects, as occurred with the prototype toothpaste E-NaF.

Current trends of sugar consumption in developing societies.

This paper reviews recent data on sugar consumption in developing countries that may lead to a potential increase in caries prevalence. A search of the business, dental and nutritional literature was conducted through May 1995. There is evidence that sugar (sucrose) use was increasing in China, India, and Southeast Asia. In South and Central America (except Haiti) sugar use was either equivalent to or higher than that in most developed societies. In the Middle East, average sugar use was higher than that of other developing areas. However, it was either lower than or equivalent to the levels reported by other developed countries. Many central African countries consumed less than 15 kg of sugar/ person/year. Of particular concern is a rise in the consumption of sugar-containing carbonated beverages in a number of developing societies: China, India, Vietnam, Thailand, and other Southeast Asian countries are currently major growth markets for the soft drink industry. Consumption of high-sugar desserts and snacks may also be increasing in urban centers in some developing countries. To counteract the potential increase in the prevalence of dental caries in some developing countries, preventive and oral health promotion programs should be planned and implemented. We contend that taxation of sugar-containing products as well as efforts to reduce the level of sugar consumption to "safe" levels may be impractical, and in most countries, cannot be supported for political, economic, or health reasons. Instead, we recommend that collaboration be established between public health authorities and manufacturers/distributors of soft drinks and sweets in developing countries to establish a dental health fund that could be used to support caries preventive programs. The fund could be supported through donations from manufacturers based on the principle of the "milli-cent" (1 cent for every 1000 cents of sales). This minimal contribution would provide enough financial support for planning and implementing dental preventive and restorative programs in developing countries.

A pharmacokinetic and pharmacodynamic study of intravenous pilocarpine in humans.

Pilocarpine (P) is of potential utility in the treatment of xerostomia. Because optimal development of P dosage forms for humans requires that its pharmacokinetics and pharmacodynamics be defined, this intravenous study of its disposition and associated salivary responses was performed. In a hospital setting, two healthy female subjects were given a series of graded doses of intravenous P or placebo to stimulate salivary secretion. Plasma levels of P, heart rate, blood pressure, and respiratory rate were simultaneously monitored. Other objective and subjective physiological parameters were assessed. Plasma concentrations of P declined either mono- or bi-exponentially with time, and brisk initial salivation was followed by prolonged salivation at doses > or = 1 mg. At doses between 0.5 and 3.5 mg, dose-independent pharmacokinetic parameters included a small steady-state volume of distribution (2.4 to 3.0 L/kg), a high plasma clearance (0.026 to 0.03 L/kg/min), and a mean residence time of approximately 100 min. The cumulative volume of whole saliva secreted during the first 3 h post-dose was linearly related to the area under the plasma concentration-time curve. Plasma concentrations from 1 to 42 ng/mL were associated with significant levels of salivation. The pharmacokinetic linearity of the system and proportionality between the area under plasma concentration-time curves and overall salivary response have important implications for the design and utilization of pilocarpine dosage forms.

Helium-neon laser effects on conditioning-induced oral mucositis in bone marrow transplantation patients.

BACKGROUND: Oral mucositis is a common complication of bone marrow transplantation (BMT) conditioning therapy. Sequelae consist of increased risk for infection, moderate to severe pain, compromised oral function, and bleeding. This study investigated helium-neon laser treatment for prevention of conditioning-induced oral mucositis in BMT patients. Patterns and severity of mucositis for specific conditioning drug regimens also were analyzed. METHODS: Twenty patients received laser radiation to their oral mucosa, either left or right of midline. The contralateral side was sham-treated and served as a control. Mucositis severity was scored independently by two modified versions of the Oral Mucositis Index Scale (OMI-A and OMI-B) and the Eastern Cooperative Oncology Group (ECOG) Oral Toxicity Scale; pain severity was scored by subjects on a visual analogue scale (VAS). Cumulative scores were analyzed for differences between the laser-treated and sham-treated sides. RESULTS: Oral mucositis and pain scores were significantly lower for the treated versus the untreated side by OMI-A and B (P < 0.005) and VAS (P = 0.027) criteria, respectively. Ulcerative lesions occurred in all patients bilaterally; severity increased until Day +6, and lesions resolved by Day +21. Mucositis was more severe for patients conditioned with busulfan/carboplatin/thiotepa than for patients conditioned with busulfan/cyclophosphamide/etoposide. CONCLUSIONS: Helium-neon laser treatment was well-tolerated and reduced the severity of conditioning-induced oral mucositis in BMT patients.

Xylitol chewing gum and dental caries.

There is an extensive peer-reviewed literature on xylitol chewing gum as it pertains to effects on tooth decay in human subjects, on human dental plaque reduction, on inhibition of dental plaque acid production, on inhibition of the growth and metabolism of the mutans group of streptococci which are the prime causative agents of tooth decay, on reduction of tooth decay in experimental animals, and on xylitol's reported contribution to the remineralisation of teeth. The literature not only supports the conclusion that xylitol is non-cariogenic but it is now strongly suggestive that xylitol is caries inhibitory, that is, anti-cariogenic in human subjects, and it supplies reasonable mechanistic explanation(s).