The anti-cariogenic potential of xylitol in comparison with sodium fluoride in rat caries experiments

Previous rat caries experiments in our laboratory demonstrated an anti-cariogenic and most probably a remineralizing effect of xylitol. The purpose of the present study was to compare the caries-inhibiting property of xylitol and fluoride in drinking water. The study consisted of two experiments with Osborne-Mendel rats, superinfected with S. mutans. In the first experiment, the rats were fed ad libitum a cariogenic diet containing 20% sucrose and 5% glucose (diet SSP 20/5) and tap water containing 0%, 2%, or 4% xylitol. An additional control group was fed diet SSP 20/5 supplemented with 5% xylitol. In the second experiment, the rats were also fed diet SSP 20/5, but received tap water, demineralized water (both containing less than 0.1 ppm F-), or tap water containing 10 and 40 ppm fluoride. Some animals in the 4% xylitol drinking water group showed a mild osmotic diarrhea for the first four days and a retarded increase in body weight of limited duration. S. mutans colonized to a similar level in all groups of both experiments. Fluoride as well as xylitol in the drinking water reduced the fissure caries scores significantly. However, 10 and 40 ppm fluoride had a more pronounced inhibiting effect on the caries experience than did 4% xylitol in the drinking water or 5% xylitol in the diet.     

The effects of sucralose, xylitol, and sorbitol on remineralization of caries lesions in rats.

The purpose of this study was to determine whether ingestion of sucralose, xylitol, sorbitol, or distilled water alone could enhance remineralization of early caries lesions in rats. Rats were infected by Streptococcus sobrinus, fed diet 2000 (Ziegler Brothers, Gardners, PA) ad libitum for two weeks, and, in addition, were offered drinking water sweetened by sucrose (10% w/v). A group of rats terminated at this time displayed significant levels of sulcal and smooth-surface caries. The remaining animals, for the ensuing three weeks, either continued on the same cariogenic challenge or received their essential nutrition by gavage and drank water, sweetened by one of the agents listed above, ad libitum. At the end of the additional three-week period, animals receiving sucralose, xylitol, sorbitol, or distilled water had fewer lesions than did the animals terminated after the two-week cariogenic challenge. The results show that removal of the cariogenic challenge allowed remineralization to occur and that no sweetening agent was superior to another in this respect.     

Effects of xylitol on survival of mutans streptococci in mixed-six-species in vitro biofilms modelling supragingival plaque

Xylitol has been claimed to reduce mutans streptococci (MS) in dental plaque by energy-consuming futile metabolic cycles. This study aimed to investigate the effects of xylitol on MS in an in vitro 6-species oral biofilm model. Each multispecies biofilm contained either a laboratory reference strain, a fresh isolate, a xylitol-sensitive or a xylitol-resistant strain of Streptococcus mutans or Streptococcus sobrinus. Biofilms, grown on pellicle-coated hydroxyapatite discs, were fed with a glucose/sucrose-supplemented medium 3 times daily for 45 min and incubated in saliva between feedings. Before or after feeding, biofilms were exposed to either 7.5% xylitol, 7.5% sorbitol or to saliva (control) for 20 min. After 64.5 h, biofilms were harvested and the microbial composition was analysed by non-selective and selective culturing. Strain variability in the ability to colonize biofilms was observed. However, the response patterns in the biofilms to the 4 polyol treatments were similar. None of the MS were inhibited by xylitol provided either before or after feeding. Sorbitol given before feeding did not affect microbial growth whereas sorbitol provided after feeding showed a slight, albeit statistically significant increase in MS counts for some of the tested strains. It did so at the expense of Streptococcus oralis, which decreased in numbers. The present findings do not support the contention that xylitol reduces MS in plaque by futile metabolic cycles.     

Effect of long-term, peroral administration of sugar alcohols on man

Certain sugar alcohols (polyols), notably mannitol, sorbitol and xylitol have gained use in food manufacturing for sweetening and technical purposes. These compounds are natural polyols that occur in small amounts in animals and plants. Some sugar alcohols, like xylitol, appear as normal intermediates in the carbohydrate metabolism. Exogenous mannitol, sorbitol and xylitol are metabolized in the human body along pre-existing, physiological pathways. Moderate doses of least xylitol and sorbitol are almost totally absorbed and metabolized, chiefly in the liver cells, thereby eventually contributing to the formation of glucose and liver glycogen. Various slowly absorbed carbohydrates, including sugar alcohols, when taken in orally in large quantities, can give rise to osmotic diarrhea. The available data indicate that the severity of such gastro-intestinal disturbances, induced by large doses of polyols, decrease in the following order: mannitol, sorbitol, xylitol. This osmotic diarrhea resembles that caused by lactose in subjects with restricted or frank lactose intolerance. The quantities of xylitol, for example, required to elicit diarrhea are so high that the consumption of xylitol for dental purposes does not cause any problems in children or adults. Long-term feeding trials and peroral loading experiments on human subjects have been unable to show any clinically significant differences between chronic users of xylitol and comparative human material in factors related to various metabolic functions of the body. These subjects have not shown any delayed or acute reactions which could be distinguished from those caused by the consumption of a sucrose diet. The available clinical data generally suggest that moderate consumption of the above polyols is not harmful to human metabolism.     

The optimum time to initiate habitual xylitol gum-chewing for obtaining long-term caries prevention

Habitual xylitol gum-chewing may have a long-term preventive effect by reducing the caries risk for several years after the habitual chewing has ended. The goal of this report was (1) to determine if sorbitol and sorbitol/xylitol mixtures provide a long-term benefit, and (2) to determine which teeth benefit most from two-year habitual gum-chewing - those erupting before, during, or after habitual gum-chewing. Children, on average 6 years old, chewed gums sweetened with xylitol, sorbitol, or xylitol/sorbitol mixtures. There was a "no-gum" control group. Five years after the two-year program of habitual gum-chewing ended, 288 children were re-examined. Compared with the no-gum group, sorbitol gums had no significant long-term effect (relative risk [RR], 0.65; 95% confidence interval [c.i.], 0.39 to 1.07; p < 0.18). Xylitol gum and, to a lesser extent, xylitol/sorbitol gum had a long-term preventive effect. During the 5 years after habitual gum-chewing ended, xylitol gums reduced the caries risk 59% (RR, 0.41; 95% c.i., 0.23 to 0.75; p < 0.0034). Xylitol-sorbitol gums reduced the caries risk 44% (RR, 0.56; 95% c.i., 0.36 to 0.89; p < 0.02). The long-term caries risk reduction associated with xylitol strongly depended on when teeth erupted (p < 0.02). Teeth that erupted after 1 year of gum-chewing or after the two-year habitual gum use ended had long-term caries risk reductions of 93% (p < 0.0054) and 88% (p < 0.0004), respectively. Teeth that erupted before the gum-chewing started had no significant long-term prevention (p < 0.30). We concluded that for long-term caries-preventive effects to be maximized, habitual xylitol gum-chewing should be started at least one year before permanent teeth erupt.     

Effect of xylitol on dentin formation in molars of adult rats

A xylitol-induced reduction in dentin formation has been observed in molars of post-weanling rats, but the effect in older animals with a slower rate of secondary dentinogenesis has not been investigated. We examined the effects of different concentrations of dietary xylitol on dentinogenesis in molars of young adult rats. The control group received a commercial basal diet, while for the other 3 groups, the same diet was supplemented with 5. 10 and 20% of xylitol. After 8 weeks, dentin thickness beneath the main fissures in the mandibular 1st and 2nd molars was measured. The final body weights did not differ between the groups. Dentin formation in the 1st molars of the 10 and 20% xylitol groups was significantly lower as compared to the controls, whereas no difference was found between these 2 groups. In conclusion, dietary xylitol reduces dentin formation in young adult rats in spite of the slow rate of dentinogenesis.     

Caries-preventive effect of dentifrices containing various types and concentrations of fluorides and sugar alcohols

The caries-inhibiting effect of unsupervised daily use of four different toothpastes was compared in a 3-year clinical and microbiological study: (1) 0.8% sodium monofluorophosphate (MFP) with 3% xylitol and 6% sorbitol; (2) 0.03% sodium fluoride with 3% xylitol and 6% sorbitol; (3) 0.8% MFP with 9% sorbitol, and (4) 0.03% sodium fluoride with 9% sorbitol. In all 284 children, 12-13 years old at baseline, took part in the study. After 3 years, no statistically significant differences were found between the different toothpaste groups concerning either development of initial or gross caries lesions or number of mutans streptococci and lactobacilli in saliva. However, children with no detectable approximal caries at baseline, who used the MFP toothpaste with the xylitol-sorbitol mixture, showed a lower (p less than 0.05) caries increment as compared with children who used the MFP toothpaste with sorbitol alone.     

Dental effects of xylitol compared with other carbohydrates and polyols in the diet of laboratory rats

Xylitol at 10 and 20 per cent disturbed gastro-intestinal function but was tolerated better than sorbitol or mannitol. Toleration improved when dietary polyol levels were increased gradually to a maximum of 20 per cent. Twenty per cent of xylitol in the diet replacing that amount of sucrose reduced the level of caries, but 20 per cent of wheat starch was equally effective. Ten per cent of xylitol in place of sucrose produced as much caries as the basic cariogenic diet, but xylitol at a level of 2 per cent was associated with an increase in caries. There was no confirmation of an active caries-reversing effect of xylitol when xylitol-containing diets were alternated with the basic high-sucrose cariogenic ration.     

Cariogenicity of frequent aspartame and sorbitol rinsing in laboratory rats

The cariogenicity of frequent rinsings with aspartame and sorbitol was studied in the rat caries model with animals randomly assigned to four oral rinse groups (16 rats/group): 0.05% aspartame, 20% sorbitol, deionized distilled water, and 20% sucrose; all solutions at pH 3.0. After rinsing five times daily for 21 days, mandibular molars were scored for caries. Smooth surface, proximal and morsal caries scores did not differ significantly between groups. Moderate dentinal sulcal caries for the sucrose group was significantly greater than in the aspartame, sorbitol, and water groups (p less than 0.05). Rinsing with 0.05% aspartame (similar in pH and concentration to that found in carbonated beverages) or sorbitol did not potentiate caries activity.     

The effect of sugar alcohols on plaque and saliva level of Streptococcus mutans

The usage of sucrose substitutes such as polyols in snack-type foods is a logical and practical means of reducing caries incidence without perturbing normal dietary eating patterns. S. mutans and L. casei can ferment mannitol and sorbitol, but are inactive towards xylitol. This ability of these cariogenic organisms to ferment the hexitols does not seem to be of concern when gums containing them are used at the normal rate. However, when hexitol gum usage is excessive, the S. mutans levels may increase. In contrast to the hexitols, excessive usage of gums sweetened with xylitol caused a significant decrease in the levels and proportions of S. mutans in saliva and plaque. While this effect on S. mutans may be an indirect one, this finding provides added evidence for the superiority of xylitol as a sucrose substitute in dentistry.     

Effects of xylitol and carbohydrate diets on dental caries, dentine formation and mineralization in young rats

Female Wistar rats were weaned at the age of 3 weeks and fed for 7 weeks either a high-sucrose diet, a non-cariogenic raw potato-starch diet, a high-sucrose diet with 5% xylitol supplement, a raw potato-starch diet with 5% xylitol supplement or a non-cariogenic, commercial, powdered rat food (Ewos R3) for reference. A low xylitol concentration reduced the progression and severity of carious lesions but did not affect dentine apposition or the width of predentine in rats fed high-carbohydrate diets. Widening of the predentine zone in rats fed a high-sucrose diet might reflect disturbed mineralization, which could not be explained by serum ionized calcium or phosphate ion levels and which could not be corrected by low xylotol concentrations. It is concluded that the reduced area of dentinal carious lesions after low xylitol supplementation is not dependent on dentine formation or mineralization, but rather on direct effects in the mouth.     

Studies of the dental properties of lactitol compared with five other bulk sweeteners in vitro

Standardized mixed cultures of dental plaque microorganisms were incubated for 24 h in media containing six different bulk sweeteners as energy source. The attack of the acid generated on tooth mineral was measured by calcium and phosphorus analyses. Demineralization was most severe with glucose and sucrose. Less acid was generated from sorbitol and mannitol, with much reduced demineralization. Fermentation of lactitol and xylitol was only very slight, leaving the final pH high and leading to extremely low enamel demineralization figures. The amounts of polysaccharide synthesized by the microorganisms in the incubations decreased in the order: glucose greater than sucrose greater than sorbitol greater than mannitol greater than lactitol greater than xylitol.     

Initial catabolism of sorbitol in Actinomyces naeslundii and Actinomyces viscosus

The initial steps of sorbitol catabolism were studied in 4 strains of Actinomyces naeslundii and Actinomyces viscosus that had been isolated from human dental plaque. Cell-free extracts were prepared from cells grown in the presence of either sorbitol, xylitol or glucose. The extracts from all strains grown on sorbitol had nicotinamide adenine dinucleotide-linked dehydrogenase activities for sorbitol and xylitol and reduced nicotinamide adenine dinucleotide-linked reductase activities for fructose and xylulose. Two of the strains also exhibited these activities when grown in the presence of xylitol, and all glucose-grown cells lacked them. The results indicate that sorbitol metabolism in oral actinomyces involve oxidation of sorbitol to fructose by an inducible enzyme, nicotinamide adenine dinucleotide-linked sorbitol dehydrogenase. This step is followed by the phosphorylation of fructose with guanosine triphosphate as a main phosphoryl donor. Thus, the initial catabolic pathway of sorbitol in A. naeslundii and A. viscosus is different from those described for other oral bacteria.     

Does the presence of xylitol in a sorbitol-containing chewing gum affect the adaptation to sorbitol by dental plaque?

It is known that xylitol inhibits sorbitol metabolism in some bacteria in vitro. The effect of xylitol/sorbitol-containing chewing gum on sorbitol adaptation of dental plaque was therefore examined. Ten subjects used this chewing gum for 12 wk, and plaque was collected before (control plaque) and after (test plaque) the exposure to sorbitol/xylitol. The metabolism of sorbitol by the plaque was examined with ^l4C-labeled sorbitol, and the radioactive metabolites were detected by high-performance liquid chromatography (HPLC). A considerable individual variation in acid formation was found. The mean values of total acids in the test plaque increased, as compared with the control plaque. An adaptation of dental plaque to sorbitol thus occurred in spite of the presence of xylitol in the chewing gum. The concentration of acetic acid predominated over other acids in both the control and test plaques. The proportions of acids expressed in percentage of total acids differed only slightly. Thus, long-term use of xylitol/sorbitol-containing chewing gum did not eliminate the adaptation of dental plaque to sorbitol.     

In vivo measurements of sulcal plaque pH in rats after topical applications of xylitol, sorbitol, glucose, sucrose, and sucrose plus 53 mM sodium fluoride

In two series of experiments, Sprague-Dawley-derived rats were infected orally with cariogenic micro-organisms and fed caries-promoting diets. By means of an antimony electrode, resting pH values were measured in the mesial sulcus of the maxillary left first molar. 100 or 200 microL of the test solutions were applied, and the change in pH (delta pH) was recorded for three min. Test solutions were: (a) 10% sucrose, 10% glucose, 10% sorbitol, or 10% xylitol; (b) 0%, 10%, 20%, or 40% sucrose; (c) 0%, 3%, 7%, or 10% sucrose; and (d) 10% sucrose, 10% sucrose + 53 mmol/L NaF (1000 ppmF-), or 10% sucrose + 53 mmol/L NaCl. Experimental design was a 4 X 4 Latin square (a, b, c) or a cross-over design (d). Solutions of sucrose and glucose gave significantly greater decreases in pH than did sorbitol or xylitol. pH fall was maximal for 10% sucrose and significantly less for 40% sucrose during the three-minute experimental period. For sucrose solutions ranging in concentration from 3 to 10%, pH fall was highest after application of 10% sucrose when plaque was previously rinsed with water, but this pH fall did not differ significantly from that obtained using a 7% sucrose solution. Adding 1000 ppmF- to a 10% sucrose solution caused an increase in pH. Rinsing the teeth to remove saliva resulted in significantly lower resting pH values. The results of these experiments are in agreement with the results of human plaque pH measurements.     

Interaction between xylitol and sorbitol in plaque metabolism

Xylitol and sorbitol, when metabolized by microorganisms, are transported through the cell membrane and phosphorylated by membrane-bound phosphoenolpyruvate-dependent phosphotransferase systems. Sorbitol-6-phosphate may be oxidized by a sorbitol-6-phosphate dehydrogenase to fructose-6-phosphate and further decomposed in the Embden-Meyerhof pathway. Xylitol-5-phosphate - if not metabolized - may be toxic to the cell. There are few specific pathways known for xylitol metabolism in microorganisms. Due to structural resemblance between the xylitol and the sorbitol molecules interaction between xylitol and sorbitol metabolism is likely to occur. Xylitol - although only slowly taken up by plaque and oral microorganisms - may reduce plaque formation and cause an increase in plaque pH. Evidence for a phosphotransferase system for xylitol has recently been demonstrated in Strep. mutans, which may cause accumulation of xylitol-5-phosphate in the cell. Some studies carried out by the author and associates on acid production in the oral cavity from cell. Some studies carried out by the author and associates on acid production in the oral cavity from sorbitol in the presence of xylitol in chewing gum containing sorbitol reduces acid production from sorbitol. This may be explained by the following effects of xylitol: Reduction of plaque and the number of microorganisms on the teeth. This is thought to be a consequence of the toxic effect of xylitol-5-phosphate. Inhibition of acid production from sorbitol. This is believed to be a consequence of competitive blocking of the phosphotransferase system due to structural similarities between xylitol and sorbitol.     

Effects of xylitol, sorbitol and fluoride mouthrinses on glucose clearance in adolescents

The present work describes and analyzes the results of a randomized clinical trial on 98 healthy adolescents (age 18 +/- 0.7 years) in order to evaluate the effects of a 14 days treatment with mouthrinses containing xylitol (0.2%; 0.5% and 1%), sorbitol (1%), NaF (0.1% respectively) on salivary glucose clearance. In all volunteers oral glucose clearance followed an exponential curve as a function of time, which fitted almost exactly to the equation log Ct = log Co - bt from 1 to 16 minutes after sugar rinsing. Xylitol treatment provoked an increase in oral glucose clearance, which was proportional to its concentration in the mouthrinse formula. The average AUC (area under curve) decrease was 9.1% in subjects rinsing with 0.2% xylitol; 21.5% with 0.5% xylitol and 40.0% with 1% xylitol. 1% sorbitol or 0.1% NaF did not modify any of the pharmacokinetical parameters over the same treatment time. The mouthrinses containing 1% xylitol and 0.1% NaF produced the same results as 1% xylitol alone on oral glucose clearance. No significant changes in the salivary flow rate nor in oral health parameters were observed concomitant to the faster oral glucose clearance by xylitol treatment. Since the sugars salivary clearance is part of a process intended to prevent dental caries, our results suggest that xylitol adds another mechanism of action to its well known cariostatic and anticaries properties.     

The effect of non-cariogenic sweeteners on the prevention of dental caries: a review of the evidence.

The role of sugar substitutes such as xylitol and sorbitol in the prevention of dental caries has been investigated in several clinical studies. The purpose of this report is to review the current published evidence regarding the relationship between sugar substitutes and dental caries. A literature search was conducted using MEDLINE and EMBASE and included studies published from 1966 to 2001. Studies that included human subjects and were published in English were included in this review. A total of fourteen clinical studies were reviewed that evaluated the effect of sorbitol or xylitol or the combination of both sugar substitutes on the incidence of dental caries. Most of the reports were of studies conducted with children outside of the United States. These studies demonstrated a consistent decrease in dental caries, ranging from 30 to 60 percent, among subjects using sugar substitutes as compared to subjects in a control group. These caries rate reductions were observed in subjects using xylitol or sorbitol as the sugar substitute in chewing gum or toothpaste. The highest caries reductions were observed in subjects using xylitol. These findings suggest that the replacement of sucrose with sorbitol and xylitol may significantly decrease the incidence of dental caries.     

Effects of 3 months frequent consumption of hydrogenated starch hydrolysate (Lycasin), maltitol, sorbitol and xylitol on human dental plaque.

Lozenges containing hydrogenated starch hydrolysate (Lycasin), maltitol, sorbitol or xylitol were consumed 4 times daily during 3 months by 4 groups of persons (in all 85 subjects). In the maltitol-, sorbitol- and xylitol-group the plque wet weights were of the same magnitude before and after the test period. In the Lycasin-group, a higher value was found after than before the 3-month period (p less than 0.01). The acid production in suspensions of dental plaque material from Lycasin, maltitol and sorbitol expressed as per cent of that from glucose was approximately the same before and after the test period. From xylitol no acid production could be demonstrated either before or after the 3-month period. There were no statistically significant differences between the plaque pH-changes induced by rinsing with 50% solutions of Lycasin, maltitol, sorbitol or xylitol before and after the test period. However, there was a tendency (p less than 0.05) towards lower pH-values induced by the maltitrol and sorbitol rinse after the 3-month period compared with before. No difference in the relative numbers of facultative anaerobic streptococci. Streptococcus mutans or facultative anaerobic lactobacilli before and after the test period was found.     

Effect of dentifrices containing either xylitol and glycerol or sorbitol on mutans streptococci in saliva.

In 76 adults, randomly distributed between two groups, a comparison was made of the effect on the level of mutans streptococci in saliva between two dentifrices containing: (1) xylitol (9.9%) and glycerol (20%) or (2) sorbitol (28%) as humectants. After the use of the dentifrices twice daily for 3 months, the levels of mutans streptococci had not changed significantly in the sorbitol-treated group, whereas a significant reduction (p less than 0.0005) was found in subjects using the xylitol/glycerol dentifrice. The difference between the two dentifrice groups based on the changes observed during the 3-month period was also significant (p less than 0.02).