Recent results of randomized trials testing the efficacy of xylitol in caries prevention have been conflicting. This narrative review reveals the sources of discrepancy. The following databases were searched for the terms “xylitol” or “artificial sweeteners” restricted to the English language: PubMed, Web of Science, Evidenced-Based Medicine, Scopus, and the Cochrane database. In a separate search, the terms “dental caries” or “cariogenicity” or “glucosyltransferase” or “low glycemic” or “low insulinemic” or “dysbiosis” or “gut microbiome” were used and then combined. In section I, findings regarding the role of xylitol in dental caries prevention, the appropriateness of research methods, and the causes for potential biases are summarized. In section II, the systemic effects of xylitol on gut microbiota as well as low-glycemic/insulinogenic systemic effects are evaluated and summarized. The substitution of a carbonyl group with an alcohol radical in xylitol hinders its absorption and slowly releases sugar into the bloodstream. This quality of xylitol is beneficial for diabetic patients to maintain a constant glucose level. Although this quality of xylitol has been proven in in vitro and animal studies, it has yet to be proven in humans. Paradoxically, recent animal studies reported hyperglycemia and intestinal dysbiosis with artificial sweetener consumption. Upon careful inspection of evidence, it was revealed that these reports may be due to misinterpretation of original references or flaws in study methodology. Any systemic benefits of xylitol intake must be weighed in consideration with the well-established adverse gastrointestinal consequences. The contribution of xylitol to gut dysbiosis that may affect systemic immunity warrants further research.

Obstacles in the Quantification of Caries Activities

Although xylitol is widely believed to have anticariogenic properties [Mäkinen et al., 1996b], the scientific evidence quantifying the reduction in caries incidence is sparse. This impediment is due to the time lapse in the emergence of dental caries after cariogenic exposure [de Paola and Alman, 1972] and the reversible nature of de- and remineralization of dental enamel. Although some studies had a long enough duration to observe cariogenicity [Sintes et al., 1995; Mäkinen et al., 1996a; Sintes et al., 2002; Mäkinen et al., 2005], various methodological deficiencies make it difficult to conclusively determine the efficacy of xylitol in caries prevention. Furthermore, many factors affect cariogenicity, including the acidogenic potential of fermentable carbohydrates, alterations in salivary flow, frequency, and type of carbohydrate exposure, stickiness of carbohydrates, and oral hygiene self-care [DePaola et al., 1989]. Unfortunately, confounding factors such as oral self-care practice, diet characteristics, and fermentable carbohydrate exposure frequency have not been controlled for in any of the studies evaluating the anticariogenic effect of xylitol.

To offer as evidence for causality, only original research in longitudinal or intervention studies should be considered as scientific proof. Thus, reviews or expert opinions were not included. To date, many studies have substantial shortcomings such as poor evidence of causal direction and absence of an appropriate control group. Nevertheless, others listed studies that used no or inappropriate controls as strong evidence for the anticariogenicity of xylitol [Maguire and Rugg-Gunn, 2003]. Most well-conducted reviews reported the evidence of “poor quality” without critical assessment of the methodology or the deficiencies thereof. Clear delineation of deficiencies in each study will expand our scientific understanding and knowledge.

Low- or anticariogenicity of xylitol can be attributable to its passive substitution of fermentable carbohydrates [Van Loveren, 2004] and subsequent reduction of acidogenic potential [Bradshaw and Marsh, 1994], increased salivary flow [Dowd, 1999], and inhibition of cariogenic Streptococcus mutans [Vadeboncoeur et al., 1983; Trahan et al., 1985]. However, a recent research trend testing xylitol as an active caries suppressor resulted in many null results.

Methodologic Issues in Caries Research

Several randomized trials in children reported reduced caries activities after intervention with xylitol, but the study designs and executions were fraught with deficiencies and biases. In multigroup comparison analyses such as in ANOVA, one group (for example, no chewing gum group) can result in a highly significant p value. To avoid biases such as this, if the intervention is chewing xylitol gum, increased salivary flow due to the mechanical action of chewing has to be controlled by employing chewing gum base without the active ingredient as a reference. Not using any gum as a comparator group will bias the results as shown in one study [Mäkinen et al., 1995]. Nevertheless, this study has been quoted as the largest study with a positive impact of xylitol chewing gum on dental caries.

If xylitol wipes were used as an intervention, the control group should employ wipes without xylitol, to eliminate bias from the mechanical removal of biofilm by wiping [Zhan et al., 2012]. Wiping action with different forces will also generate another bias. Additionally, if the outcome was measured by dmfs or dmft in the mixed dentition, missing teeth due to natural exfoliation might have a different rate of caries, and this will bias the results.

A recent elaborate trial in adults resulted in a null result due to using a control that has similar anticaries action [Bader et al., 2013]. This study employed as a reference group sucralose, which also inhibits glucosyltransferase in S. mutans [Bowen and Pearson, 1992; Bowen, 2013]. Thus, both experimental and control groups used low-cariogenic sweeteners which decreased the contrast between the groups [Smith et al., 1979; Devulapalle and Mooser, 2001]. For the same reason, comparing xylitol-containing toothpaste to sorbitol-containing toothpaste did not generate a significant reduction in dental caries in children [Chi et al., 2014]. As expected, the contrast between xylitol and other low-cariogenic sweeteners such as sucralose or sorbitol was not significantly different. We recognize the ethical dilemma of not employing sucrose as a control group because it has been proven to be cariogenic in humans. Nevertheless, using other low-cario-genic controls will diminish the difference between the groups and result in a nonsignificant anticaries action of xylitol. This will generate the impression that xylitol has no anticariogenic action, which may not be correct.

To determine statistically significant differences in this kind of trial, the changes from baseline to the study end in the experimental group must be compared to the changes in the control group. Unfortunately, many trials compared only the values after the test. As shown in Figure 1 (simulated data), if only posttreatment values are compared, it appears the xylitol group has lower caries activities. However, if using the correct method of comparing the changes from baseline in the two groups, the results will not be significant, because the two groups are exactly parallel, which means the intervention did not bring any changes. In a recent trial, xylitol-containing chewing gum plus oral health education was compared to oral health education alone among hearing- and vision-impaired children. The results showed the significant anticaries and antiplague effects of xylitol-containing chewing gum use. However, this study may also be biased because the study ignored the chewing-related salivary flow increase and its cleansing action [Watthanasaen et al., 2017]. Notably, chewing gum may not be an appropriate intervention for the elderly population who commonly have temporomandibular dysfunction [Nguyen et al., 2018].

Fig. 1.

Salivary glucose levels in the xylitol chewing gum and control groups (simulated data). Simulated diagram showing the statistical knowledge requirement in intervention trials.

Fig. 1.

Salivary glucose levels in the xylitol chewing gum and control groups (simulated data). Simulated diagram showing the statistical knowledge requirement in intervention trials.

Close modal

Superiority of Xylitol over Other Sugar Alcohols

To demonstratethesuperiority of xylitol over other low-cariogenic sweeteners, the results must show a significant decrease in caries incidence in the xylitol group. However, xylitol was superior in one study [Splieth et al., 2009], and sorbitol was superior in another [Wennerholm and Emilson, 1989]. Comparing erythritol/maltitol versus xylitol/maltitol (which is basically comparing erythritol to xylitol because maltitol is constant in both groups) did not result in caries reduction [Lenkkeri et al., 2012]. All these conflicting results brought skepticism regarding the anticariogenicity of xylitol in the public’s view. However, the meta-analysis by Deshpande and Jadad [2008], which we did not include in our review because it is not an original research, reported that that chewing gums containing xylitol decreased caries rate by 58.7% and those containing sorbitol by 20%. However, their results did not account for caries reduction due to salivary flow or mechanical stimulation of chewing-related anticariogenicity and, thus, may be biased [Deshpande and Jadad, 2008].

Perhaps, it is useful to define “anticariogenicity” here as “any process that decreases caries experience.” Anticariogenicity in this context includes fluoride application, Listerine mouth rinse, chlorhexidine rinse, and increased salivary flow. Xylitol decreases caries by inhibiting glucosyltransferase which blocks glucose utilization by S. mutans and their adhesion to the tooth surface. The anticariogenicity of xylitol chewing gum, however, is the combined effect of glucosyltransferase-related anticario-genicity plus chewing-related anticariogenicity. Thus, to prove the pure anticaries action of xylitol, the control group must chew similar gum base without xylitol.

Cariogenic Bacteria Quantification

Several studies quantified S. mutans or Streptococcus mitis when xylitol was consumed. Significantly decreased S. mutans in the saliva was observed with xylitol consumption [Wennerholm et al., 1994]. However, sugar restriction also decreased the level of S. mutans indicating that the inhibition of S. mutans is a passive suppression via sugar depletion [Wennerholm et al., 1995]. Meanwhile, consumption of xylitol-containing snacks and candy did not reduce S. mutans levels [Roberts et al., 2002]. The S. mutans quantification may assume that S. mutans is the leading cariogenic microbe. In reality, Lactobacillus spp. and Actinomyces could also contribute to caries development [Brailsford et al., 1999; Beighton, 2005; Caufield et al., 2007; Thabuis et al., 2013]. However, all these microbes could be innocent bystanders that tolerate low pH generated by fermentation of carbohydrates and may not be causative agents for caries [Beighton, 2005]. This bystander theory can be corroborated by the fact that their numbers and pH-lowering potential were not statistically different between caries-prone groups and groups that are not caries prone [Sansone et al., 1993].

Maternal Transmission of Cariogenic Bacteria to Children

Several groups examined mother and child pairs assessing the maternal xylitol consumption and transmission of bacteria to their child in randomized trials. When the child is newly born, the mother’s immunity may affect the neonate’s immunity. But after 6 months, when the child starts eating solid foods, the mother’s xylitol gum chewing may have a very little impact on the child’s oral microbiome. It is well known that the microbial community evolves with the available substrates and the diet, as shown in the gut microbiome [David et al., 2014; Vieira et al., 2014] as well as in the oral cavity [Ribeiro et al., 2017]. Interestingly, the time frame of solid food introduction coincided with the reported colonization of S. mutans in 20% of infants aged 6–9 months [Mohan et al., 1998]. Nevertheless, several studies reported a potentially spurious correlation of maternal xylitol consumption with offspring dental caries incidence [Isokangas et al., 2000; Söderling et al., 2001]. Meanwhile, others did not find any such protective action of maternal xylitol consumption on children’s caries activities [Thorild et al., 2004; Hanno et al., 2011]. Also, 50% of children in the low-S. mutans group were cared for by persons other than the mother suggesting that the S. mutans level might have been linked to the diet shared by mother and child [Caufield et al., 1993]. The child’s inoculation of oral S. mutans is multifactorial. It has been proven that age, number of teeth, and bottle with sugared beverage usage were all related to the emergence of S. mutans in the child’s oral cavity [Mohan et al., 1998].

Comparison of Xylitol to Fluoride Products

It has been reported that the low acidogenicity of xylitol may aid subsequent low-cariogenic action as a “passive process of substituting sugar or other fermentable carbohydrates” [Imfeld, 1993]. A clear reduction of fermentation of xylitol compared with natural glucose, sucrose, and fructose has been shown in vitro, and xylitol did not lower the pH below the critical value of 5.5 [Splieth et al., 2009; Almståhl et al., 2013]. Some early studies, however, did not observe any changes in the acidogenic potential with xylitol mouth rinse in comparison to fluoride rinse [Giertsen et al., 1999]. This study has proven that anticariogenicity of xylitol mouth rinse is not superior to fluoride rinse.

Several recent randomized trials exhibited better methodologic quality, and yet results were conflicting [Zhan et al., 2012; Lee et al., 2015]. Lee et al. [2015] reported that “Xylitol consumption did not have an additional benefit over fluoride treatment.” In 2012, Zhan et al. enrolled 6- to 35-month-old children (n = 44) and randomly assigned them to xylitol wipes or wipes without active ingredients. At the end of the study (12 months), they observed “significant reduction in new caries in xylitol wipes group” but “no significant differences were observed in levels of mutans streptococci and lactobacilli at all time-points between the two groups” [Zhan et al., 2012]. However, the imbalance in maternal snacking patterns and the force of wiping biofilm could have biased the results of this trial. Randomization may not balance all risk factors when the sample size is small [Rothman, 1977].

Another recent trial among adults reported a significant decrease in incipient dental caries and progression of the same in the xylitol chewing gum group compared with the group that chewed gum sweetened with a combination of isomalt, sorbitol, mannitol, and maltitol for 1 year [Cocco et al., 2017]. Unlike in the previous study [Bader et al., 2013], Cocco et al. [2017] prohibited other dental caries-limiting activities such as fluoride treatment during the experiment, except for personal oral hygiene practices, but we question the ethical basis for this prohibition. They reported a significantly lower caries increment with xylitol chewing gum use for 1 year compared with polyol gum use. Their overall results should read “The comparison between the two follow-up evaluations (12 and 24 months from baseline) showed no statistically significant differences between the two groups” but xylitol gum chewing showed slightly lower dental caries experience in the severe-caries group. However, gum chewing may be contraindicated in older adults to avoid temporomandibular dysfunction [Tabrizi et al., 2014; Nguyen et al., 2018].

Concluding Remarks

The relationship of xylitol with dental caries can be summarized as follows:

The evidence that chewing gum containing xylitol is superior to chewing sugared gum is reasonably strong with relatively little bias [Scheinin et al., 1975].

The evidence for the mechanism that xylitol suppresses dental caries via inhibition of glucosyltransferases in cariogenic bacteria is reasonably strong [Devulapalle and Mooser, 2001; Bowen and Koo, 2011]. However, sorbitol and sucralose also demonstrated similar anticariogenic effects in animal models [Bowen and Pearson, 1992].

The evidence regarding low acidogenicity of xylitol is sufficiently strong [Marsh et al., 1992; Almståhl et al., 2013].

The evidence for superior noncariogenicity of xylitol over other sugar alcohols is not sufficient. Several studies reported that erythritol may be comparable [Thabuis et al., 2013] or superior to xylitol in caries inhibition [Falony et al., 2016]. However, many of these studies were conducted in children with mixed dentition where missing teeth might have different rates of caries, and this information was not considered. Thus, the missing teeth would have biased the results.

The evidence is insufficient to support the thesis that the anticariogenic effect of xylitol is comparable to fluoride or chlorhexidine [Giertsen et al., 1999]. However, some large-scale trials in school children reported improved anticaries action of toothpaste with added xylitol in addition to fluoride [Sintes et al., 1995, 2002]. However, the outcome which ignored caries activities in missing teeth could have biased the results.

The evidence regarding whether xylitol promotes remineralization is equivocal. In 2 in vitro studies, one study result supports the remineralization capability of xylitol [Cardoso et al., 2014] while the other does not [Shen et al., 2017]. In the former study, the remineralization was observed in conjunction with fluoride plus xylitol. Thus, the independent action of xylitol on remineralization cannot be determined.

The evidence regarding maternal xylitol consumption preventing children’s dental caries is highly spurious. Other prenatal nutrients (for example, vitamin D) could influence the enamel strength and subsequent dental caries susceptibility [Schroth et al., 2014]. Thus, attributing lower dental caries incidence in children solely to maternal xylitol consumption is overly simplistic.

In summary, xylitol may be useful as a low-cariogenic sweetener [Fontana and González-Cabezas, 2012], and this benefit is from passively replacing fermentable sugar [Imfeld, 1993]. Additionally, some systemic adverse effects must be considered before recommending wider xylitol use. These systemic effects of xylitol consumption will be discussed in the next section.

Xylitol and Low-Glycemic Effects

In 1986, the United States Food and Drug Administration declared xylitol as safe for human use. Since then, it has been registered as “generally safe” for utilization in foods, pharmaceuticals, and oral health care products in many countries. Generally, safe amounts of xylitol consumption are 50 g/day for adults and 20 g/day in children, respectively [Ur-Rehman et al., 2015]; 50 g of xylitol are also safe in infusion solutions for parenteral nutrition [Schneider et al., 2014].

Xylitol belongs to the group of sugar alcohols, polyols, in which the carbonyl moiety (- – - C = O) of carbohydrates is replaced by an alcohol radical (- – - CH-OH). For this reason, most names of sugar alcohols end with “ol” [Nadimi et al., 2011]. Substitution of the carbonyl group with an alcohol group hinders digestion and metabolism, which contributes to the low-glycemic and insulinemic properties [Livesey, 2003]. The increased carbon number of the backbone structure is inversely related to the absorption rate in the intestine. Absorbed xylitol is converted to glycogen or glucose, which is slowly released to the bloodstream. Thus, xylitol demonstrated low-glycemic as well as low-insulinemic indices [Livesey, 2003]. These qualities of xylitol are highly desirable for maintaining stable glucose levels in diabetic subjects [Livesey, 2003].

Also, gastric emptying was significantly slower with xylitol intake as shown in a recent double-blind, cross-over, randomized trial among 5 lean and 5 obese humans [Wölnerhanssen et al., 2016]. This can prevent hunger sensation and food intake. However, low-insulinemic effects were only slightly affected [Wölnerhanssen et al., 2016]. Interestingly, in lean subjects, xylitol intake did not affect glucose excursion, but in obese individuals, it significantly increased plasma glucose response (AUC0–180min) suggesting that obesity is the effect modifier [Wölnerhanssen et al., 2016].

The hallmark of low-glycemic foods is low postprandial glucose excursion, which prevents the subsequent severe hypoglycemic trough [Zhang et al., 2012]. Some more important factors in determining postprandial glycemic response include the fiber contents, ripeness of fruits, fat contents, and the degree of pulverization (in whole grains) [Janket et al., 2008]. In general, low-glycemic foods require extensive mastication due to high fiber content. Thus, dental health directly affects healthy glycemic control aside from a standpoint of inflammation of oral infections [Janket et al., 2008]. With low-glycemic response and slow gastric emptying [Livesey, 2001], xylitol helps in both preventing obesity and maintaining a steady glucose level, an ideal condition for diabetic patients [Nguyen et al., 1993; Natah et al., 1997].

However, recent animal studies conflict with these human studies [Natah et al., 1997; Reyna et al., 2003]. In mice, artificial sweeteners reportedly caused impaired glucose responses [Swithers et al., 2013; Suez et al., 2014]. High-sugar/high-fat diets given to the mice simultaneously in these studies might have biased the results. Weight gain alters the microbiome as previously reported [Janket et al., 2015, 2018]. Although a prominent medical website also has warned readers of the hyperglycemic effects of sugar alcohol consumption [Mayo, 2016], this claim was proven to be a misinterpretation of the original reference [American Diabetes, 2016]. Furthermore, the results from human randomized trials did not support the thesis that artificial sweeteners produce hyperglycemic responses [Grotz et al., 2003; Barriocanal et al., 2008; Maki et al., 2008]. Only when a low-calorie experimental diet was given with sucralose, were significant low-glycemic effects observed [Reyna et al., 2003]. Thus, diet and body weight are strong confounders in the glycemic responses from artificial sweeteners [Reyna et al., 2003; Janket et al., 2015]. The glycemic benefits of artificial sweeteners are likely via the replacement of fermentable car-bohydrates rather than any direct effects [Gardner et al., 2012]. The controversies regarding the role of artificial sweeteners on weight and glycemic control will not subside until large-scale randomized trials in humans with controlled physical activities and diets can be conducted.

The potential untoward consequences associated with the xylitol consumption must also be mentioned. Unabsorbed xylitol can be fermented in the colon by bacteria, resulting in the production of a considerable amount of hydrogen. Some researchers speculate that hydrogen from fermented carbohydrates may alleviate autoimmune colitis by neutralizing oxidative stress [Zhang et al., 2012]. Also, unabsorbed and subsequently fermented xylitol may contribute to the generation of butyric acid that helps in maintaining healthy colonic mucosa [Mäkeläi-nen et al., 2007]. However, the hydrogen gas can also cause flatulence [Sels et al., 1998; Mäkeläinen et al., 2007], and unabsorbed xylitol in the gut can also increase osmotic pressure and cause laxation and diarrhea [Mäkinen, 1984; Storey et al., 2007; Mäkinen, 2016; ]. Additionally, the fecal microbiome was reported to shift from gram-negative to gram-positive bacteria with xylitol consumption [Salminen et al., 1985]. Therefore, utilization of xylitol for its low-glycemic/insulinemic benefits requires careful consideration [Livesey, 2001]. Intestinal dysbiosis associated with xylitol consumption will be discussed further in the next section.

Xylitol Intake and Gut Dysbiosis

The human gut has approximately 100 trillion microbes encompassing 35,000 bacterial species called “gut microbiome” [Frank et al., 2007]. Specific anatomical niches have unique microbiomes [Lloyd-Price et al., 2016], and they are cohabiting and co-evolving with humans. The 4 predominant groups of the gut microbiome are Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria followed byarchaea, viruses, and fungi. A healthy gut contains Firmicutes (32.4–36.5%) and Bacteroidetes (42.0–46.3%). These proportions change in obesity toFirmicutes 48.1% and Bacteroidetes 31.3% [Koliada et al., 2017].

Unlike the gut, the oral cavity is dominated by Firmicutes (41%) and Proteobacteria(20.1%) followed by Bacteroidetes (13%) and Actinobacteria (11.3%) [Dewhirst et al., 2010]. Well-known oral Firmicutes include staphylococci and streptococci, while oral proteobacteria are comprised of gram-negative phyla that include Pseudomonadaceae, Neisseria, Campylobacter, and Helicobacter genera [Dewhirst et al., 2010]. Meanwhile, predominantgutproteobacteriainclude Brucella, Rickettsia as well as Escherichia, Shigella, Salmonella, and Helicobacter. Lastly, oral Bacteroidetes are comprised of the genera Prevotella, Bacteroides, Porphyromonas, Tannerella, Bergeyella, Capnocytophaga, and Actinobacteria[Dewhirst et al., 2010]. Some oral Bacteroidetes are implicated in periodontitis [Mombelli et al., 2000].

What one eats has profound impacts on the oral and gut microbiome and general health [Cani et al., 2008]. Another example of diet influencing the microbiome can be found in the study by De Filippo et al. [2010] where Prevotella and Xylanibacter are enriched in children eating high-fiber diets in Burkina Faso (Fig. 2). These bacteria are minimally present in European children consuming a high-sugar/high-fat Western diet. These facts suggest that a high-fiber African diet may encourage Bacteroidetes growth while the Western diets enrich the growth of Firmicutes [De Filippo et al., 2010]. The microbial composition changes due to different dietsare shown in Figure 2.

Fig. 2.

Different gut microbiota proportions (%) according to dietary patterns.

Fig. 2.

Different gut microbiota proportions (%) according to dietary patterns.

Close modal

It is plausible for the microbiome to change with artificial sweeteners like xylitol which inhibits the growth of predominantly glucose fermenting microbiotas via glucosyltransferase. Indeed, the fecal microbiome shifted from gram-negative to gram-positive bacteria in humans and mice after xylitol consumption [Salminen et al., 1985]. It can be postulated that Firmicutesincluding streptococci die off in the gut and be excreted in feces.

Also, several animal studies reported dysbiosis with artificial sweetener consumption resulting in subsequent impaired glucose metabolism and weight gain [Suez et al., 2014; Burke and Small, 2015]. More specifically, moderate doses of xylitol consumption added to high-fat diets in mice resulted in decreased Bacteroidetes proportion, notably the genus Barnesiella in the family of Porphyromonadaceae while increasing the Firmicutes proportion [Uebanso et al., 2017]. These changes are consistent with the observation in obesity, where the Firmicutes/Bacteroidetes ratio was increased. However, upon examining this study carefully, xylitol in the control diet did not change the weight of the mice. Thus, these dysbiotic changes may be attributable to the high-fat diet [Uebanso et al., 2017].

Gut dysbiosis has been widely believed to cause the metabolic syndrome and other obesity-related comorbidities, but studies that put forth this hypothesis have failed to apply all the causality establishment criteria [Janket et al., 2018]. In a murine model, mice fed Splenda (sucralose and maltodextrin) increased proteobacteria, dysbiosis, and myeloperoxidase reactivity [Rodriguez-Palacios et al., 2018]. However, the increase in proteobacteria could be filling the voids generated by decreased Firmicutes (i.e., streptococci). Indeed, one expert stated that erroneous conclusions can be drawn in identifying one specific microbiota from the microbiome [Cani, 2018]. In vitro human fecal culture with xylitol has increased Anaerostipes hadrus or A. caccae, butyrate producers[Sato et al., 2017]. However, fecal culture is totally different from human trials where many foods and microbiotas are present simultaneously. It is nearly impossible to find one or several microbes causative to the human condition [Foster et al., 2017; Geva-Zatorsky et al., 2017]. Clearly, diet alters the gut microbiome. Therefore, unless the diet is identical in these studies, artificial sweeteners cannot be held culpable for gut dysbiosis. Further research is needed to elucidate how the microbiome changes with the intake of xylitol while holding the diet strictly the same between the compared groups.

Despite the low-glycemic and insulinemic effects of xylitol intake [Natah et al., 1997], several studies reported increased oxaluria, calciuria, and phosphaturia, which are risk factors for urolithiasis [Nguyen et al., 1993; Rodgers et al., 2009]. Researchers speculated that ketohexokinase and aldolase might be involved in oxalic acid formation [Rodgers et al., 2009]. The cause for the oxaluria, calciuria, and phosphaturia from xylitol consumption could be attributable to osmotic diarrhea which may cause metabolic acidosis [Narchi, 1998]. In acidosis, calcium reabsorption decreases leading to calciuria [Lemann et al., 1967]. However, any reference that shows xylitol consumption actually leads to urolithiasis in humans cannot be found.

On a positive note, anin vitro study has proven that xylitol suppressed the growth of α-hemolytic, β-hemolytic streptococci, and S. pneumoniae [Kontiokari et al., 1995]. Assuming the same is true in vivo, xylitol use in cold medications would be beneficial in this regard [Janket, 2012]. Unfortunately, more detrimental results of consumption of xylitol or other artificial sweeteners are mounting. In murine models, Streptococcaceae Streptococcus, Dehalo-bacterium, Anaerostipes, and Ruminococcus were reduced in sucralose-treated mice as expected from glucosyltransferase inhibition [Bian et al., 2017]. These bacteria were inversely associated with colonic inflammation [Willing et al., 2010; Munyaka et al., 2016]. However, upon careful inspection of the reference, it became evident that the gut inflammation caused dysbiosis [Willing et al., 2010; Munyaka et al., 2016], not the artificial sweetener. The sequence of biologic phenomena is important in establishing causality. In the study by Munyaka et al. [2016], gut inflammation was developed by colitis which was induced by dextran sulfate sodium, and colitis resulted in dysbiosis [Janket et al., 2018].

Lastly, some caveats must be stated regarding blind trust in microbiome sequencing data. Due to the variety of factors, this hugely popular concept of gut microbiome research has several flaws. Some studies revealed that microbiome alteration due to diet is largely dependent on genetics [O’Connor et al., 2014] and the analysis technique [Hugon et al., 2013]. Thus, the true diversity of the human gut microbiome remains unknown, and using fecal analyses to estimate the gut microbiome can be a major source of bias in understanding the causal role of the microbiome in human health [Janket et al., 2018].

In conclusion, xylitol has anticaries action when it replaces sugar. Also, low-glycemic and insulinemic effects of xylitol may be beneficial in maintaining a steady glucose level in both diabetic and nondiabetic populations. Whether our attempt to reduce dental caries by suppressing S. mutans will inadvertently cause dysbiosis must be elucidated in future research. Additionally, adverse systemic effects of xylitol require careful further scrutiny. Systemic effects of xylitol intake are summarized in Table 1.

Table 1.

Systemic effects of xylitol intake

Systemic effects of xylitol intake
Systemic effects of xylitol intake

The authors declare no conflicts of interest.

Dr. Janket and Dr. Meurman are the principal investigators; they designed the investigation, participated in the analyses, drafted and finalized the manuscript.

Dr. Ackerson, Dr. Benwait, and Paul Isaac participated in drafting the article and revising it critically for the content. 

All authors gave approval for the final submitted version. 

1.
Almståhl
A
,
Lingström
P
,
Eliasson
L
,
Carlén
A
.
Fermentation of sugars and sugar alcohols by plaque Lactobacillus strains
.
Clin Oral Investig
.
2013
Jul
;
17
(
6
):
1465
70
.
[PubMed]
1432-6981
3.
Bader
JD
,
Vollmer
WM
,
Shugars
DA
,
Gilbert
GH
,
Amaechi
BT
,
Brown
JP
, et al
Results from the Xylitol for Adult Caries Trial (X-ACT)
.
J Am Dent Assoc
.
2013
Jan
;
144
(
1
):
21
30
.
[PubMed]
0002-8177
4.
Barriocanal
LA
,
Palacios
M
,
Benitez
G
,
Benitez
S
,
Jimenez
JT
,
Jimenez
N
, et al
Apparent lack of pharmacological effect of steviol glycosides used as sweeteners in humans. A pilot study of repeated exposures in some normotensive and hypotensive individuals and in Type 1 and Type 2 diabetics
.
Regul Toxicol Pharmacol
.
2008
Jun
;
51
(
1
):
37
41
.
[PubMed]
0273-2300
5.
Beighton
D
.
The complex oral microflora of high-risk individuals and groups and its role in the caries process
.
Community Dent Oral Epidemiol
.
2005
Aug
;
33
(
4
):
248
55
.
[PubMed]
0301-5661
6.
Bian
X
,
Chi
L
,
Gao
B
,
Tu
P
,
Ru
H
,
Lu
K
.
Gut Microbiome Response to Sucralose and Its Potential Role in Inducing Liver Inflammation in Mice
.
Front Physiol
.
2017
Jul
;
8
:
487
.
[PubMed]
1664-042X
7.
Bowen
WH
:
Xylitol for adult caries.
Journal of the American Dental Association (1939)
2013
;144:470.
8.
Bowen
WH
,
Koo
H
.
Biology of Streptococcus mutans-derived glucosyltransferases: role in extracellular matrix formation of cariogenic biofilms
.
Caries Res
.
2011
;
45
(
1
):
69
86
.
[PubMed]
0008-6568
9.
Bowen
WH
,
Pearson
SK
.
The effects of sucralose, xylitol, and sorbitol on remineralization of caries lesions in rats
.
J Dent Res
.
1992
May
;
71
(
5
):
1166
8
.
[PubMed]
0022-0345
10.
Bradshaw
DJ
,
Marsh
PD
.
Effect of sugar alcohols on the composition and metabolism of a mixed culture of oral bacteria grown in a chemostat
.
Caries Res
.
1994
;
28
(
4
):
251
6
.
[PubMed]
0008-6568
11.
Brailsford
SR
,
Tregaskis
RB
,
Leftwich
HS
,
Beighton
D
.
The predominant Actinomyces spp. isolated from infected dentin of active root caries lesions
.
J Dent Res
.
1999
Sep
;
78
(
9
):
1525
34
.
[PubMed]
0022-0345
12.
Burke
MV
,
Small
DM
.
Physiological mechanisms by which non-nutritive sweeteners may impact body weight and metabolism
.
Physiol Behav
.
2015
Dec
;
152
Pt B
:
381
8
.
[PubMed]
0031-9384
13.
Cani
PD
.
Human gut microbiome: hopes, threats and promises
.
Gut
.
2018
Sep
;
67
(
9
):
1716
25
.
[PubMed]
0017-5749
14.
Cani
PD
,
Bibiloni
R
,
Knauf
C
,
Waget
A
,
Neyrinck
AM
,
Delzenne
NM
, et al
Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice
.
Diabetes
.
2008
Jun
;
57
(
6
):
1470
81
.
[PubMed]
0012-1797
15.
Cardoso
CA
,
de Castilho
AR
,
Salomão
PM
,
Costa
EN
,
Magalhães
AC
,
Buzalaf
MA
.
Effect of xylitol varnishes on remineralization of artificial enamel caries lesions in vitro
.
J Dent
.
2014
Nov
;
42
(
11
):
1495
501
.
[PubMed]
0300-5712
16.
Caufield
PW
,
Cutter
GR
,
Dasanayake
AP
.
Initial acquisition of mutans streptococci by infants: evidence for a discrete window of infectivity
.
J Dent Res
.
1993
Jan
;
72
(
1
):
37
45
.
[PubMed]
0022-0345
17.
Caufield
PW
,
Li
Y
,
Dasanayake
A
,
Saxena
D
.
Diversity of lactobacilli in the oral cavities of young women with dental caries
.
Caries Res
.
2007
;
41
(
1
):
2
8
.
[PubMed]
0008-6568
18.
Chi
DL
,
Tut
O
,
Milgrom
P
.
Cluster-randomized xylitol toothpaste trial for early childhood caries prevention
.
J Dent Child (Chic)
.
2014
Jan-Apr
;
81
(
1
):
27
32
.
[PubMed]
1935-5068
19.
Cocco
F
,
Carta
G
,
Cagetti
MG
,
Strohmenger
L
,
Lingström
P
,
Campus
G
.
The caries preventive effect of 1-year use of low-dose xylitol chewing gum. A randomized placebo-controlled clinical trial in high-caries-risk adults
.
Clin Oral Investig
.
2017
Dec
;
21
(
9
):
2733
40
.
[PubMed]
1432-6981
20.
David
LA
,
Maurice
CF
,
Carmody
RN
,
Gootenberg
DB
,
Button
JE
,
Wolfe
BE
, et al
Diet rapidly and reproducibly alters the human gut microbiome
.
Nature
.
2014
Jan
;
505
(
7484
):
559
63
.
[PubMed]
0028-0836
21.
De Filippo
C
,
Cavalieri
D
,
Di Paola
M
,
Ramazzotti
M
,
Poullet
JB
,
Massart
S
, et al
Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa
.
Proc Natl Acad Sci USA
.
2010
Aug
;
107
(
33
):
14691
6
.
[PubMed]
0027-8424
22.
de Paola
PF
,
Alman
J
.
Assessment of the reliability of radiographic diagnosis in a clinical caries trial
.
J Dent Res
.
1972
Sep-Oct
;
51
(
5
):
1431
7
.
[PubMed]
0022-0345
23.
DePaola
PF
,
Soparkar
PM
,
Tavares
M
,
Kent
RL
 Jr
.
Clinical profiles of individuals with and without root surface caries
.
Gerodontology
.
1989
;
8
(
1
):
9
15
.
[PubMed]
0734-0664
24.
Deshpande
A
,
Jadad
AR
.
The impact of polyol-containing chewing gums on dental caries: a systematic review of original randomized controlled trials and observational studies
.
J Am Dent Assoc
.
2008
Dec
;
139
(
12
):
1602
14
.
[PubMed]
0002-8177
25.
Devulapalle
KS
,
Mooser
G
.
Glucosyltransferase inactivation reduces dental caries
.
J Dent Res
.
2001
Feb
;
80
(
2
):
466
9
.
[PubMed]
0022-0345
26.
Dewhirst
FE
,
Chen
T
,
Izard
J
,
Paster
BJ
,
Tanner
AC
,
Yu
WH
, et al
The human oral microbiome
.
J Bacteriol
.
2010
Oct
;
192
(
19
):
5002
17
.
[PubMed]
0021-9193
27.
Dowd
FJ
.
Saliva and dental caries
.
Dent Clin North Am
.
1999
Oct
;
43
(
4
):
579
97
.
[PubMed]
0011-8532
28.
Falony
G
,
Honkala
S
,
Runnel
R
,
Olak
J
,
Nõmmela
R
,
Russak
S
, et al
Long-Term Effect of Erythritol on Dental Caries Development during Childhood: A Posttreatment Survival Analysis
.
Caries Res
.
2016
;
50
(
6
):
579
88
.
[PubMed]
0008-6568
29.
Fontana
M
,
González-Cabezas
C
.
Are we ready for definitive clinical guidelines on xylitol/polyol use?
Adv Dent Res
.
2012
Sep
;
24
(
2
):
123
8
.
[PubMed]
0895-9374
30.
Foster
KR
,
Schluter
J
,
Coyte
KZ
,
Rakoff-Nahoum
S
.
The evolution of the host microbiome as an ecosystem on a leash
.
Nature
.
2017
Aug
;
548
(
7665
):
43
51
.
[PubMed]
0028-0836
31.
Frank
DN
,
St Amand
AL
,
Feldman
RA
,
Boedeker
EC
,
Harpaz
N
,
Pace
NR
.
Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases
.
Proc Natl Acad Sci USA
.
2007
Aug
;
104
(
34
):
13780
5
.
[PubMed]
0027-8424
32.
Gardner
C
,
Wylie-Rosett
J
,
Gidding
SS
,
Steffen
LM
,
Johnson
RK
,
Reader
D
, et al;
American Heart Association Nutrition Committee of the Council on Nutrition, Physical Activity and Metabolism, Council on Arteriosclerosis, Thrombosis and Vascular Biology, Council on Cardiovascular Disease in the Young
;
American Diabetes Association
.
Nonnutritive sweeteners: current use and health perspectives: a scientific statement from the American Heart Association and the American Diabetes Association
.
Diabetes Care
.
2012
Aug
;
35
(
8
):
1798
808
.
[PubMed]
0149-5992
33.
Geva-Zatorsky
N
,
Sefik
E
,
Kua
L
,
Pasman
L
,
Tan
TG
,
Ortiz-Lopez
A
, et al
Mining the Human Gut Microbiota for Immunomodulatory Organisms
.
Cell
.
2017
Feb
;
168
(
5
):
928
943.e11
.
[PubMed]
0092-8674
34.
Giertsen
E
,
Emberland
H
,
Scheie
AA
.
Effects of mouth rinses with xylitol and fluoride on dental plaque and saliva
.
Caries Res
.
1999
;
33
(
1
):
23
31
.
[PubMed]
0008-6568
35.
Grotz
VL
,
Henry
RR
,
McGill
JB
,
Prince
MJ
,
Shamoon
H
,
Trout
JR
, et al
Lack of effect of sucralose on glucose homeostasis in subjects with type 2 diabetes
.
J Am Diet Assoc
.
2003
Dec
;
103
(
12
):
1607
12
.
[PubMed]
0002-8223
36.
Hanno
AG
,
Alamoudi
NM
,
Almushayt
AS
,
Masoud
MI
,
Sabbagh
HJ
,
Farsi
NM
.
Effect of xylitol on dental caries and salivary Streptococcus mutans levels among a group of mother-child pairs
.
J Clin Pediatr Dent
.
2011
;
36
(
1
):
25
30
.
[PubMed]
1053-4628
37.
Hugon
P
,
Lagier
JC
,
Robert
C
,
Lepolard
C
,
Papazian
L
,
Musso
D
, et al
Molecular studies neglect apparently gram-negative populations in the human gut microbiota
.
J Clin Microbiol
.
2013
Oct
;
51
(
10
):
3286
93
.
[PubMed]
0095-1137
38.
Imfeld
T
.
Efficacy of sweeteners and sugar substitutes in caries prevention
.
Caries Res
.
1993
;
27
Suppl 1
:
50
5
.
[PubMed]
0008-6568
39.
Isokangas
P
,
Söderling
E
,
Pienihäkkinen
K
,
Alanen
P
.
Occurrence of dental decay in children after maternal consumption of xylitol chewing gum, a follow-up from 0 to 5 years of age
.
J Dent Res
.
2000
Nov
;
79
(
11
):
1885
9
.
[PubMed]
0022-0345
40.
Janket
S
,
Nunn
ME
,
Salih
E
,
Baird
AE
. Evidence-based approach in transaltional dental research. In:
Meurman
JH
, editor
.
Translational Oral Health Research
.
Berlin, Germany
:
Springer
;
2018
.
41.
Janket
SJ
,
Javaheri
H
,
Ackerson
LK
,
Ayilavarapu
S
,
Meurman
JH
.
Oral Infections, Metabolic Inflammation, Genetics, and Cardiometabolic Diseases
.
J Dent Res
.
2015
Sep
;
94
(
9
Suppl
):
119S
27S
.
[PubMed]
0022-0345
42.
Janket
SJ
. Sugar-free sweeteners; in: Pediatrics for Parents. Gloucester, MA, Sagall, R. MD,
2012
, vol 28.
43.
Janket
SJ
,
Jones
JA
,
Meurman
JH
,
Baird
AE
,
Van Dyke
TE
.
Oral infection, hyperglycemia, and endothelial dysfunction
.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod
.
2008
Feb
;
105
(
2
):
173
9
.
[PubMed]
1079-2104
44.
Koliada
A
,
Syzenko
G
,
Moseiko
V
,
Budovska
L
,
Puchkov
K
,
Perederiy
V
, et al
Association between body mass index and Firmicutes/Bacteroidetes ratio in an adult Ukrainian population
.
BMC Microbiol
.
2017
May
;
17
(
1
):
120
.
[PubMed]
1471-2180
45.
Kontiokari
T
,
Uhari
M
,
Koskela
M
.
Effect of xylitol on growth of nasopharyngeal bacteria in vitro
.
Antimicrob Agents Chemother
.
1995
Aug
;
39
(
8
):
1820
3
.
[PubMed]
0066-4804
46.
Lee
W
,
Spiekerman
C
,
Heima
M
,
Eggertsson
H
,
Ferretti
G
,
Milgrom
P
, et al
The effectiveness of xylitol in a school-based cluster-randomized clinical trial
.
Caries Res
.
2015
;
49
(
1
):
41
9
.
[PubMed]
0008-6568
47.
Lemann
J
 Jr
,
Litzow
JR
,
Lennon
EJ
.
Studies of the mechanism by which chronic metabolic acidosis augments urinary calcium excretion in man
.
J Clin Invest
.
1967
Aug
;
46
(
8
):
1318
28
.
[PubMed]
0021-9738
48.
Lenkkeri
AM
,
Pienihäkkinen
K
,
Hurme
S
,
Alanen
P
.
The caries-preventive effect of xylitol/maltitol and erythritol/maltitol lozenges: results of a double-blinded, cluster-randomized clinical trial in an area of natural fluoridation
.
Int J Paediatr Dent
.
2012
May
;
22
(
3
):
180
90
.
[PubMed]
0960-7439
49.
Livesey
G
.
Tolerance of low-digestible carbohydrates: a general view
.
Br J Nutr
.
2001
Mar
;
85
(
S1
Suppl 1
):
S7
16
.
[PubMed]
0007-1145
50.
Livesey
G
.
Health potential of polyols as sugar replacers, with emphasis on low glycaemic properties
.
Nutr Res Rev
.
2003
Dec
;
16
(
2
):
163
91
.
[PubMed]
0954-4224
51.
Lloyd-Price
J
,
Abu-Ali
G
,
Huttenhower
C
.
The healthy human microbiome
.
Genome Med
.
2016
Apr
;
8
(
1
):
51
.
[PubMed]
1756-994X
52.
Maguire
A
,
Rugg-Gunn
AJ
.
Xylitol and caries prevention—is it a magic bullet?
Br Dent J
.
2003
Apr
;
194
(
8
):
429
36
.
[PubMed]
0007-0610
53.
Mäkeläinen
HS
,
Mäkivuokko
HA
,
Salminen
SJ
,
Rautonen
NE
,
Ouwehand
AC
.
The effects of polydextrose and xylitol on microbial community and activity in a 4-stage colon simulator
.
J Food Sci
.
2007
Jun
;
72
(
5
):
M153
9
.
[PubMed]
0022-1147
54.
Maki KC, Curry LL, Reeves MS, Toth PD, McKenney JM, Farmer MV, et al. Chronic consumption of rebaudioside A, a steviol glycoside, in men and women with type 2 diabetes mellitus. Food Chem Toxicol. 2008;46 Suppl 7:S47–53.
55.
Mäkinen KK. Effect of long-term, peroral administration of sugar alcohols on man. Swed Dent J. 1984;8(3):113–24.
56.
Mäkinen KK. Gastrointestinal Disturbances Associated with the Consumption of Sugar Alcohols with Special Consideration of Xylitol: Scientific Review and Instructions for Dentists and Other Health-Care Professionals. Int J Dent. 2016;2016:5967907.
57.
Mäkinen
KK
,
Bennett
CA
,
Hujoel
PP
,
Isokangas
PJ
,
Isotupa
KP
,
Pape
HR
 Jr
, et al
Xylitol chewing gums and caries rates: a 40-month cohort study
.
J Dent Res
.
1995
Dec
;
74
(
12
):
1904
13
.
[PubMed]
0022-0345
58.
Mäkinen
KK
,
Hujoel
PP
,
Bennett
CA
,
Isotupa
KP
,
Mäkinen
PL
,
Allen
P
.
Polyol chewing gums and caries rates in primary dentition: a 24-month cohort study
.
Caries Res
.
1996
a;
30
(
6
):
408
17
.
[PubMed]
0008-6568
59.
Mäkinen
KK
,
Isotupa
KP
,
Mäkinen
PL
,
Söderling
E
,
Song
KB
,
Nam
SH
, et al
Six-month polyol chewing-gum programme in kindergarten-age children: a feasibility study focusing on mutans streptococci and dental plaque
.
Int Dent J
.
2005
Apr
;
55
(
2
):
81
8
.
[PubMed]
0020-6539
60.
Mäkinen
KK
,
Mäkinen
PL
,
Pape
HR
 Jr
,
Peldyak
J
,
Hujoel
P
,
Isotupa
KP
, et al
Conclusion and review of the Michigan Xylitol Programme (1986-1995) for the prevention of dental caries
.
Int Dent J
.
1996
b
Feb
;
46
(
1
):
22
34
.
[PubMed]
0020-6539
61.
Marsh PD, Percival RS, Challacombe SJ. The influence of denture-wearing and age on the oral microflora. J Dent Res. 1992 Jul;71(7):1374–81.
62.
Mayo
C
. Artificial sweeteners: Any effect on blood sugar? - Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/diabetes/expert-answers/artificial-sweeteners/faq-20058038,
2016
.
63.
Mohan
A
,
Morse
DE
,
O’Sullivan
DM
,
Tinanoff
N
.
The relationship between bottle usage/content, age, and number of teeth with mutans streptococci colonization in 6-24-month-old children
.
Community Dent Oral Epidemiol
.
1998
Feb
;
26
(
1
):
12
20
.
[PubMed]
0301-5661
64.
Mombelli
A
,
Schmid
B
,
Rutar
A
,
Lang
NP
.
Persistence patterns of Porphyromonas gingivalis, Prevotella intermedia/nigrescens, and Actinobacillus actinomyetemcomitans after mechanical therapy of periodontal disease
.
J Periodontol
.
2000
Jan
;
71
(
1
):
14
21
.
[PubMed]
0022-3492
65.
Munyaka
PM
,
Rabbi
MF
,
Khafipour
E
,
Ghia
JE
.
Acute dextran sulfate sodium (DSS)-induced colitis promotes gut microbial dysbiosis in mice
.
J Basic Microbiol
.
2016
Sep
;
56
(
9
):
986
98
.
[PubMed]
0233-111X
66.
Nadimi
H
,
Wesamaa
H
,
Janket
SJ
,
Bollu
P
,
Meurman
JH
.
Are sugar-free confections really beneficial for dental health?
Br Dent J
.
2011
Oct
;
211
(
7
):
E15
.
[PubMed]
0007-0610
67.
Narchi
H
.
Serum bicarbonate and dehydration severity in gastroenteritis
.
Arch Dis Child
.
1998
Jan
;
78
(
1
):
70
1
.
[PubMed]
0003-9888
68.
Natah
SS
,
Hussien
KR
,
Tuominen
JA
,
Koivisto
VA
.
Metabolic response to lactitol and xylitol in healthy men
.
Am J Clin Nutr
.
1997
Apr
;
65
(
4
):
947
50
.
[PubMed]
0002-9165
69.
Nguyen
MS
,
Saag
M
,
Voog-Oras
Ü
,
Nguyen
T
,
Jagomägi
T
.
Temporomandibular Disorder Signs, Occlusal Support, and Craniofacial Structure Changes Among the Elderly Vietnamese
.
J Maxillofac Oral Surg
.
2018
Sep
;
17
(
3
):
362
71
.
[PubMed]
0972-8279
70.
Nguyen
NU
,
Dumoulin
G
,
Henriet
MT
,
Berthelay
S
,
Regnard
J
.
Carbohydrate metabolism and urinary excretion of calcium and oxalate after ingestion of polyol sweeteners
.
J Clin Endocrinol Metab
.
1993
Aug
;
77
(
2
):
388
92
.
[PubMed]
0021-972X
71.
O'Connor
A
,
Quizon
PM
,
Albright
JE
,
Lin
FT
,
Bennett
BJ
:
Responsiveness of cardiometabolic-related microbiota to diet is influenced by host genetics.
Mammalian genome : official journal of the International Mammalian Genome Society
2014
;25:583-599.
72.
Reyna
NY
,
Cano
C
,
Bermúdez
VJ
,
Medina
MT
,
Souki
AJ
,
Ambard
M
, et al
Sweeteners and beta-glucans improve metabolic and anthropometrics variables in well controlled type 2 diabetic patients
.
Am J Ther
.
2003
Nov-Dec
;
10
(
6
):
438
43
.
[PubMed]
1075-2765
73.
Ribeiro
AA
,
Azcarate-Peril
MA
,
Cadenas
MB
,
Butz
N
,
Paster
BJ
,
Chen
T
, et al
The oral bacterial microbiome of occlusal surfaces in children and its association with diet and caries
.
PLoS One
.
2017
Jul
;
12
(
7
):
e0180621
.
[PubMed]
1932-6203
74.
Roberts
MC
,
Riedy
CA
,
Coldwell
SE
,
Nagahama
S
,
Judge
K
,
Lam
M
, et al
How xylitol-containing products affect cariogenic bacteria
.
J Am Dent Assoc
.
2002
Apr
;
133
(
4
):
435
41
.
[PubMed]
0002-8177
75.
Rodgers
A
,
Bungane
N
,
Allie-Hamdulay
S
,
Lewandowski
S
,
Webber
D
.
Calciuria, oxaluria and phosphaturia after ingestion of glucose, xylitol and sorbitol in two population groups with different stone-risk profiles
.
Urol Res
.
2009
Jun
;
37
(
3
):
121
5
.
[PubMed]
0300-5623
76.
Rodriguez-Palacios
A
,
Harding
A
,
Menghini
P
,
Himmelman
C
,
Retuerto
M
,
Nickerson
KP
, et al
The Artificial Sweetener Splenda Promotes Gut Proteobacteria, Dysbiosis, and Myeloperoxidase Reactivity in Crohn’s Disease-Like Ileitis
.
Inflamm Bowel Dis
.
2018
Apr
;
24
(
5
):
1005
20
.
[PubMed]
1078-0998
77.
Rothman
KJ
.
Epidemiologic methods in clinical trials
.
Cancer
.
1977
Apr
;
39
(
4
Suppl
):
1771
5
.
[PubMed]
0008-543X
78.
Salminen
S
,
Salminen
E
,
Koivistoinen
P
,
Bridges
J
,
Marks
V
:
Gut microflora interactions with xylitol in the mouse, rat and man.
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
1985
;23:985-990.
79.
Sansone
C
,
Van Houte
J
,
Joshipura
K
,
Kent
R
,
Margolis
HC
.
The association of mutans streptococci and non-mutans streptococci capable of acidogenesis at a low pH with dental caries on enamel and root surfaces
.
J Dent Res
.
1993
Feb
;
72
(
2
):
508
16
.
[PubMed]
0022-0345
80.
Sato
T
,
Kusuhara
S
,
Yokoi
W
,
Ito
M
,
Miyazaki
K
.
Prebiotic potential of L-sorbose and xylitol in promoting the growth and metabolic activity of specific butyrate-producing bacteria in human fecal culture
.
FEMS Microbiol Ecol
.
2017
Jan
;
93
(
1
):
93
.
[PubMed]
0168-6496
81.
Scheinin
A
,
Mäkinen
KK
,
Tammisalo
E
,
Rekola
M
.
Turku sugar studies XVIII. Incidence of dental caries in relation to 1-year consumption of xylitol chewing gum
.
Acta Odontol Scand
.
1975
;
33
(
5
):
269
78
.
[PubMed]
0001-6357
82.
Schneider AS, Schettler A, Markowski A, Luettig B, Momma M, Seipt C, et al. Assessment of xylitol serum levels during the course of parenteral nutrition including xylitol in intensive care patients: a case control study. Clin Nutr. 2014 Jun;33(3):483–8.
83.
Schroth
RJ
,
Lavelle
C
,
Tate
R
,
Bruce
S
,
Billings
RJ
,
Moffatt
ME
.
Prenatal vitamin D and dental caries in infants
.
Pediatrics
.
2014
May
;
133
(
5
):
e1277
84
.
[PubMed]
0031-4005
84.
Sels
JP
,
Verdonk
HE
,
Wolffenbuttel
BH
.
Effects of acarbose (Glucobay) in persons with type 1 diabetes: a multicentre study
.
Diabetes Res Clin Pract
.
1998
Aug
;
41
(
2
):
139
45
.
[PubMed]
0168-8227
85.
Shen
P
,
Walker
GD
,
Yuan
Y
,
Reynolds
C
,
Reynolds
EC
.
Polyols and remineralisation of enamel subsurface lesions
.
J Dent
.
2017
Nov
;
66
:
71
5
.
[PubMed]
0300-5712
86.
Sintes
JL
,
Elías-Boneta
A
,
Stewart
B
,
Volpe
AR
,
Lovett
J
.
Anticaries efficacy of a sodium monofluorophosphate dentifrice containing xylitol in a dicalcium phosphate dihydrate base. A 30-month caries clinical study in Costa Rica
.
Am J Dent
.
2002
Aug
;
15
(
4
):
215
9
.
[PubMed]
0894-8275
87.
Sintes
JL
,
Escalante
C
,
Stewart
B
,
McCool
JJ
,
Garcia
L
,
Volpe
AR
, et al
Enhanced anticaries efficacy of a 0.243% sodium fluoride/10% xylitol/silica dentifrice: 3-year clinical results
.
Am J Dent
.
1995
Oct
;
8
(
5
):
231
5
.
[PubMed]
0894-8275
88.
Smith
DJ
,
Taubman
MA
,
Ebersole
JL
.
Effect of oral administration of glucosyltransferase antigens on experimental dental caries
.
Infect Immun
.
1979
Oct
;
26
(
1
):
82
9
.
[PubMed]
0019-9567
89.
Söderling
E
,
Isokangas
P
,
Pienihäkkinen
K
,
Tenovuo
J
,
Alanen
P
.
Influence of maternal xylitol consumption on mother-child transmission of mutans streptococci: 6-year follow-up
.
Caries Res
.
2001
May-Jun
;
35
(
3
):
173
7
.
[PubMed]
0008-6568
90.
Splieth
CH
,
Alkilzy
M
,
Schmitt
J
,
Berndt
C
,
Welk
A
:
Effect of xylitol and sorbitol on plaque acidogenesis.
Quintessence international (Berlin, Germany : 1985)
2009
;40:279-285.
91.
Storey
D
,
Lee
A
,
Bornet
F
,
Brouns
F
.
Gastrointestinal tolerance of erythritol and xylitol ingested in a liquid
.
Eur J Clin Nutr
.
2007
Mar
;
61
(
3
):
349
54
.
[PubMed]
0954-3007
92.
Suez
J
,
Korem
T
,
Zeevi
D
,
Zilberman-Schapira
G
,
Thaiss
CA
,
Maza
O
, et al
Artificial sweeteners induce glucose intolerance by altering the gut microbiota
.
Nature
.
2014
Oct
;
514
(
7521
):
181
6
.
[PubMed]
0028-0836
93.
Swithers
SE
,
Sample
CH
,
Davidson
TL
.
Adverse effects of high-intensity sweeteners on energy intake and weight control in male and obesity-prone female rats
.
Behav Neurosci
.
2013
Apr
;
127
(
2
):
262
74
.
[PubMed]
0735-7044
94.
Tabrizi
R
,
Karagah
T
,
Aliabadi
E
,
Hoseini
SA
.
Does gum chewing increase the prevalence of temporomandibular disorders in individuals with gum chewing habits?
J Craniofac Surg
.
2014
Sep
;
25
(
5
):
1818
21
.
[PubMed]
1049-2275
95.
Thabuis
C
,
Cheng
CY
,
Wang
X
,
Pochat
M
,
Han
A
,
Miller
L
,
Wils
D
,
Guerin-Deremaux
L
:
Effects of maltitol and xylitol chewing-gums on parameters involved in dental caries development.
European journal of paediatric dentistry : official journal of European Academy of Paediatric Dentistry
2013
;14:303-308.
96.
Thorild
I
,
Lindau
B
,
Twetman
S
.
Salivary mutans streptococci and dental caries in three-year-old children after maternal exposure to chewing gums containing combinations of xylitol, sorbitol, chlorhexidine, and fluoride
.
Acta Odontol Scand
.
2004
Oct
;
62
(
5
):
245
50
.
[PubMed]
0001-6357
97.
Trahan
L
,
Bareil
M
,
Gauthier
L
,
Vadeboncoeur
C
.
Transport and phosphorylation of xylitol by a fructose phosphotransferase system in Streptococcus mutans
.
Caries Res
.
1985
;
19
(
1
):
53
63
.
[PubMed]
0008-6568
98.
Uebanso
T
,
Kano
S
,
Yoshimoto
A
,
Naito
C
,
Shimohata
T
,
Mawatari
K
, et al
Effects of Consuming Xylitol on Gut Microbiota and Lipid Metabolism in Mice
.
Nutrients
.
2017
Jul
;
9
(
7
):
9
.
[PubMed]
2072-6643
99.
Ur-Rehman
S
,
Mushtaq
Z
,
Zahoor
T
,
Jamil
A
,
Murtaza
MA
.
Xylitol: a review on bioproduction, application, health benefits, and related safety issues
.
Crit Rev Food Sci Nutr
.
2015
;
55
(
11
):
1514
28
.
[PubMed]
1040-8398
100.
Vadeboncoeur
C
,
Trahan
L
,
Mouton
C
,
Mayrand
D
.
Effect of xylitol on the growth and glycolysis of acidogenic oral bacteria
.
J Dent Res
.
1983
Aug
;
62
(
8
):
882
4
.
[PubMed]
0022-0345
101.
Van Loveren
C
.
Sugar alcohols: what is the evidence for caries-preventive and caries-therapeutic effects?
Caries Res
.
2004
May-Jun
;
38
(
3
):
286
93
.
[PubMed]
0008-6568
102.
Vieira
SM
,
Pagovich
OE
,
Kriegel
MA
.
Diet, microbiota and autoimmune diseases
.
Lupus
.
2014
May
;
23
(
6
):
518
26
.
[PubMed]
0961-2033
103.
Watthanasaen
S
,
Merchant
AT
,
Luengpailin
S
,
Chansamak
N
,
Pisek
A
,
Pitiphat
W
.
Xylitol-containing Chewing Gum for Caries Prevention in Students with Disabilities: A Randomised Trial
.
Oral Health Prev Dent
.
2017
;
15
(
6
):
519
27
.
[PubMed]
1602-1622
104.
Wennerholm
K
,
Arends
J
,
Birkhed
D
,
Ruben
J
,
Emilson
CG
,
Dijkman
AG
.
Effect of xylitol and sorbitol in chewing-gums on mutans streptococci, plaque pH and mineral loss of enamel
.
Caries Res
.
1994
;
28
(
1
):
48
54
.
[PubMed]
0008-6568
105.
Wennerholm
K
,
Birkhed
D
,
Emilson
CG
.
Effects of sugar restriction on Streptococcus mutans and Streptococcus sobrinus in saliva and dental plaque
.
Caries Res
.
1995
;
29
(
1
):
54
61
.
[PubMed]
0008-6568
106.
Wennerholm
K
,
Emilson
CG
.
Effect of sorbitol- and xylitol-containing chewing gum on salivary microflora, saliva, and oral sugar clearance
.
Scand J Dent Res
.
1989
Jun
;
97
(
3
):
257
62
.
[PubMed]
0029-845X
107.
Willing
BP
,
Dicksved
J
,
Halfvarson
J
,
Andersson
AF
,
Lucio
M
,
Zheng
Z
,
Jarnerot
G
,
Tysk
C
,
Jansson
JK
,
Engstrand
L
:
A pyrosequencing study in twins shows that gastrointestinal microbial profiles vary with inflammatory bowel disease phenotypes.
Gastroenterology
2010
;139:1844-1854.e1841.
108.
Wölnerhanssen
BK
,
Cajacob
L
,
Keller
N
,
Doody
A
,
Rehfeld
JF
,
Drewe
J
, et al
Gut hormone secretion, gastric emptying, and glycemic responses to erythritol and xylitol in lean and obese subjects
.
Am J Physiol Endocrinol Metab
.
2016
Jun
;
310
(
11
):
E1053
61
.
[PubMed]
0193-1849
109.
Zhan
L
,
Cheng
J
,
Chang
P
,
Ngo
M
,
Denbesten
PK
,
Hoover
CI
, et al
Effects of xylitol wipes on cariogenic bacteria and caries in young children
.
J Dent Res
.
2012
Jul
;
91
(
7
Suppl
):
85S
90S
.
[PubMed]
0022-0345
110.
Zhang
DQ
,
Zhu
JH
,
Chen
WC
.
Acarbose: a new option in the treatment of ulcerative colitis by increasing hydrogen production
.
Afr J Tradit Complement Altern Med
.
2012
Oct
;
10
(
1
):
166
9
.
[PubMed]
0189-6016
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