Despite being easily preventable, dental caries is the most prevalent chronic disease all over the world and is regarded as an important public health problem (Peres et al., 2019). According to a recent systematic review, the global prevalence of dental caries is 46.2% (95% CI: 41.6–50.8%) in primary teeth in children and 53.8% (95% CI: 50–57.5%) in permanent teeth (Kazeminia et al., 2020). Huge sums of money are spent to treat caries and its sequelae. In the European Union, in 2011, annual expenditures with dental treatment were estimated at EUR 79 billion (Rugg-Gunn, 2013), while in the USA this expenditure was US$ 85 billion in 2012 (Hung et al., 2020). According to the World Health Organization (WHO) 2012 reports, around 60–90% of children and nearly 100% of adults have or had caries experience that frequently causes pain or discomfort. In addition, dental diseases including caries are the main cause of absence of children in the schools (Rugg-Gunn, 2013).

Since the classic Turku studies in the 1970 ´s (Scheinin and Makinen, 1971, Scheinin et al., 1976, Scheinin and Makinen, 1976) xylitol has been evaluated as a potential therapeutic agent against caries. Different vehicles, such as solutions, chewing gums, toothpastes, lozenges, wipes and varnishes have been tested using in vitro, in situ and clinical protocols. Among the different xylitol-containing vehicles to control caries, some evidence has been found for toothpastes, despite the quality is low (Riley et al., 2015). Our group has reported promising results with xylitol-containing varnishes for remineralization of enamel lesions in vitro (Cardoso et al., 2014), in situ (Cardoso et al., 2016) and for the remineralization of immature teeth (Siqueira et al., 2021). When these studies are analyzed together, it seems that xylitol might protect against caries, but additional studies employing protocols that more closely resemble the clinical condition must be performed.

One question that arises when we think of xylitol as a potential agent against caries is how does it act? Many studies report a reduction in salivary levels of Streptococcus mutans due to the prolonged and continuous exposure to xylitol by chewing gums, indicating that this polyol can decrease the ability of the bacteria to multiply (Stecksen-Blicks et al., 2004, Thaweboon et al., 2004, Thorild et al., 2004). However, the clinical relevance of reduced intra-oral levels of this microorganism is still unclear (Takahashi and Washio, 2011) as not all studies confirm the inhibitory effect of xylitol on S. mutans (Antonio et al., 2011). Further studies are needed to elucidate the mechanism of the anticaries effects of xylitol considering its impact on the microbiome and bacterial virulence, in addition to cariogenic bacteria levels as well as their benefits for overall health (Zhan, 2018). Moreover, the antibacterial effect of xylitol is not able to explain its effect against erosive tooth wear since these lesions occur on a surface devoid of dental biofilm.

Another probable mechanism of action of xylitol is on enamel remineralization. This polyol has been shown to have the ability to form complexes with calcium ions on the dental surface, inhibiting the translocation of dissolved calcium and phosphate, and the resultant demineralization (Arends et al., 1984, Arends et al., 1990). A study involving high-resolution electron microscopy and microradiography revealed a higher remineralization in intermediate and deep layers of enamel samples immersed in 20% xylitol solution compared with control (Miake et al., 2003). Thus, xylitol could be a possible alternative to remineralize deep caries lesions. However, a more recent study demonstrated that polyols at physiologically relevant concentrations (12.6%) did not promote remineralization of enamel subsurface lesions by facilitating calcium uptake into the lesion (Shen et al., 2017).

Considering the promising effect of xylitol on caries and the lack of studies analyzing its effect and interaction with fluoride (F), the aims of the present study were to evaluate the effect of xylitol and its combined effect with F to: 1) reduce enamel demineralization under a cariogenic challenge and 2) enhance remineralization of shallow and deep enamel lesions in vitro. The tested null hypotheses were: 1) treatment with xylitol combined or not to fluoride does not reduce enamel demineralization under a pH cycling and 2) the same treatments do not enhance remineralization of shallow and deep enamel lesions in vitro.