Enhancing Fluoride: Clinical Human Studies of Alternatives or Boosters for Caries Management

Abstract

Dental caries remains a major public health problem, especially for certain high-risk population groups. The goal of this study was to assess the evidence regarding strategies meant to be used as alternatives or booster/supplements to fluoride for caries prevention and management. Articles were selected for inclusion if they had a prospective longitudinal design, with a fluoride control arm, and were conducted in human subjects. Of the included studies, 7/18 studies on calcium-based strategies favored the test product (the majority of studies included exposure of fluoride in all groups). All the arginine studies (8/8) included a combination of arginine and a calcium base, and concluded that this has the potential to significantly boost the performance of fluoride. The remaining included studies focused on the addition of microbial-related strategies to a fluoride-containing vehicle (2 xylitol studies and 1 study using a probiotic milk), and all favored the combination as a booster to fluoride. Thus, the current study did not identify evidence for any strategy to effectively be used as a substitute or alternative to fluoride, but identified some consistent evidence derived from the use of prebiotic strategies (primarily from use of arginine combined with calcium) to support their potential use to boost the mechanism of action of fluoride. Thus, fluoride-based strategies remain the standard for caries prevention and management, with some evidence that boosting the effects of fluoride by the use of prebiotic strategies is a promising possibility.

State of the Art Enamel Remineralization Systems: The Next Frontier in Caries Management

“…While under normal physiological conditions, fluoride and salivary homeostatic mechanisms are often enough to remineralize early lesions, these are not adequate in highly cariogenic oral environments. Other at-risk population groups (xerostomia patients, elderly individuals at risk of root caries) can also benefit from boosters to improve the remineralizing and preventive efficacy of fluoride [Fontana, 2016].…”

“…However, other RCTs contradict the above studies as they did not report any superior added effect for CPP-ACP [Beerens et al, 2010;Brochner et al, 2011;Huang et al, 2013;Plonka et al, 2013;Singh et al, 2016;Sitthisettapong et al, 2012Sitthisettapong et al, , 2015. Published literature and systematic reviews also reach conflicting conclusions, with some reviews suggesting that CPP-ACP had significant remineralizing and caries preventive effects [Llena et al, 2009;Wang et al, 2017;Yengopal and Mickenautsch, 2009], while others conclude that the evidence to support its long-term remineralizing or synergistic effect with fluoride is limited [Azarpazhooh and Limeback, 2008;Fontana, 2016;Li et al, 2014;Raphael and Blinkhorn, 2015;Zero, 2009].…”

In situ Effect of Arginine-Containing Dentifrice on Plaque Composition and on Enamel Demineralization under Distinct Cariogenic Conditions

“…In an effort to enhance the anticaries effect of fluoride on caries management, several compounds have been added to FD [Fontana, 2016]. Recently, arginine has been incorporated into dentifrice formulations to suppress mineral loss via a buffering effect induced by arginine [Cummins, 2013a].…”

Calcium-Phosphate-Osteopontin Particles Reduce Biofilm Formation and pH Drops in in situ Grown Dental Biofilms

“…Such strategies including prebiotics (arginine, xylitol) and probiotics have shown promising results for caries control, but their clinical efficacy may not surpass that of conventional fluoridebased strategies [for a review, see Fontana, 2016]. Similarly, a large body of work has investigated the caries controlling effect of casein phosphopeptide-stabilized amorphous calcium phosphate (CPP-ACP), albeit with differing results [Li et al, 2014;Fontana, 2016].…”

“…Such strategies including prebiotics (arginine, xylitol) and probiotics have shown promising results for caries control, but their clinical efficacy may not surpass that of conventional fluoridebased strategies [for a review, see Fontana, 2016]. Similarly, a large body of work has investigated the caries controlling effect of casein phosphopeptide-stabilized amorphous calcium phosphate (CPP-ACP), albeit with differing results [Li et al, 2014;Fontana, 2016]. While the main proposed mechanism of CPP-ACP is the provision of calcium and phosphate in solution, which in turn enhances remineralization [Reynolds, 1997], casein, as well as other milk proteins, have been reported to affect bacterial adhesion and retard dental biofilm formation [Guggenheim et al, 1999;Arslan et al, 2009;Danielsson Niemi et al, 2009;Wakabayashi et al, 2009].…”