Polyphosphate-based strategies in enamel remineralization: mechanisms, evidence, and clinical potential

Minimally invasive management of initial enamel caries focuses on strategies that promote subsurface remineralization while limiting fluoride exposure, particularly in children. Phosphate salts such as sodium trimetaphosphate (TMP), sodium hexametaphosphate (SHMP) and calcium glycerophosphate (CaGP) have therefore been incorporated into topical fluoride formulations as interfacial modifiers. This narrative review critically examines mechanisms, experimental evidence and clinical data on polyphosphate systems for early enamel carious lesions. Relevant literature from databases including PubMed, Scopus, Cochrane and ScienceDirect was reviewed, focusing on in vitro, in situ and in vivo human studies including clinical trials evaluating TMP-, SHMP- or CaGP-containing products. Available evidence indicates that these salts adsorb to enamel, assemble ion-rich surface layers, modulate biofilm acidogenicity and favor deeper subsurface repair, with nano-sized forms amplifying these effects. Across toothpastes, gels and varnishes, in vitro and in situ studies suggest that several low-fluoride polyphosphate formulations may achieve mineral uptake comparable to conventional 1,100-ppm F products, when fluoride:polyphosphate ratios were kept within a favorable window. Available clinical trials, although few and heterogeneous, suggest caries reduction in children using low-fluoride toothpastes containing polyphosphate salts. Overall, polyphosphate systems may represent a relevant option for subsurface enamel remineralization in susceptible groups, while longer-term clinical evaluation is still needed.