Long-term remineralizing effect of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) on early caries lesions in vivo: A systematic review

Objective: To assess the long-term (>3 months) remineralizing effect of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) on early caries lesions in vivo. Data sources: PubMed, Web of Science, Embase, Cochrane-Central, Science Direct, CBM, and CNKI were searched up to April 2013. Only articles in English and Chinese were included. Grey literature was also searched. Randomized or quasi-randomized clinical trials in which CPP-ACP was delivered by any method were considered. All relevant studies underwent two independent reviews. Study selection: Of the 738 studies screened, 83 studies were reviewed and eight selected for inclusion in the final sample. The follow-up period of the studies included varied from 3 to 24 months. The long-term remineralizing effect of CPP-ACP in vivo was demonstrated in comparison with placebo in randomized controlled trial. However, there is conflicting evidence regarding the clinical efficacy of CPP-ACP when used in conjunction with fluoride toothpastes. No specific side effect related to CPP-ACP usage was found. Conclusions: CPP-ACP has a long-term remineralizing effect on early caries lesions in comparison with placebo, although this does not appear to be significantly different from that of fluorides. The advantage of using CPP-ACP as a supplement to fluoride-containing products is still unclear. High-quality, well-designed clinical studies in this area are still required before definitive recommendations can be made. Clinical significance: CPP-ACP is a promising remineralizing agent with a significant remineralizing effect that has been demonstrated in both in vivo and in vitro studies. The evidence to support its synergistic effect with fluoride is insufficient based on the current existing long-term human randomized controlled trials.