Objective: This systematic review with meta-analyses sought to answer the following question: "Does CPP-ACP [casein phosphopeptide-amorphous calcium phosphate], when introduced into the oral environment, provide any caries-preventive benefit superior to that of any other intervention or placebo?"
Material and methods: Seven electronic databases were searched for trials relevant to the review question. Twelve articles were accepted after application of inclusion and exclusion criteria.
Results: Of the accepted articles, five in situ randomized control trials (RCT) could be pooled for meta-analyses. During the short-term (7-21 days) in situ trials, participants wore appliances containing enamel slabs that were analyzed in the laboratory after exposure to CPP-ACP. The pooled in situ results showed a weighted mean difference (WMD) of the percentage remineralization scores in favor of chewing gum with 18.8 mg CPP-ACP as compared to chewing gum without CPP-ACP (WMD -8.01; 95% CI: -10.54 to -5.48; p = 0.00001), as well as compared to no intervention (WMD -13.56; 95% CI: -16.49 to -10.62; p = 0.00001). A significant higher remineralization effect was also observed after exposure to 10.0 mg CPP-ACP (-7.75; 95% CI: -9.84 to -5.66; p = 0.00001). One long-term in vivo RCT (24 months) with a large sample size (n = 2720) found that the odds of a tooth surface's progressing to caries was 18% less in subjects who chewed sugar-free gum containing 54 mg CPP-ACP than in control subjects who chewed gum without CPP-ACP (p = 0.03).
Conclusion: Within the limitations of this systematic review with meta-analysis, the results of the clinical in situ trials indicate a short-term remineralization effect of CPP-ACP. Additionally, the promising in vivo RCT results suggest a caries-preventing effect for long-term clinical CPP-ACP use. Further randomized control trials are needed in order to confirm these initial results in vivo.