Supplementary Material for: Effect of CPP-ACP added to Milk, Chewing Gum and Candy on Dental Caries: a Systematic Review

Casein is one of the most studied proteins with activity against dental caries. In particular, casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) has shown promising remineralizing properties. In vivo evidence on the anticaries potential of CPP-ACP added to foodstuffs is elusive, nonetheless. Hence, this systematic review aimed at determining whether the use of CPP-ACP added to foodstuffs has a remineralizing or inhibitory action on dental demineralization either in vivo or in situ. The review protocol followed the PRISMA-P criteria and was registered in PROSPERO. PubMed, SCOPUS, and Web of Science databases were searched using predefined criteria, based on the PICO question; Is there an effect on dental caries upon adding CPP-ACP to milk, chewing gums, or candies? No year or language limits were applied. Article selection and data extraction were carried out independently by 2 investigators. Two hundred-ten titles were examined, 23 selected for full-text review and 16 studies included (2 in vivo, and 14 in situ). In 2 studies, CPP-ACP was added in candy, in 2 to milk and in 12 to chewing gum. The main outcomes included enamel remineralization and activity against dental biofilm. The overall quality of the evidence was classified as moderate. The available evidence suggests that CPP-ACP added to milk, chewing gum or candy has a potential remineralizing activity on tooth enamel, with some additional antibacterial activity on the dental biofilm. Further clinical studies are needed to verify if this effect is clinically significant in reducing the caries lesion incidence or to revert the demineralizing process.

酪蛋白（Casein）是目前研究最为广泛的抗龋齿活性蛋白之一。其中，酪蛋白磷酸肽-无定形磷酸钙（casein phosphopeptide-amorphous calcium phosphate, CPP-ACP）展现出颇具前景的牙齿再矿化特性。然而，目前关于添加至食品中的CPP-ACP抗龋潜力的体内研究证据仍不甚明确。因此，本系统综述旨在明确添加至食品中的CPP-ACP在体内或口内环境下，对牙齿脱矿是否具有再矿化或抑制作用。本综述方案遵循PRISMA-P标准，并已在PROSPERO平台注册。研究团队基于PICO（人群、干预、对照、结局）框架的预设检索标准，对PubMed、SCOPUS及Web of Science数据库进行了全面检索，所针对的研究问题为：将CPP-ACP添加至牛奶、口香糖或糖果中是否会对龋齿产生影响？本次检索未设置年份及语言限制。由2名研究者独立完成文献筛选及数据提取工作。共计检索到210条标题文献，经筛选后纳入23篇进行全文审阅，最终纳入16项研究（其中2项为体内研究，14项为口内研究）。在纳入的研究中，2项将CPP-ACP添加至糖果中，2项添加至牛奶中，剩余12项添加至口香糖中。本综述的主要结局指标包括牙釉质再矿化效果及抗牙菌斑活性。经评估，本次研究的证据整体质量等级为中等。现有证据表明，添加至牛奶、口香糖或糖果中的CPP-ACP对牙釉质具有潜在的再矿化活性，同时对牙菌斑具备一定的抗菌活性。未来仍需开展更多临床研究，以验证该效应在降低龋齿病变发生率或逆转牙齿脱矿过程中是否具有临床意义。