Review finds limited evidence for effectiveness of Casein phosphopeptide-amorphous calcium phosphate in caries prevention

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Dental caries remains a major public health problem. It has been demonstrated in in vitro studies that Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) has a remineralising effect on enamel lesions. The aim of this systematic review was to assess the long-term (>3 months) remineralizing effect of CPP-ACP on early caries lesions in vivo compared with placebo and/or fluorides.

Searches were conducted in the Medline, Web of Science, Embase, CENTRAL ( Cochrane), Science Direct, CBM (Chinese Biological Medical), CNKI (Chinese National Knowledge Infrastructure), the National Research Register, OpenGrey, and The World Health Organization’s International Clinical Trial Registry Platform databases. Randomized or quasi-randomized clinical trials with a follow- up period of more than 3 months were included. Studies using topical CPP-ACP in any modality, including toothpaste, mouth-rinses, tooth mousse, and chewing gum were included. There were no restrictions regarding the dose, frequency, duration, and method of administration. Two reviewers independently carried out the screening of studies, quality assessment and data abstraction.

  • 8 studies involving 2367 participants were included, (6 randomised controlled trials and 2 controlled trials).
  • Only 1 study was considered to have a low risk of bias, 5 a high risk and 2 unclear risk.
  • Follow up ranged from 3-24 months.
  • 3 studies evaluated the effect of CPP-ACP on caries and 5 assessed the effect on white spot lesions during orthodontic treatment
  • Meta-analysis was impossible both due to high risk of bias and clinical heterogeneity.

The authors concluded

Within the limitation of this systematic review, CPP-ACP was found to have a long-term remineralization effect on early caries lesions in comparison with placebo, although this effect was not significantly different from that of fluoride agents. The clinical benefits of using CPP-ACP supplements over fluoride are still unclear. Well-designed RCTs are, therefore, required to improve the level of evidence in this area.


The reviewers only identified a small number of studies of limited quality to address this question. Also the range of delivery methods, gum, toothpaste, mousse, cream and the range of difference concentrations of CPP-ACP used (2% to 10% w/w) makes comparisons difficult. Three of the included studies were only of 12 weeks duration and despite improvement sin early caries detection this is too short a time period. For example the Cochrane review on fluoride varnish and toothpaste only included studies with a follow up period of one years or more. An earlier review by Yengopal and Mickenautsch (2009) which also considered short-term studies included 12 studies (5 RCTs) suggested a short-term remineralising effect and promising longer term effect. One of the studies included in this latest reviews was considered by the Dental Elf in 2012.


Li J, Xie X, Wang Y, Yin W, Antoun JS, Farella M, Mei L. Long-term remineralizing effect of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) on early caries lesions in vivo: A systematic review. J Dent. 2014 Jul;42(7):769-777. doi: 10.1016/j.jdent.2014.03.015. Epub 2014 Apr 3. Review. PubMed PMID: 24705069.

Yengopal V, Mickenautsch S. Caries preventive effect of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP): a meta-analysis. Acta Odontol Scand. 2009;67(6):321-32. PubMed PMID: 19701818.

Dental Elf 25th July 2012 – In pre-school children addition of casein phosphopeptide-amorphous calcium phosphate paste to regular brushing with fluoridated toothpaste did not have added decay prevention effect


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