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Research · Supplements

CPP-ACP

Reviews found CPP-ACP pastes remineralized white spot lesions more than placebo, but not clearly more than fluoride, and adding CPP-ACP to fluoride gave no clinically relevant gain. In 2,720 adolescents, CPP-ACP gum lowered the odds of cavities progressing between teeth by 18% over 2 years. Trials reported no specific side effects. The product is made from milk protein.

Add to Bio HackChecked 2026-11-12
Status
Milk-derived ingredient sold in the US in topical dental pastes (MI Paste) and in Recaldent chewing gum. Not approved by the FDA as a drug for preventing cavities.
Also called
casein phosphopeptide amorphous calcium phosphate, casein phosphopeptide, CPP, ACP, CPP-ACFP, MI Paste, MI Paste Plus, Tooth Mousse, Tooth Mousse Plus, Recaldent, Recaldent gum
Taken for
white spots, white spot lesions, white spots from braces, enamel, remineralization, early cavities, cavities, tooth decay

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help2

Reported risks1

What people take it for, and what was found

Shown to help2

Moderate

White spot lesions and early enamel lesions

Shown to remineralize early enamel lesions more than placebo, without differing significantly from fluorides, in trials of 3 to 24 months.

The numbers and sources
Effect
In trials of 3 to 24 months, CPP-ACP remineralized early lesions more than placebo, and did not differ significantly from fluorides [1]. In clinical studies, light-induced fluorescence readings of white spot lesions improved against control or baseline (SMD -0.43, 95% CI -0.79 to -0.07) [2]. In orthodontic patients, Tooth Mousse (MI Paste) showed a tendency toward regression of white spot lesions [3], and CPP-ACP products reduced lesions around braces without differing from other fluoride products [4].
Population
8 randomized or quasi-randomized trials [1]. Clinical and in vitro studies of white spot lesions [2]. 12 clinical studies [3]. 11 controlled trials in patients with fixed braces, 9 randomized [4].
Sources
[1], [2], [3], [4]
Caveats
The orthodontic evidence was of limited quality [3]. The reviews used different outcome measures, and part of one pooled analysis came from laboratory studies [2].
Limited

Cavities between teeth: Recaldent gum

One trial found CPP-ACP gum lowered the odds of cavities between teeth by 18% over 24 months in 2,720 adolescents.

The numbers and sources
Effect
In 2,720 adolescents who chewed sugar-free gum with 54 mg CPP-ACP or the same gum without it for 10 minutes three times a day for 24 months, the odds of a tooth surface between teeth progressing to a cavity on X-ray were 18% lower with CPP-ACP (OR 0.82, p 0.03) [9]. In short in situ trials of 7 to 21 days, gum with 18.8 mg CPP-ACP raised enamel remineralization against gum without it (WMD -8.01, 95% CI -10.54 to -5.48) [10]. A review of CPP-ACP added to milk, gum or candy found remineralizing activity, mostly from in situ studies, and found clinical effects on cavity incidence not yet shown [11].
Population
Adolescents in 29 schools [9]. Volunteers wearing enamel samples in 5 in situ trials [10]. 16 studies, 2 in people and 14 in situ [11].
Sources
[9], [10], [11]
Caveats
One clinical trial, scored by a single examiner [9]. The abstract does not report funding.
Why limited
This rests on one trial, of 2,720 people. Strength counts independent studies that agree, so one trial is limited at any size.

Mixed results1

Moderate

Compared with or added to fluoride

Mixed results: some reviews found more remineralization with CPP-ACP than fluoride, while others found similar results and no clinically relevant gain from adding it.

The numbers and sources
Effect
Across 15 RCTs of white spot lesions, CPP-ACP plus fluoride did not differ from fluoride alone on laser fluorescence at 1 month (SMD -0.30, 95% CI -0.64 to 0.04), 3 months (SMD -0.47, 95% CI -1.02 to 0.07) or 6 months (SMD -0.49, 95% CI -1.13 to 0.15). Fluorescence favored fluoride alone at 3 months (MD 0.58, 95% CI 0.25 to 0.91), and lesion area favored the combination at 6 months (MD -0.38, 95% CI -0.72 to -0.04). The authors found none of these changes clinically relevant [5]. Against fluorides alone, one meta-analysis of 10 studies found more remineralization with CPP-ACP (WMD -2.47, 95% CI -3.62 to -1.32), with no difference in decayed, missing and filled surfaces or the enamel decalcification index [6]. Another review of 11 RCTs found conflicting evidence and similar clinical results [7]. A 2026 review found 5 of 13 CPP-ACP trials favored CPP-ACP over fluoride, and formulations with fluoride had slight advantages over CPP-ACP alone [8]. A 2015 review found no significant benefit of Tooth Mousse over brushing with fluoride toothpaste for preventing early decay [3].
Population
RCTs in people with white spot lesions or early enamel caries [5][6][7][8]. 395 participants in 10 studies [6].
Sources
[5], [6], [7], [8], [3]
Caveats
Certainty was very low [5], and most trials were at high or unclear risk of bias [7][8].

Doses studied

The gum trial used 54 mg CPP-ACP per piece, chewed three times a day for 24 months [9]. In situ gum trials used 10.0 or 18.8 mg [10]. Paste trials followed participants for 3 to 24 months [1].

Risks

Reported risks1

Limited

Milk protein allergy

The maker's instructions exclude people with milk protein allergies from Tooth Mousse, which is made from milk casein.

The numbers and sources
Effect
CPP-ACP is made from milk casein. A 2015 systematic review reports that the manufacturer's instructions indicate Tooth Mousse (MI Paste) for any age except people with milk protein allergies, and limit Tooth Mousse Plus (MI Paste Plus) to people over 6 because it contains fluoride [3].
Population
Product instructions, as reported in a systematic review [3].
Sources
[3]
Caveats
This is a product instruction, not a measured rate of allergic reactions.

Checked, no increase found1

Moderate

Side effects in trials

No specific or serious side effects of CPP-ACP were found in trials of 3 to 24 months, though reporting was limited.

The numbers and sources
Effect
No specific side effect of CPP-ACP was found across trials of 3 to 24 months [1]. No serious side effects were found in 10 trials against fluorides [6], and no adverse effect was found against fluorides in 11 RCTs [7].
Population
Trial participants [1][6][7].
Sources
[1], [6], [7]
Caveats
Trials were small and adverse event reporting was limited.

Claims tested and not found

  1. That adding CPP-ACP to fluoride improves white spot lesions. Laser fluorescence did not differ from fluoride alone at 1, 3 or 6 months, and no change was clinically relevant [5].
  2. That Tooth Mousse prevents early decay better than fluoride toothpaste. A systematic review of 12 studies found no significant benefit over brushing with fluoride toothpaste [3].

Sources

  1. Li J, Xie X, Wang Y, et al. Long-term remineralizing effect of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) on early caries lesions in vivo: a systematic review. Journal of Dentistry. 2014. https://doi.org/10.1016/j.jdent.2014.03.015
  2. Ma X, Lin X, Zhong T, Xie F. Evaluation of the efficacy of casein phosphopeptide-amorphous calcium phosphate on remineralization of white spot lesions in vitro and clinical research: a systematic review and meta-analysis. BMC Oral Health. 2019. https://doi.org/10.1186/s12903-019-0977-0
  3. Raphael S, Blinkhorn A. Is there a place for Tooth Mousse in the prevention and treatment of early dental caries? A systematic review. BMC Oral Health. 2015. https://doi.org/10.1186/s12903-015-0095-6
  4. Pithon MM, Baião FS, Sant'Anna LID, et al. Effectiveness of casein phosphopeptide-amorphous calcium phosphate-containing products in the prevention and treatment of white spot lesions in orthodontic patients: A systematic review. Journal of Investigative and Clinical Dentistry. 2019. https://doi.org/10.1111/jicd.12391
  5. Golzio Navarro Cavalcante B, Schulze Wenning A, Szabó B, et al. Combined Casein Phosphopeptide-Amorphous Calcium Phosphate and Fluoride Is Not Superior to Fluoride Alone in Early Carious Lesions: A Meta-Analysis. Caries Research. 2024. https://doi.org/10.1159/000533547
  6. Wu L, Geng K, Gao Q. Early Caries Preventive Effects of Casein Phosphopeptide-Amorphous Calcium Phosphate (CPP-ACP) Compared with Conventional Fluorides: A Meta-analysis. Oral Health & Preventive Dentistry. 2019. https://pubmed.ncbi.nlm.nih.gov/31825022/
  7. Rahmath Meeral P, Doraikannan S, Indiran MA. Efficiency of casein phosphopeptide amorphous calcium phosphate versus topical fluorides on remineralizing early enamel carious lesions: A systematic review and meta analysis. Saudi Dental Journal. 2024. https://doi.org/10.1016/j.sdentj.2024.01.014
  8. Mishra A, Sharan J, Sivakumar I. Remineralising efficacy of bioactive glass and casein phosphopeptide amorphous calcium phosphate in white spot lesions or early enamel caries: A systematic review of randomised controlled trials. Japanese Dental Science Review. 2026. https://doi.org/10.1016/j.jdsr.2026.05.004
  9. Morgan MV, Adams GG, Bailey DL, et al. The anticariogenic effect of sugar-free gum containing CPP-ACP nanocomplexes on approximal caries determined using digital bitewing radiography. Caries Research. 2008. https://doi.org/10.1159/000128561
  10. Yengopal V, Mickenautsch S. Caries preventive effect of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP): a meta-analysis. Acta Odontologica Scandinavica. 2009. https://doi.org/10.1080/00016350903160563
  11. Giacaman RA, Maturana CA, Molina J, et al. Effect of Casein Phosphopeptide-Amorphous Calcium Phosphate Added to Milk, Chewing Gum, and Candy on Dental Caries: A Systematic Review. Caries Research. 2023. https://doi.org/10.1159/000530638

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