What it is
Casein phosphopeptides (CPPs) are short pieces of milk protein that hold on to calcium. When casein — the main protein in milk — is digested with enzymes, some of the fragments released carry clusters of phosphorylated serine (phosphoserine) and other acidic amino acids. Those clusters bind calcium and keep calcium phosphate from falling out of solution (Cochrane and Reynolds, Adv Dent Res 2012, PMID 22899678).
When the peptides are combined with calcium phosphate, the result is CPP-ACP — casein phosphopeptide–amorphous calcium phosphate — a nanocomplex sold under the trade name RECALDENT. "Amorphous" means the calcium phosphate is not yet crystallised, so it can release calcium and phosphate ions.
It is a family of peptides, not a single molecule with one sequence. What the family shares is the calcium-binding cluster.
How it is meant to work on teeth
The University of Melbourne group that developed CPP-ACP describes it as a "salivary biomimetic": saliva and milk both use phosphorylated proteins to keep calcium and phosphate dissolved, and CPP-ACP "can stabilize even higher concentrations of calcium and phosphate than milk" (PMID 22899678). They compare it to statherin, a phosphorylated peptide in saliva that does the same job.
The idea is that the peptides carry calcium and phosphate to the tooth surface and keep them available where enamel has started to lose mineral — a white-spot lesion, the chalky patch that is the earliest visible stage of decay. That mechanism comes from laboratory chemistry; what happens in mouths is the question the trials ask.
What the trials show
The record is large but made of small studies. PubMed tags 148 randomised controlled trials of CPP-ACP or casein phosphopeptides, and ClinicalTrials.gov lists 78 registered studies (2026-11-03).
The most direct test of what CPP-ACP adds is to compare it with fluoride against fluoride alone, because fluoride is the established treatment. A 2024 meta-analysis did exactly that (Cavalcante et al., Caries Research, PMID 37883928; PROSPERO CRD42021286245):
| Measure | What the pooled randomised trials found |
|---|---|
| Laser fluorescence at 1, 3, 6 months | No significant difference between CPP-ACP + fluoride and fluoride alone |
| Light-induced fluorescence (QLF) | No difference at 1 and 6 months; at 3 months, values favoured fluoride alone |
| Lesion area at 6 months | A small difference favouring CPP-ACP + fluoride (MD −0.38) |
| Authors' overall reading | "None of these observed changes indicated substantial clinical relevance"; certainty of evidence very low |
Searched from 21 studies, 15 entered the numbers. Other syntheses — network meta-analyses of white-spot treatments in orthodontic patients and of root-caries treatments (2026) — include CPP-ACP among many agents; their rankings are comparisons of products and are not reproduced here. This entry reports the molecule and the shape of its evidence, not a verdict on any paste.
Allergy and safety
CPP-ACP is made from milk. The maker's product page puts it plainly: "RECALDENT (CPP-ACP) is derived from milk casein. Do not use on patients with a milk protein or hydroxybenzoates allergy. In case of allergic reaction, stop use, rinse mouth with water, and seek medical advice." PubMed holds 14 records discussing CPP-ACP with allergy (2026-11-03). Whether a product suits a particular person is for their dentist to decide.
Where it stands
- Status: an ingredient in dental products, not an approved drug; the products are sold for professional and home dental use.
- Brand: GC's MI Paste contains RECALDENT (CPP-ACP); MI Paste Plus adds fluoride (GC America, read 2026-11-03).
- Research record: 931 PubMed records; 148 randomised trials; 78 registered studies (2026-11-03).
Related reading
Other peptides people take by mouth rather than by injection are described in the collagen peptides entry and, in the sweetener aisle, neotame. How a short fragment differs from the protein it came from is set out in peptide vs protein.