Casein peptides

Casomorphins (β-casomorphin-7, BCM-7), casein phosphopeptides (CPP), lactotripeptides Ile-Pro-Pro (IPP) and Val-Pro-Pro (VPP), α-casozepine (αS1-casein tryptic hydrolysate, "Lactium"), casokinins

Food-derived & nutrition

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Summary

Class: Food-derived peptides released from the four caseins (αS1, αS2, β, κ) by digestion, fermentation or enzymatic hydrolysis
Mechanism: IPP/VPP inhibit ACE; casomorphins are weak opioid-receptor agonists; CPP bind calcium; α-casozepine binds GABA-A receptors in vitro (benzodiazepine-like)
Routes studied: Oral (fermented milk drinks, hydrolysate capsules, fortified foods)
Dose range reported: Human trials: IPP+VPP 2–10 mg/day combined (fermented milk or tablets); α-casozepine 150–300 mg/day; CPP 1–3 g/day in calcium-absorption studies. BCM-7 is studied as a dietary exposure (from A1 β-casein milk), not as a supplement
Half-life: IPP and VPP are detectable in plasma for 1–2 h after ingestion at picomolar levels; casomorphins are rapidly degraded by DPP-4
Storage: Dry capsules: room temperature. Fermented milk products: refrigerate
Regulatory status: Food ingredients / supplements; no medicinal approval; EFSA rejected IPP/VPP blood-pressure claims

Doses are as reported in studies or by the community — never recommendations.

1What it is

Casein is about 80% of milk protein and, like whey, is a reservoir of hidden bioactive sequences. Four families matter in practice: - Lactotripeptides IPP and VPP from β- and κ-casein, released when milk is fermented with Lactobacillus helveticus. Sold in Japan since the 1990s as blood-pressure-lowering fermented milk (Calpis "Ameal S") and later as tablets. - β-Casomorphins, especially BCM-7, released from the A1 variant of β-casein during digestion. These are the basis of the "A1 versus A2 milk" debate. - Casein phosphopeptides (CPP), phosphoserine-rich fragments that bind calcium and are used in dental remineralising products (CPP-ACP, "Recaldent") and as calcium-absorption enhancers. - α-Casozepine, a decapeptide from αS1-casein marketed as a calming ingredient for humans and, more widely, for cats and dogs. All are natural digestion products; everyone who drinks milk is exposed to them.

2How it's thought to work

IPP/VPP. inhibit ACE with IC50 values in the low micromolar range; may also improve endothelial function independently of ACE. Plasma concentrations reached after a food dose are far below in-vitro IC50s, so the mechanism in humans is debated (Foltz 2007).

Casomorphins. μ-opioid agonism in the gut slows transit and may affect mucus secretion; proposed effects on the brain require crossing the blood–brain barrier, which is poorly supported.

CPP. keep calcium soluble in the gut and stabilise amorphous calcium phosphate on tooth enamel.

α-Casozepine. binds GABA-A receptors in vitro at the benzodiazepine site, without sedation in animal models (Miclo 2001).

Fragments released when casein is digested, including sequences reported to inhibit ACE. Human blood-pressure trials show small and inconsistent effects.Schematic — not to scale

3What the research shows

Graded A (small effect)

Blood pressure (IPP/VPP)

The original Japanese trial of fermented milk with IPP/VPP reported ~14/7 mmHg reductions in 30 hypertensive adults (Hata 1996, Am J Clin Nutr). Later European trials were mostly null (Engberink 2008; van der Zander 2008). Meta-analyses pooling ~30 trials find a small average reduction of roughly 3–4 mmHg systolic, larger in Japanese cohorts than in Europeans (Cicero 2013, Br J Nutr; Fekete 2015, Nutrients). EFSA concluded in 2009 and again in 2012 that a cause-and-effect relationship was not established. [1][2][3][4][5]

Graded A/B

Stress and anxiety (α-casozepine)

Small randomised crossover trials in healthy volunteers reported reduced blood pressure and cortisol responses to a mental stress test and improved subjective anxiety at 150–400 mg (Messaoudi 2005, Eur J Nutr; Kim 2007 in stressed women). Trials are small, manufacturer-linked and use surrogate stress outcomes; no trials in diagnosed anxiety disorders. Veterinary trials in cats and dogs are the larger literature. [6]

Graded A (dental); B (bone)

Calcium absorption and dental remineralisation (CPP)

CPP-ACP toothpastes and chewing gums have reasonable support for enamel remineralisation and reduction of white-spot lesions (Reynolds 2008; systematic reviews with moderate certainty). Oral CPP for calcium absorption or bone density: EFSA rejected the claim (2009); human data inconsistent. [5][9]

Graded B (gut symptoms); D (autism, diabetes, heart disease)

A1/A2 milk and casomorphins

Small crossover trials report that A2-only milk causes fewer gastrointestinal symptoms and less post-dairy inflammation than conventional milk in people with self-reported intolerance (Jianqin 2016, Nutr J; He 2017), funded by the A2 Milk Company. Epidemiological hypotheses linking BCM-7 to type 1 diabetes, heart disease or autism have not been supported by controlled evidence; EFSA (2009) found no cause-and-effect relationship. [5][8]

Graded C/D

Casokinins, antithrombotic and immunomodulatory peptides

Cell and rodent studies only.

4Reported side effects and interactions

Literature-reported

IPP/VPP products well tolerated in trials. α-Casozepine: no sedation or dependence reported in trials; mild GI complaints. CPP products: well tolerated; CPP-ACP contains milk protein (allergy consideration).

Community-reported

constipation attributed to casomorphins (plausible via gut opioid receptors); "dairy brain fog" reports are anecdotal.

Theoretical. opioid-receptor activity of casomorphins in infants or people with impaired DPP-4; all casein products are unsuitable in cow's milk protein allergy.

Interactions. IPP/VPP additive with antihypertensives in theory (small); α-casozepine with benzodiazepines or sedatives has not been studied.

Markers researchers commonly monitor

Marker	Why it's watched
Home blood pressure (morning and evening)	the only way to see whether a 3 mmHg population effect means anything for an individual.
Salivary or serum cortisol under a standard stressor	the α-casozepine trial outcome; rarely practical, so a stress diary is the realistic proxy.
GI symptom log	for A1/A2 or casomorphin questions; a blinded milk swap at home is more informative than any blood test.
Dental examination	for CPP-ACP, enamel changes are assessed by a dentist, not self-monitored.
No compound-specific blood markers are established

Free for everyone. Safety information is never behind a paywall.

5Formulation and handling

IPP/VPP are supplied as fermented milk drinks or standardised tablets (a labelled mg amount of the two peptides). α-Casozepine comes as capsules standardised to the hydrolysate, not to the decapeptide itself. CPP-ACP appears in toothpaste and gum. Fermented products need refrigeration; tablets and capsules store at room temperature. No calculator applies.

6Commonly studied alongside

Whey-derived peptides (profile 172), lactokinins, potassium and DASH-style diets (blood pressure context), L-theanine and GABA (stress context), fluoride (dental context).

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Food / dietary supplement ingredients; CPP-ACP is a cosmetic/dental ingredient; no approved drug claims
European Union	Food / food supplement; EFSA rejected IPP/VPP blood-pressure claims (2009, 2012) and CPP calcium claims; Lactium has Novel Food status as a food ingredient †
United Kingdom	As EU
Australia	Food; CPP-ACP developed in Melbourne and widely sold in dental products
South Africa	Food / complementary medicine depending on claims †
Sport	Not prohibited by WADA

8Open questions

Why IPP/VPP trials succeed in Japan and fail in Europe: diet, genetics, BP or publication bias?
Whether α-casozepine's GABA-A binding translates to any central effect in humans.
Whether BCM-7 crosses the adult blood–brain barrier in meaningful amounts.

9References

1Hata Y et al. (1996). A placebo-controlled study of the effect of sour milk on blood pressure in hypertensive subjects. Am J Clin Nutr. PubMed · DOI
2Cicero AFG et al. (2013). Blood pressure lowering effect of lactotripeptides assumed as functional foods: a meta-analysis of current available clinical trials. J Hum Hypertens [verify journal]. PubMed
3Fekete ÁA, Givens DI, Lovegrove JA (2015). Casein-derived lactotripeptides reduce systolic and diastolic blood pressure in a meta-analysis of randomised clinical trials. Nutrients. PubMed · DOI
4Engberink MF et al. (2008). Lactotripeptides show no effect on human blood pressure: results from a double-blind randomized controlled trial. Hypertension. PubMed · DOI
5EFSA NDA Panel (2009). Review of the potential health impact of β-casomorphins and related peptides. EFSA Scientific Report. PubMed
6Messaoudi M et al. (2005). Effects of a tryptic hydrolysate from bovine milk αS1-casein on hemodynamic responses in healthy human volunteers facing successive mental and physical stress situations. Eur J Nutr. PubMed · DOI
7Miclo L et al. (2001). Characterization of α-casozepine, a tryptic peptide from bovine αS1-casein with benzodiazepine-like activity. FASEB J. PubMed · DOI
8Jianqin S et al. (2016). Effects of milk containing only A2 beta casein versus milk containing both A1 and A2 beta casein proteins on gastrointestinal physiology, symptoms of discomfort, and cognitive behavior of people with self-reported intolerance to traditional cows' milk. Nutr J. PubMed · DOI
9Reynolds EC (2008). Calcium phosphate-based remineralization systems: scientific evidence? Aust Dent J. PubMed · DOI

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

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11Page history

31 Oct 2026Profile published — awaiting medical review

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