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Review of the potential health impact of β-casomorphins and related peptides 1

Report of the DATEX Working Group on β-casomorphins

(Question N° EFSA-Q-2008-379) Issued on 29 January 2009


Ivano De Noni, Richard J. FitzGerald, Hannu J. T. Korhonen, Yves Le Roux, Chris T.

Livesey, Inga Thorsdottir, Daniel Tomé, Renger Witkamp.


A1ミルク・・・βカゼインA1を多く含む牛乳 A2ミルク・・・βカゼインA2を多く含む牛乳の事。



Among these, β-casomorphin-7 (BCM7), a peptidesequence present in the milk protein β-casein, has been suggested to contribute to an increased risk for certain non-communicable diseases, such as autism, cardiovascular diseases and type I diabetes.

Some literature reports have proposed possible mechanistic explanations for such associations Recognising the alleged negative effect of BCM7 on human health, EFSA deemed it necessary to perform a comprehensive review of the published scientific literature in order to assess the relationship of this peptide and related peptides with non-communicable diseases.


However, there are indications that the sequential action of several digestive enzymes may be involved and the formation of certain BCMs after SGID (with multiple enzyme activities) has been demonstrated.

Animal data clearly indicate that BCMs, including BCM7, can act as opioid receptor agonists, probably acting via μ-type opioid receptors. However, in most if not all animal studies to date, in vivo opioid effects for BCM7 and related milk-derived peptides have only been observed following intra-peritoneal (i.p.) or intra-cerebro-ventricular (i.c.v.) administration.


A prerequisite for opioid activity after oral ingestion is that the peptides must pass the intestinal epithelial barrier. In addition, subsequent biotransformation in the liver and stability in plasma may be factors determining the ultimate biological activity.

Finally, passage through the blood-brain-barrier is in principle needed for an activity in the central nervous system.

Relatively little is known on the mechanisms of transfer of intact peptides longer than 3 amino acids across the intestinal barrier. If this transport occurs, then the extent is very low and passive diffusion is the most likely transfer mechanism.

The presence of β-casomorphin immunoreactive material has been reported in blood in two studies with neonatal dogs and calves.

However, the presence of intact β-casomorphin molecules in blood after intake of milk or casein has not been established in in vivo studies.


Based on the present review of available scientific literature, a cause-effect relationship between the oral intake of BCM7 or related peptides and etiology or course of any suggested non-communicable diseases cannot be established. Consequently, a formal EFSA risk assessment of food-derived peptides is not recommended.