Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Aug 22;12(17):3151.
doi: 10.3390/foods12173151.

Difficulties in Establishing the Adverse Effects of β-Casomorphin-7 Released from β-Casein Variants-A Review

Marta Liliane de Vasconcelos  1 , Luisa Maria F S Oliveira  1 , Jeremy Paul Hill  2 , Ana Maria Centola Vidal  1
Affiliations
Review

Difficulties in Establishing the Adverse Effects of β-Casomorphin-7 Released from β-Casein Variants-A Review

Marta Liliane de Vasconcelos et al. Foods. .

Abstract

β-Casomorphin-7 (BCM-7) is a peptide released through the proteolysis of β-casein (β-CN), which is considered a bioactive peptide displaying evidence of promoting the binding and activation of the μ-opioid receptor located in various body parts, such as the gastrointestinal tract, the immune system and potentially the central nervous system. The possible effects of BCM-7 on health are a theme rising in popularity due to evidence found in several studies on the modulation of gastrointestinal proinflammatory responses that can trigger digestive symptoms, such as abdominal discomfort. With the advancement of studies, the hypothesis that there is a correlation of the possible effects of BCM-7 with the microbiota-gut-brain axis has been established. However, some studies have suggested the possibility that these adverse effects are restricted to a portion of the population, and the topic is controversial due to the small number of in vivo studies, which makes it difficult to obtain more conclusive results. In addition, a threshold of exposure to BCM-7 has not yet been established to clarify the potential of this peptide to trigger physiological responses at gastrointestinal and systemic levels. The proportion of the population that can be considered more susceptible to the effects of BCM-7 are evidenced in the literature review. The challenges of establishing the adverse effects of BCM-7 are discussed, including the importance of quantifying the BCM-7 release in the different β-CN genotypes. In summary, the reviewed literature provides plausible indications of the hypothesis of a relationship between β-CN A1/BCM-7 and adverse health effects; however, there is need for further, especially in vivo studies, to better understand and confirm the physiological effects of this peptide.

Keywords: casein; genotype; lactose intolerance; milk; opioid; β-Casomorphin.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Peptide binding of A1 and A2 β-CN and cleavage sites with BCM-7 and BCM-9 release during proteolysis.
Figure 2
Figure 2
Cleavage of BCM-7 between proline and phenylalanine residues in the peptide.
Figure 3
Figure 3
Potential interaction of BCM-7 in the microbiota–gut–brain axis.
See this image and copyright information in PMC

References

    1. Smith N.W., Fletcher A.J., Hill J.P., McNabb W.C. Modeling the Contribution of Milk to Global Nutrition. Front. Nutr. 2022;8:716100. doi: 10.3389/fnut.2021.716100. - DOI - PMC - PubMed
    1. Tulipano G. Role of Bioactive Peptide Sequences in the Potential Impact of Dairy Protein Intake on Metabolic Health. Int. J. Mol. Sci. 2020;21:8881. doi: 10.3390/ijms21228881. - DOI - PMC - PubMed
    1. Asledottir T., Le T.T., Poulsen N.A., Devold T.G., Larsen L.B., Vegarud G.E. Release of β-Casomorphin-7 from Bovine Milk of Different β-Casein Variants after Ex Vivo Gastrointestinal Digestion. Int. Dairy J. 2018;81:8–11. doi: 10.1016/j.idairyj.2017.12.014. - DOI
    1. Uzma S., Gill H., Chandrapala J. Casein Micelles as an Emerging Delivery System for Bioactive Food Components. Foods. 2021;10:1965. doi: 10.3390/foods10081965. - DOI - PMC - PubMed
    1. Hannelore D., Vohwinkel M., Rehner G. Effect of Casein and β-Casomorphins on Gastrointestinal Motility in Rats. J. Nutr. 1990;120:252–257. doi: 10.1093/jn/120.3.252. - DOI - PubMed