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

Noni, Ivano De; Fitzgerald, Richard J.; Korhonen, Hannu J. T.; Roux, Yves Le; Livesey, Caitlin; Þórsdóttir, Inga; Tomé, Daniel; Witkamp, R.F.

doi:10.2903/j.efsa.2009.231r

Cited by 56 publications

(22 citation statements)

References 485 publications

(471 reference statements)

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“…In this case, the CMs showed different receptor affinities. In another work by Noni et al, BCM-7 is described as a weak opioid receptor agonist [50]. Furthermore, BCM-7 and the phosphopeptide β-casein f(1-25)4P have been shown to induce apoptosis of HL-60 cells (promyeloic leukemia) [30].…”

Section: Milk Proteins and Processed Peptides With Chemopreventive Propertiesmentioning

confidence: 99%

Potential Protective Protein Components of Cow’s Milk against Certain Tumor Entities

et al. 2021

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Milk and dairy products, especially from cow’s milk, play a major role in the daily human diet. It is therefore hardly surprising that the subject of milk is being extensively researched and that many effects of individual milk components have been characterized as a result. With the wealth of results available today, the influence of milk on the development of various types of cancer and, in particular, its often protective effects have been shown both in vitro and in vivo and in the evaluation of large-scale cohort and case-control studies. Various caseins, diverse whey proteins such as α-lactalbumin (α-LA), bovine α-lactalbumin made lethal to tumor cells (BAMLET), β-lactoglobulin (β-LG), or bovine serum albumin (BSA), and numerous milk fat components, such as conjugated linoleic acid (CLA), milk fat globule membrane (MFGM), or butyrate, as well as calcium and other protein components such as lactoferrin (Lf), lactoferricin (Lfcin), and casomorphines, show antitumor or cytotoxic effects on cells from different tumor entities. With regard to a balanced and health-promoting diet, milk consumption plays a major role in a global context. This work provides an overview of what is known about the antitumoral properties of proteins derived from cow’s milk and their modes of action.

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Section: Milk Proteins and Processed Peptides With Chemopreventive Propertiesmentioning

confidence: 99%

Potential Protective Protein Components of Cow’s Milk against Certain Tumor Entities

et al. 2021

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“…Relatively little is known on the mechanisms of transfer of intact peptides longer than three amino acids through the intestinal mucosa. In specific situations (i.e., stress, diseases or aggression), both animals and humans display increased intestinal permeability [25]. In particular, the gut of neonates is almost permeable to proteins explaining the high level of β-CM7 at B2 ( Figure 6).…”

Section: β-Casomorphin-7 Level In Plasma Of Calves After A1-or A2-milmentioning

confidence: 99%

“…For opioid activity in the central nervous system after oral ingestion, the passage of A1-milk derived β-CM7 through the intestinal mucosa, and moreover through the bloodbrain-barrier, is needed [25]. However, the mechanisms of the transfer of intact peptides longer than tripeptides across the intestinal barrier are mostly unclear.…”

Section: Introductionmentioning

confidence: 99%

Comparative Effects of Milk Containing A1 versus A2 β-Casein on Health, Growth and β-Casomorphin-7 Level in Plasma of Neonatal Dairy Calves

Hohmann

Yin

Schweizer

et al. 2020

Animals

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Research has shown that digestion of A1 β-casein (β-CN) affects gastrointestinal motility and opioid activity through the release of the peptide β-casomorphin-7 (β-CM7). In the case of the A2 variant, the cleavage of β-CM7 does not occur or occurs at a very low rate. Therefore, the aim of the study was to compare the effects of milk containing either homozygote A1 or A2 β-CN on health and growth parameters of dairy calves. Forty-seven neonatal calves (24 females, 23 males) of the breeds German Holstein (GH, n = 9), German Simmental (GS, n = 33) and their crossing (GH × GS, n = 5) were used in a 21-day feeding study. Fecal score (FS), respiratory frequency (RF), and rectal body temperature (BT) were recorded daily, whereas body weight was measured at birth and at day 21 to estimate the average daily weight gain (ADG). Additionally, blood was collected from calves three times during the experimental period and, for the first time, the respective plasma samples were analyzed for intact β-CM7. Consumption of A2-milk led to a lower daily milk intake (dMI) (p < 0.05). Furthermore, fecal consistency was softer for calves fed A2-milk (p < 0.05). Although 44% of A2-calves had diarrhea or revealed a tendency towards it (FS ≥ 3), A1-calves had a prevalence of 21%. Calves with a FS of 4 were offered an electrolyte solution and received a dietary food supplement for the stabilization of the fluid and electrolyte balance. Nevertheless, similar ADG and end weights (EW) of calves fed A1- or A2-milk (p > 0.05) indicate that A2-milk may compensate higher diarrhea rates and lower dMI due to the associated higher protein content. This is the first report of intact β-CM7 in plasma of calves fed milk of either A1 or A2 β-CN. Evidence from this study suggests that due to the change in the amino-acid sequence, A2-milk might be able to prevent or, at least, to minimize the cleavage of β-CM7 in calves.

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“…In the last few decades, the scientific community has shown increasing interest in the potential impact of BCM-7 and the related peptides on human health. In 2009, an EFSA scientific report concluded that the available data were insufficient to suggest a cause-effect relationship between BCMs and non-communicable disorders, such as cardiovascular disease, autism and insulin dependent diabetes mellitus ( 4 ). Four systematic reviews on A1 and A2 β-CN consumption and health-related outcomes have been conducted so far ( 1 , 5 – 7 ).…”

Section: Introductionmentioning

confidence: 99%

A2 Milk and BCM-7 Peptide as Emerging Parameters of Milk Quality

et al. 2022

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Beta-casein makes up about 30% of the total protein contained in milk and can be present in cows' milk in two distinct forms (A1 or A2) or as a combination of the two. The only difference between these two variants of β-casein (β-CN) is a single amino acid substitution. This results in a different behavior of the protein upon enzymatic cleavage, following human consumption or due to microbial action. In most of the commercially available milk containing A1 or A1/A2 β-CN variants, the β-casomorphin-7 peptide (BCM-7) is released upon digestion and during cheese manufacturing/ripening, while this does not happen with A2 milk. BCM-7 is a known μ-opioid receptor agonist that may influence the gastro-intestinal physiology directly and may also exert effects elsewhere in the body, such as on the cardiovascular, neurological and endocrine systems. The present article is aimed at a revision of prior review papers on the topic, with a focus on the impact of ingestion of A1 β-CN milk and A2 β-CN milk on any health-related outcomes and on the impact of A1 or A2 β-CN variant on technological properties of cows' milk. When systematic reviews were considered, it was possible to conclude that A2 β-CN exerts beneficial effects at the gastrointestinal level compared with A1 β-CN, but that there is no evidence of A1 β-CN having negative effects on human health. Physicochemical differences among cows' milk containing either β-CN A2 or β-CN A1 and their effects on technological properties are discussed.

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

Cited by 56 publications

References 485 publications

Potential Protective Protein Components of Cow’s Milk against Certain Tumor Entities

Potential Protective Protein Components of Cow’s Milk against Certain Tumor Entities

Comparative Effects of Milk Containing A1 versus A2 β-Casein on Health, Growth and β-Casomorphin-7 Level in Plasma of Neonatal Dairy Calves

A2 Milk and BCM-7 Peptide as Emerging Parameters of Milk Quality

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