A1- and A2 beta-casein on health-related outcomes: a scoping review of animal studies

Abstract

Purpose Food-derived bioactive peptides may influence important physiological functions. An important example is beta-casomorphins, which are opioid peptides derived from A1 beta-casein in bovine milk and have been associated to be risk factors for non-communicable diseases in humans. A1 and A2 beta-casein are different with respect to the release of bioactive peptides, in particular BCM-7. However, evidence from human studies is limited and could be complemented with evidence derived from animal studies. We conducted a scoping review to identify animal studies investigating the effects of A1 beta-casein or BCM-7 compared to A2 beta-casein or any other intervention on health-related outcomes. Methods We systematically searched for relevant studies in two electronic databases (Medline, Embase; last search performed March 2020). Two reviewers independently undertook study selection and data extraction of included references. Results were summarized tabularly and narratively. Results We included 42 studies investigating various animal models, including rats, mice, rabbits, and dogs. Six studies investigated health-related outcomes of A1- vs. A2 milk, while most studies (n = 36) reported on physiological properties (e.g., analgesic effect) of BCM-7 as an opioid peptide. Included studies were extremely heterogeneous in terms of the study population, type of intervention and dose, and type of outcome measures. Conclusions Only a few studies comparing the effects of A1- and A2 milk were identified. More studies addressing this research question in animal models are needed to provide essential information to inform research gaps. Results from future studies could eventually complement research for humans, particularly when the body of evidence remains uncertain as is the case in the A1- and A2 milk debate.

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

“…As far as other health outcomes (CVD, diabetes, neurological diseases) are concerned, according to Kuellenberg de Gaudry and colleagues ( 6 ), the certainty of the evidence, according to the GRADE assessment, was judged as very low for most health outcomes considered in clinical trials and epidemiological studies published prior to October 2017. Using the same methodological approach, this was confirmed by Danilowsky and colleagues ( 1 ), for clinical trials and animal studies published prior to 2021 and for animal –based studies published prior to 2020 ( 7 ).…”

“…Despite the large range of evidence on the effects of food- derived opioids on delayed intestinal transit, intestinal inflammation, intestinal permeability and an altered microbiome, it is clear that, when analyzing the conclusions of the narrative reviews, considerable variability in evidence exists regarding the effect on non-communicable diseases. The four systematic reviews published between 2017 and 2021 ( 1 , 5 – 7 ) constitute a tool for interpreting such variability. These reviews were all conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist, with the aim of critically analyzing the existing data from well-controlled human clinical trials and animal studies on the impact of ingestion of A1 β-CN milk and A2 β-CN milk on health-related outcomes.…”

“…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 ). All of them concluded that the consumption of A2 β-CN milk may benefit the gastrointestinal status when compared to A1 β-CN milk, however the evidence about other health benefits was inconclusive ( 1 , 5 – 7 ).…”

“…Four systematic reviews on A1 and A2 β-CN consumption and health-related outcomes have been conducted so far ( 1 , 5 – 7 ). All of them concluded that the consumption of A2 β-CN milk may benefit the gastrointestinal status when compared to A1 β-CN milk, however the evidence about other health benefits was inconclusive ( 1 , 5 – 7 ).…”

A2 Milk: New Perspectives for Food Technology and Human Health

“…Although related reviews have gathered a large amount of scientific evidence, the role of β-casomorphins (BCMs), such as BCM-7, and their physiological functions remain controversial, and more research with improved diagnostic techniques is needed to unequivocally determine their mechanism of action and study their possible health-related impacts [ 22 ]. Recently, other reviews [ 15 , 58 , 59 , 60 ] concluded that human-based published evidence provided moderate certainty for the adverse digestive health effects of A1 β-casein compared with A2 β-casein, but only indications and not conclusive evidence for the relation with other health effects. Globally, the adverse effects of BCM-7 on health have obtained positive results when experimental animal models were used for their study.…”