Systematic Review of the Gastrointestinal Effects of A1 Compared with A2 β-Casein

Abstract

This is the first systematic review, to our knowledge, of published studies investigating the gastrointestinal effects of A1-type bovine β-casein (A1) compared with A2-type bovine β-casein (A2). The review is relevant to nutrition practice given the increasing availability and promotion in a range of countries of dairy products free of A1 for both infant and adult nutrition. In vitro and in vivo studies (all species) were included. In vivo studies were limited to oral consumption. Inclusion criteria encompassed all English-language primary research studies, but not reviews, involving milk, fresh-milk products, β-casein, and β-casomorphins published through 12 April 2017. Studies involving cheese and fermented milk products were excluded. Only studies with a specific gastrointestinal focus were included. However, inclusion was not delimited by specific gastrointestinal outcome nor by a specific mechanism. Inclusion criteria were satisfied by 39 studies. In vivo consumption of A1 relative to A2 delays intestinal transit in rodents via an opioid-mediated mechanism. Rodent models also link consumption of A1 to the initiation of inflammatory response markers plus enhanced Toll-like receptor expression relative to both A2 and nonmilk controls. Although most rodent responses are confirmed as opioid-mediated, there is evidence that dipeptidyl peptidase 4 stimulation in the jejunum of rodents is via a nonopioid mechanism. In humans, there is evidence from a limited number of studies that A1 consumption is also associated with delayed intestinal transit (1 clinical study) and looser stool consistency (2 clinical studies). In addition, digestive discomfort is correlated with inflammatory markers in humans for A1 but not A2. Further research is required in humans to investigate the digestive function effects of A1 relative to A2 in different populations and dietary settings.

Artificial intelligence identified peptides modulate inflammation in healthy adults

“…41,42 For example, dietary A1 β-casein peptides were associated with inflammatory markers in humans. 43 β-Casein peptides modulated immunoglobulins and cytokines through the gut, but in contrast to our study, effects on IL-6 were not reported. Additionally, multiple protein hydrolysates were found to affect Toll-like receptors (TLRs), but the effects were mostly hydrolysate-dependent rather than focused on individual peptides.…”

Evaluation of candidate gene effects and environmental factors on reproductive performance of Holstein cows

“…CSN2 variants play an important role in milk and cheese yield/quality and their concentration is positively associated with good rennet properties of milk (Massella et al, 2017). Moreover, A2 milk (A1 free) is produced in many different countries, claiming its potential benefits in human health (Caroli et al, 2016;Brooke-Taylor et al, 2017), but the studies about positive effects of A2 milk or unfavourable effects of A1 milk are often conflicting. Apart from the contradictory human health studies about CSN2 genotypes (A1/A2), there is still a strong need for the evaluation of corresponding genotype effects on cow fertility and reproduction performance.…”

SNP-based quantitative deconvolution of biological mixtures: application to the detection of cows with subclinical mastitis by whole genome sequencing of tank milk

“…This information may be very useful both from a farm health management point of view as well as from a downstream dairy processing point of view. Whole genome sequence data of bulk milk also informs about the herd frequency of functional variants such casein variants affecting consumer health or processing properties 10 , or variants causing inherited defects or embryonic lethality in cows 4 . In many countries, it is not allowed to add milk from cows being treated with antibiotics to the tank.…”