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Comparative evaluation of cow beta-casein variants (A1/A2) consumption on Th2-mediated inflammatory response in mouse gut.

Haq MR, Kapila R, Sharma R, Saliganti V, Kapila S. (2013) Eur J Nutr.  2013 Oct 29. [Epub ahead of print] 

Web URL: View this and related abstracts via PubMed here

Abstract:

PURPOSE:

Recently, apprehension has been raised regarding "A1/A2 hypothesis" suggesting relationship between consumption of A1 "like" variantsof cow β-casein and various physiological disorders. The information available is based on either the human epidemiological data of milk consumption or in vitro trials on cell lines with β-casomorphin peptides. The direct scientific evidence establishing the link between consumption of A1/A2 "like" milk and health is scanty. Thus, under present investigation, in vivo trials in mice were undertaken to study the effect of feeding three genetic variants(A1A1, A1A2 and A2A2) of cow β-casein milk on gastrointestinal immune system as it is the first and foremost site of immunological interactions.

METHODS:

Animals were divided into four groups for feeding with basal diet (control) and β-casein isolated from milk of genotyped (A1A1, A1A2 and A2A2) dairy animals, respectively. Gut immune response was analyzed by spectrophotometric assessment of MPO activity, quantitative sandwich ELISA of inflammatory cytokines (MCP-1 and IL-4), antibodies (total IgE, IgG, sIgA, IgG1 and IgG2a) and qRT-PCR of mRNA expression for toll-like receptors (TLR-2 and TLR-4). Histological enumeration of goblet cells, total leukocytes and IgA+ cells was also carried out.

RESULTS:

It was observed that consumption of A1 "like" variants (A1A1 and A1A2) significantly increased (p < 0.01) the levels of MPO, MCP-1, IL-4, total IgE, IgG, IgG1, IgG2a and leukocyte infiltration in intestine. TLR-2 and TLR-4 mRNA expression was also up-regulated (p < 0.01) on administration of A1 "like" variants. However, no changes in sIgA, IgA+ and goblet cell numbers were recorded on consumption of any of the β-caseinvariants.

CONCLUSION:

It is reasonable to conclude that consumption of A1 "like" variants of β-casein induced inflammatory response in gut by activating Th2pathway as compared to A2A2 variants. The present study thus supports the purported deleterious impacts of consumption of A1 "like" variants of β-casein and suggests possible aggravation of inflammatory response for etiology of various health disorders.

FAB RESEARCH COMMENT:

In this animal study, consumption of A1 beta-casein (found in standard cows' milk) vs A2 beta-casein (the form found in human and other mammal milks) led to significant increases in a wide range of biochemical measures of gut inflammation.

These findings still require confirmation in human studies, but they are consistent with the proposal that adverse reactions to the A1 beta-casein found in standard cows' milk may be the cause of digestive and other health symptoms in sensitive individuals.

For more information on the differences between A1 and A2 beta-casein, see:
UPDATE 2015 - Human studies

Two clinical trials in humans have now been published since this study, each with findings that support the proposition that A1 beta-casein (found in standard cows' milk) causes gut and digestive symptoms when compared with A2.  See: