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Protein, malnutrition and wasting diseases

Comparative effects of A1 versus A2 beta-casein on gastrointestinal measures: a blinded randomised cross-over pilot study



At present, there is debate about the gastrointestinal effects of A1-type beta-casein protein in cows’ milk compared with the progenitor A2 type. In vitro and animal studies suggest that digestion of A1 but not A2 beta-casein affects gastrointestinal motility and inflammation through the release of beta-casomorphin-7. We aimed to evaluate differences in gastrointestinal effects in a human adult population between milk containing A1 versus A2 beta-casein.


Forty-one females and males were recruited into this double-blinded, randomised 8-week cross-over study. Participants underwent a 2-week dairy washout (rice milk replaced dairy), followed by 2 weeks of milk (750 ml/day) that contained beta-casein of either A1 or A2 type before undergoing a second washout followed by a final 2 weeks of the alternative A1 or A2 type milk.


The A1 beta-casein milk led to significantly higher stool consistency values (Bristol Stool Scale) compared with the A2 beta-casein milk. There was also a significant positive association between abdominal pain and stool consistency on the A1 diet (r=0.520, P=0.001), but not the A2 diet (r=−0.13, P=0.43). The difference between these two correlations (0.52 versus −0.13) was highly significant (P<0.001). Furthermore, some individuals may be susceptible to A1 beta-casein, as evidenced by higher faecal calprotectin values and associated intolerance measures.


These preliminary results suggest differences in gastrointestinal responses in some adult humans consuming milk containing beta-casein of either the A1 or the A2 beta-casein type, but require confirmation in a larger study of participants with perceived intolerance to ordinary A1 beta-casein-containing milk.

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This study was supported by a grant from A2 Dairy Products Australia, who also supplied the milk. A2 Dairy Products Australia had no role in the data analysis of this study.

Author contributions

All authors contributed to the research design (project conception, development of overall research plan and study oversight). SH and SP conducted the research (hands-on conduct of the experiments and data collection). KW analysed the data and performed statistical analyses. SK, KW, SH and SP wrote the paper. All authors had primary responsibility for the final content.

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Correspondence to S Pal.

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Competing interests

Dr Sonja Kukuljan is a salaried employee of A2 Dairy Products Australia. Professor Keith Woodford consults to A2 Corporation as an independent scientific adviser. The remaining authors declare no conflict of interest.

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Ho, S., Woodford, K., Kukuljan, S. et al. Comparative effects of A1 versus A2 beta-casein on gastrointestinal measures: a blinded randomised cross-over pilot study. Eur J Clin Nutr 68, 994–1000 (2014).

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