Systematic Review of the Gastrointestinal Effects of A1 Compared with A2 β-Casein
- PMID: 28916574
- PMCID: PMC5593102
- DOI: 10.3945/an.116.013953
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.
Keywords: gastrointestinal tract; humans; in vitro; in vivo; inflammation; milk; β-casein; β-casomorphin.
© 2017 American Society for Nutrition.
Conflict of interest statement
Author disclosures: NK, no conflicts of interest. SB-T previously consulted for the a2 Milk Company (Australia) Pty. Ltd. as an independent scientific adviser on food-labeling compliance matters, including undertaking a systematic review to meet Australia New Zealand food regulatory requirements related to health claims on food products. KD received an honorarium from the A2 Corporation to attend a meeting and grant support for an independent project. KW consulted for the A2 Corporation as an independent scientific adviser. This is a free access article, distributed under terms (http://www.nutrition.org/publications/guidelines-and-policies/license/) that permit unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Figures
Similar articles
-
Effects of milk containing only A2 beta casein versus milk containing both A1 and A2 beta casein proteins on gastrointestinal physiology, symptoms of discomfort, and cognitive behavior of people with self-reported intolerance to traditional cows' milk.Nutr J. 2016 Apr 2;15:35. doi: 10.1186/s12937-016-0147-z. Nutr J. 2016. PMID: 27039383 Free PMC article. Clinical Trial.
-
Comparative evaluation of cow β-casein variants (A1/A2) consumption on Th2-mediated inflammatory response in mouse gut.Eur J Nutr. 2014 Jun;53(4):1039-49. doi: 10.1007/s00394-013-0606-7. Epub 2013 Oct 29. Eur J Nutr. 2014. PMID: 24166511
-
Milk Intolerance, Beta-Casein and Lactose.Nutrients. 2015 Aug 31;7(9):7285-97. doi: 10.3390/nu7095339. Nutrients. 2015. PMID: 26404362 Free PMC article. Review.
-
Comparative effects of A1 versus A2 beta-casein on gastrointestinal measures: a blinded randomised cross-over pilot study.Eur J Clin Nutr. 2014 Sep;68(9):994-1000. doi: 10.1038/ejcn.2014.127. Epub 2014 Jul 2. Eur J Clin Nutr. 2014. PMID: 24986816 Clinical Trial.
-
The A2 milk case: a critical review.Eur J Clin Nutr. 2005 May;59(5):623-31. doi: 10.1038/sj.ejcn.1602104. Eur J Clin Nutr. 2005. PMID: 15867940 Review.
Cited by 8 articles
-
Randomised Controlled Trial: Partial Hydrolysation of Casein Protein in Milk Decreases Gastrointestinal Symptoms in Subjects with Functional Gastrointestinal Disorders.Nutrients. 2020 Jul 18;12(7):2140. doi: 10.3390/nu12072140. Nutrients. 2020. PMID: 32708428 Free PMC article.
-
A Comprehensive Evaluation of the Impact of Bovine Milk Containing Different Beta-Casein Profiles on Gut Health of Ageing Mice.Nutrients. 2020 Jul 19;12(7):2147. doi: 10.3390/nu12072147. Nutrients. 2020. PMID: 32707687 Free PMC article.
-
Evaluation of breath, plasma, and urinary markers of lactose malabsorption to diagnose lactase non-persistence following lactose or milk ingestion.BMC Gastroenterol. 2020 Jun 29;20(1):204. doi: 10.1186/s12876-020-01352-6. BMC Gastroenterol. 2020. PMID: 32600320 Free PMC article.
-
Oral Feeding of Cow Milk Containing A1 Variant of β Casein Induces Pulmonary Inflammation in Male Balb/c Mice.Sci Rep. 2020 May 15;10(1):8053. doi: 10.1038/s41598-020-64997-z. Sci Rep. 2020. PMID: 32415285 Free PMC article.
-
Frequencies Evaluation of β-Casein Gene Polymorphisms in Dairy Cows Reared in Central Italy.Animals (Basel). 2020 Feb 5;10(2):252. doi: 10.3390/ani10020252. Animals (Basel). 2020. PMID: 32033348 Free PMC article.
References
-
- Australia New Zealand Food Standards Code. Schedule 6—required elements of a systematic review [Internet]. 2015. Australian Government Gazette No. FSC 96 of 10 April 2015. [cited 2017 Jun 21]. Available from: https://www.legislation.gov.au/Details/F2015L00476.
-
- Kamiński S, Cieslińska A, Kostyra E. Polymorphism of bovine beta-casein and its potential effect on human health. J Appl Genet 2007;48:189–98. - PubMed
-
- De Noni RJ, FitzGerald HJT, Korhonen Y, Le Roux CT, Livesey I, Thorsdottir D, Tomé RW. Scientific report of EFSA prepared by a DATEX working group on the potential health impact of β-casomorphins and related peptides. EFSA Sci Rep 2009;231:1–107.
-
- Truswell AS. The A2 milk case: a critical review. Eur J Clin Nutr 2005;59:623–31. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
-
Full Text Sources
-
Miscellaneous