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A2 and A2 milk protein - frequently asked Q&As

milk

Date: 2021

Answers to frequently asked questions on A2 milk protein


1)    What proteins are found in cows’ milk and why are they important?

Cow’s milk is a very good source of protein (around 9% by weight), which is important for health at any age, and particularly to support healthy growth and development in infancy and childhood.

Casein and whey are the two main forms of protein in cow’s milk.  Casein is around 4/5 of the total protein in cow’s milk, and whey makes up the rest.1

Proteins are vital to the structure of all our body’s tissues. They also help to create and regulate chemical reactions, and act as messengers, so that our cells, tissues and organs can function normally. 

This is why dietary protein is important at any age for both physical and mental health, but particularly for growing babies and young children.

Unlike many plant-derived proteins, the milk proteins casein and whey both contain all the essential amino acids (building blocks of protein) that we need but can’t make for ourselves.

These milk proteins - and substances we make from them - also have benefits for heart health, energy metabolism, dental health and immune regulation, including prevention of some cancers.1–3

These positive effects of the proteins in cow’s milk, along with the vitamins and essential minerals that it contains (particularly calcium, but also iodine, for which milk is a major dietary source) explain why milk is recommended as part of any healthy diet.4 

Individuals who exclude milk and dairy products from their diets – including vegans and/or individuals with allergies and intolerances therefore need to make sure that their diet is carefully planned and/or supplemented to include adequate intakes of all the essential nutrients that milk and dairy products would provide.

 

2)    What is A2 milk protein?

A2 milk protein refers to a particular form of ‘beta-casein’, one of the major casein proteins found in cow’s milk.

Milk from individual cows may contain the A2 form of the beta-casein protein only, or a slightly different form of beta-casein known as A1 milk protein only, or a combination of the two. 

  • This means that standard cow’s milk in the UK, US and most other developed countries provides a mixture of both A1 and A2 milk protein.5–8

Proteins are made of long chains of different amino acids linked together, which can fold and twist into complex 3-dimensional shapes, allowing them to carry out their many different roles in the body and brain.

When consumed in food and digested, proteins are broken down into shorter chains (called peptides) or to individual amino acids, which can then be used up or re-assembled into new proteins as needed.

The beta-casein protein found in cows’ milk contains 209 amino acids, and very slight differences in these are found in milk from different cows.  

  • Just one different amino acid (at position 67) is used to distinguish A2 from A1-type milk proteins.5–9

A2 protein is the form of beta-casein found in human breastmilk,8,10 and also in some – but not all – cow’s milk.5–9


3)   
Where does A2 protein milk come from?

Human breastmilk contains an A2-type form of beta-casein.8,10,11  Similarly, A2 is also the main form of the beta-casein protein in all other animal milks except for standard cows’ milk - including goat’s and sheep’s milk (as well as milk from donkeys, camels, native buffalo etc).8,12,13

A2 protein milk can also be obtained from cows with a particular genetic ancestry – because this is what determines whether their milk contains A2 protein, A1 protein, or a combination of the two.5–9

Native cattle in many parts of Asia and Africa produce milk that contains only A2 protein. Some other breeds, such as Guernsey cows, produce mainly A2 protein milk.  But most breeds have more varied ancestry, so the proportions of A1 and A2 protein in their milk will differ between cows.5–9  

  • This means that cow’s milk from mainstream dairy herds in the UK and Europe, the USA, Australia and New Zealand contains a mixture of both the A1 and A2 protein forms.

However, simple genetic testing can identify those cows whose milk contains only the A2 form of beta-casein – so in some countries, ‘A2 cows’ milk’ is available, derived from dairy herds made up exclusively of cows selected for producing only A2 beta-casein in their milk (by simple non-invasive genetic testing).

 

4) What makes A2 protein milk different?

The differences between A2 protein milk and ordinary cows’ milk (which also contains A1 protein) follow from what happens during their digestion.14 

The tiny structural difference in the A2 protein means that during digestion, this form of beta-casein breaks down differently from the A1 form. 

This leads to formation of a different balance of protein fragments called peptides: short chains of amino acids with biological effects.14–17

Many of the benefits associated with consuming milk proteins - for heart health, energy metabolism, immune regulation and cancer prevention among others – come from the actions of different peptides that are released when milk proteins are broken down.1,2,18,19

Some evidence indicates that consuming milk containing A2 protein only may reduce the digestive discomfort that some people experience after consuming standard cow’s milk.20–22

This is thought to be because some of the peptides created by the digestion of A2 beta-casein are less likely to trigger ‘intolerance’ reactions in vulnerable individuals than those released when A1 beta-casein is digested.

Very importantly, intolerance reactions to milk are not the same as milk allergy (which can be identified via medical tests).

Individuals with a classic cow’s milk allergy need to avoid all dairy products -including A2 versions - and follow professional advice to ensure their diet provides all the nutrients and energy they need.

 

6) Are there any benefits of drinking A2 protein milk?

There are good scientific reasons why drinking A2 protein milk may have benefits for some people,7,23–25 but most evidence for this comes from experimental or animal studies,26,27,36–38,28–35 or from general population studies that are purely observational,39,40 and so can’t establish cause-and effect.8 

For clear evidence of causal effects, human clinical trials (involving random allocation, placebo-control, and double-blinding) are needed.  

There are a few such trials of A2 protein milk – but only in adults, and mainly for digestive symptoms indicating milk intolerance.25

In two clinical trials, Chinese adults with intolerance to lactose (the sugar in milk) showed significantly fewer digestive symptoms when drinking A2 protein milk versus standard cow’s milk.21,22  Their attention and memory performance (as measured via computerised tests) was also better when consuming A2 protein milk compared with standard cows’ milk.21

Another randomised controlled trial found that in US adults, drinking A2 protein milk led to higher blood levels of a key antioxidant enzyme (glutathione), but other measures of health or wellbeing weren’t included.41

  • More research is still needed to confirm other possible benefits of A2 protein for health and wellbeing – and any such benefits may only apply for particular individuals or subgroups who have higher-than-average risks for digestive, immune or other health issues.

Meanwhile, one important potential benefit of A2 protein milk can be in allowing individuals who would otherwise avoid milk to include this highly nutritious food in their diets.4

Anecdotal reports suggest possible benefits for some children and adults from consuming A2 protein milk rather than standard cows’ milk – typically for digestive symptoms (particularly constipation) - but also ‘chronic stuffy nose’, wheeze or bronchitis, eczema; and difficulties with memory, attention and concentration (often called ‘brain fog’).

There is a plausible scientific rationale (involving complex links between the gut, brain and immune system) for why A2 protein milk could make such positive differences for some people.7,26,35–38,27–34

However, more research is still needed to find out exactly which individuals or subgroups of the population may derive any health benefits from consuming milk that contains the A2 form of the beta-casein protein only, compared with standard cows’ milk (containing both A1 and A2 beta-casein).

References

1.          Davoodi SH, Shahbazi R, Esmaeili S, et al. Health-related aspects of milk proteins. Iran J Pharm Res. 2016;15(3):573-591. doi:10.22037/ijpr.2016.1897

2.          Ma F, Wei J, Hao L, et al. Bioactive Proteins and their Physiological Functions in Milk. Curr Protein Pept Sci. 2019;20(7):759-765. doi:10.2174/1389203720666190125104532

3.          Shah NP. Effects of milk-derived bioactives: an overview. Br J Nutr. 2000;84 Suppl 1:S3-10. Accessed May 22, 2017. http://www.ncbi.nlm.nih.gov/pubmed/11242440

4.          Marangoni F, Pellegrino L, Verduci E, et al. Cow’s Milk Consumption and Health: A Health Professional’s Guide. J Am Coll Nutr. 2019;38(3):197-208. doi:10.1080/07315724.2018.1491016

5.          Caroli AM, Chessa S, Erhardt GJ. Invited review: milk protein polymorphisms in cattle: effect on animal breeding and human nutrition. J Dairy Sci. 2009;92(11):5335-5352. doi:10.3168/jds.2009-2461

6.          Ng-Kwai-Hang K, Grosclaude F. Genetic Polymorphism of Milk Proteins. In: Fox P, McSweeney P, eds. Advanced Dairy Chemistry. Kluwer Academic / Plenum Publishers; 2002:737-814.

7.          Kamiński S, Cieślińska A, Kostyra E. Polymorphism of bovine beta-casein and its potential effect on human health. J Appl Genet. 2007;48(3):189-198. doi:10.1007/BF03195213

8.          De Noni I, FitzGerald R, Hannu J, et al. Review of the potential health impact of β-casomorphins and related peptides. EFSA J. 2009;7(2):231r. doi:10.2903/j.efsa.2009.231r

9.          Raynes JK, Day L, Augustin MA, Carver JA. Structural differences between bovine A1 and A2 β-casein alter micelle self-assembly and influence molecular chaperone activity. J Dairy Sci. 2015;98(4):2172-2182. doi:10.3168/jds.2014-8800

10.        Steinerová A, Racek J, Rajdl D, et al. Letter to the Editor. Atherosclerosis. 2004;173(1):147-148. doi:10.1016/j.atherosclerosis.2003.12.006

11.        Wada Y, Lönnerdal B. Bioactive peptides released from in vitro digestion of human milk with or without pasteurization. Pediatr Res. 2015;77(4):546-553. doi:10.1038/pr.2015.10

12.        Selvaggi M, Laudadio V, Dario C, Tufarelli V. Major proteins in goat milk: An updated overview on genetic variability. Mol Biol Rep. 2014;41(2):1035-1048. doi:10.1007/s11033-013-2949-9

13.        Selvaggi M, Laudadio V, Dario C, Tufarelli V. Investigating the genetic polymorphism of sheep milk proteins: A useful tool for dairy production. J Sci Food Agric. 2014;94(15):3090-3099. doi:10.1002/jsfa.6750

14.        Noni I De. Release of β-casomorphins 5 and 7 during simulated gastro-intestinal digestion of bovine β-casein variants and milk-based infant formulas. Food Chem. 2008;110(4):897-903. doi:10.1016/j.foodchem.2008.02.077

15.        Ul Haq MR, Kapila R, Kapila S. Release of β-casomorphin-7/5 during simulated gastrointestinal digestion of milk β-casein variants from Indian crossbred cattle (Karan Fries). Food Chem. 2015;168:70-79. doi:10.1016/j.foodchem.2014.07.024

16.        Asledottir T, Le T, Petrat-Melin B, Devold T, Larsen L, Vegararud G. Identification of Bioactive peptides and quantification of Beta-Casomorphin-7 from Bovine Beta-Casein A1,A2 and I after Ex Vivo Gastrointestinal Digestion. Int Dairy J. 2017;In Press.

17.        Cieślińska A, Kostyra E, Kostyra H, Oleński K, Fiedorowicz E, Kamiński S. Milk from cows of different β-casein genotypes as a source of β-casomorphin-7. Int J Food Sci Nutr. 2012;63(4):426-430. doi:10.3109/09637486.2011.634785

18.        Wada Y, Lönnerdal B. Bioactive peptides derived from human milk proteins — mechanisms of action. J Nutr Biochem. 2014;25(5):503-514. doi:10.1016/j.jnutbio.2013.10.012

19.        Ul Haq MR, Ul Haq MR. Significant Food-Derived Opioid Peptides. In: Opioid Food Peptides. Springer Singapore; 2020:1-20. doi:10.1007/978-981-15-6102-3_1

20.        Pal S, Woodford K, Kukuljan S, Ho S. Milk Intolerance, Beta-Casein and Lactose. Nutrients. 2015;7(9):7285-7297. doi:10.3390/nu7095339

21.        Jianqin S, Leiming X, Lu X, Yelland GW, Ni J, Clarke AJ. 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;15(1):35. doi:10.1186/s12937-016-0147-z

22.        He M, Sun J, Jiang ZQ, Yang YX. Effects of cow’s milk beta-casein variants on symptoms of milk intolerance in Chinese adults: a multicentre, randomised controlled study. Nutr J. 2017;16(1):72. doi:10.1186/s12937-017-0275-0

23.        Ul Haq MR, Kapila R, Shandilya UK, Kapila S. Impact of milk-derived β-casomorphins on physiological functions and trends in research: a review. Int J Food Prop. 2014;17:1726-1741. https://sireiki.co.uk/wp-content/uploads/2016/07/document.pdf

24.        Bell SJ, Grochoski GT, Clarke AJ. Health Implications of Milk Containing β-Casein with the A2 Genetic Variant. Crit Rev Food Sci Nutr. 2006;46(1):93-100. doi:10.1080/10408390591001144

25.        Brooke-Taylor S, Dwyer K, Woodford K, Kost N. Systematic Review of the Gastrointestinal Effects of A1 Compared with A2 β-Casein. Adv Nutr An Int Rev J. 2017;8(5):739-748. doi:10.3945/an.116.013953

26.        Ul Haq MR, Kapila R, Sharma R, Saliganti V, Kapila S. Comparative evaluation of cow β-casein variants (A1/A2) consumption on Th2-mediated inflammatory response in mouse gut. Eur J Nutr. 2014;53(4):1039-1049. doi:10.1007/s00394-013-0606-7

27.        Trivedi MS, Shah JS, Al-Mughairy S, et al. Food-derived opioid peptides inhibit cysteine uptake with redox and epigenetic consequences. J Nutr Biochem. 2014;25(10):1011-1018. doi:10.1016/j.jnutbio.2014.05.004

28.        Trivedi MS, Hodgson NW, Walker SJ, Trooskens G, Nair V, Deth RC. Epigenetic effects of casein-derived opioid peptides in SH-SY5Y human neuroblastoma cells. Nutr Metab (Lond). 2015;12(1):54. doi:10.1186/s12986-015-0050-1

29.        Trivedi M, Zhang Y, Lopez-Toledano M, Clarke A, Deth R. Differential neurogenic effects of casein-derived opioid peptides on neuronal stem cells: implications for redox-based epigenetic changes. J Nutr Biochem. 2016;37:39-46. doi:10.1016/j.jnutbio.2015.10.012

30.        Barnett MPG, McNabb WC, Roy NC, Woodford KB, Clarke AJ. Dietary A1 β -casein affects gastrointestinal transit time, dipeptidyl peptidase-4 activity, and inflammatory status relative to A2 β -casein in Wistar rats. Int J Food Sci Nutr. 2014;65(6):720-727. doi:10.3109/09637486.2014.898260

31.        Wasilewska J, Sienkiewicz-Szłapka E, Kuźbida E, Jarmołowska B, Kaczmarski M, Kostyra E. The exogenous opioid peptides and DPPIV serum activity in infants with apnoea expressed as apparent life threatening events (ALTE). Neuropeptides. 2011;45(3):189-195. doi:10.1016/j.npep.2011.01.005

32.        Fiedorowicz E, Kaczmarski M, Cieślińska A, et al. β-casomorphin-7 alters μ-opioid receptor and dipeptidyl peptidase IV genes expression in children with atopic dermatitis. Peptides. 2014;62:144-149. doi:10.1016/j.peptides.2014.09.020

33.        Kost N V, Sokolov OY, Kurasova OB, et al. Beta-casomorphins-7 in infants on different type of feeding and different levels of psychomotor development. Peptides. 2009;30(10):1854-1860. doi:10.1016/j.peptides.2009.06.025

34.        Sokolov O, Kost N, Andreeva O, et al. Autistic children display elevated urine levels of bovine casomorphin-7 immunoreactivity. Peptides. 2014;56:68-71. doi:10.1016/j.peptides.2014.03.007

35.        Trompette A, Claustre J, Caillon F, Jourdan G, Chayvialle JA, Plaisancié P. Milk bioactive peptides and beta-casomorphins induce mucus release in rat jejunum. J Nutr. 2003;133(11):3499-3503. Accessed April 4, 2017. http://www.ncbi.nlm.nih.gov/pubmed/14608064

36.        Martínez-Maqueda D, Miralles B, De Pascual-Teresa S, Reverón I, Muñoz R, Recio I. Food-Derived Peptides Stimulate Mucin Secretion and Gene Expression in Intestinal Cells. J Agric Food Chem. 2012;60(35):8600-8605. doi:10.1021/jf301279k

37.        Sun Z, Zhang Z, Wang X, Cade R, Elmir Z, Fregly M. Relation of beta-casomorphin to apnea in sudden infant death syndrome. Peptides. 2003;24(6):937-943. Accessed March 18, 2017. http://www.ncbi.nlm.nih.gov/pubmed/12948848

38.        Jarmołowska B, Bukało M, Fiedorowicz E, et al. Role of Milk-Derived Opioid Peptides and Proline Dipeptidyl Peptidase-4 in Autism Spectrum Disorders. Nutrients. 2019;11(1):87. doi:10.3390/nu11010087

39.        Laugesen M, Elliott R. Ischaemic heart disease, Type 1 diabetes, and cow milk A1 beta-casein. N Z Med J. 2003;116(1168):U295. Accessed March 19, 2017. http://www.ncbi.nlm.nih.gov/pubmed/12601419

40.        Chia JSJ, McRae JL, Kukuljan S, et al. A1 beta-casein milk protein and other environmental pre-disposing factors for type 1 diabetes. Nutr Diabetes. 2017;7(5):e274. doi:10.1038/nutd.2017.16

41.        Deth R, Clarke A, Ni J, Trivedi M. Clinical evaluation of glutathione concentrations after consumption of milk containing different subtypes of β-casein: results from a randomized, cross-over clinical trial. Nutr J. 2016;15(1):82. doi:10.1186/s12937-016-0201-x