Cow’s milk contains a number of different proteins, one of which is beta-casein. There are several different genetic variants of this protein, the most common being A1 and A2. Different individual cattle and cattle breeds differ with respect to which beta-casein variant is present in the milk. A1 beta-casein and A2 beta-casein are present in differing ratios in the milk supply of different countries. In the United States, 40% of the beta-casein is the A1 variant. The corresponding figures for the United Kingdom and Australia are 53% and 21%, respectively.

When A1 beta-casein is digested in vitro by intestinal enzymes, it yields a bioactive peptide, beta-casomorphin-7. In contrast, beta-casomorphin-7 is not produced by digestion of the A2 variant. Beta-casomorphin-7 has opioid properties and also alters immune function.

Beta-Casein Variants and Cardiovascular Disease

In an observational study of 20 affluent countries, a significant positive association was found between per capita A1 consumption and ischemic heart disease mortality 5 years later (r = 0.76; p < 0.001). No such association was found between A2 consumption and ischemic heart disease mortality.¹ In rabbits with experimentally induced atherosclerosis, the severity of the atherosclerosis was significantly greater when the diet contained A1 than when it contained A2.²

Beta-Casein Variants and Type 1 Diabetes

Non-obese mice (an animal model for type 1 diabetes) developed type 1 diabetes when fed A1, but not when fed A2. However, non-obese diabetic mice did not develop diabetes when A1 was given with naloxone, a drug that antagonizes the opioid effect of betacasomorphin-7. In a study conducted in affluent countries, a significant positive association was found between national per capita consumption of A1 protein and incidence of type 1 diabetes. In contrast, no significant association was found with total milk protein consumption or with consumption of A2 or other variants of beta-casein.³

Beta-Casein Variants and Gastrointestinal Symptoms

Eighty Chinese children (aged 5-6 years) who experienced mild-to-moderate gastrointestinal symptoms after drinking milk and who were not regular milk drinkers were randomly assigned to consume, in double-blind fashion, conventional milk (150 ml twice a day for 5 days) or the same amount of milk that contained only A2 beta-casein. After a nine-day washout period, each child consumed the other type of milk for an additional five days. Mean severity of gastrointestinal symptoms (as determined by a visual analog scale) was significantly less with A2 milk than with conventional milk. Serum levels of inflammatory markers were significantly higher with conventional milk than with A2 milk.⁴

In another study, 40 New Zealand women (mean age, 25 years) with self-reported intolerance to dairy products underwent a 50-g lactose challenge. Participants were classified as lactose intolerant if they developed symptoms after ingestion of lactose and also showed evidence of lactose malabsorption. They were classified as non-lactose dairy intolerant if considerable symptoms occurred after ingestion of dairy products, whereas lactose ingestion caused minimal symptoms and lactose absorption was relatively normal. All participants underwent double-blind challenges with 750 ml of three different types of milk on three separate days, in random order: 1) conventional milk (containing lactose and both A1 and A2 beta-casein), 2) A2 milk (containing lactose and only A2 beta-casein), and 3) lactose-free conventional milk (containing both A1 and A2 beta-casein).

Among lactose-intolerant subjects, compared with conventional milk, A2 milk significantly decreased post-challenge nausea and fecal urgency, and significantly attenuated the rise in breath hydrogen concentration over a 3-hour period. In contrast, non-lactose dairy intolerant subjects experienced symptoms such as abdominal distension, bloating, and flatulence (and no increase in breath hydrogen concentration) irrespective of the type of milk consumed.⁵ These findings indicate that, among lactose-intolerant individuals, digestive symptoms and lactose malabsorption was significantly decreased if the milk contained exclusively A2 beta-casein. The results are consistent with other research suggesting that symptoms of lactose intolerance are due in part to beta-casomorphin-7.

Implications of the Research

The results of these studies suggest that A2 milk may be safer than conventional milk for people who are at risk of developing cardiovascular disease or type 1 diabetes. In addition, A2 milk, as compared with conventional milk, causes fewer gastrointestinal symptoms in lactose-intolerant individuals. However, lactose-free milk (which is widely available) would be preferable to A2 milk for people with lactose intolerance. A2 milk is now available in many food stores in the US.

Information about the type of beta-casein present in various milk products is not readily available, but “A2 milk” is now available in the US.

References

1. Laugesen M, Elliott R. Ischaemic heart disease, type 1 diabetes, and cow milk A1   beta-casein. N Z Med J. 2003;116(1168):U295.
2. Tailford KA, et al. A casein variant in cow’s milk is atherogenic. Atherosclerosis. 2003;170:13-19.
3. Elliott RB, et al. Type I (insulin-dependent) diabetes mellitus and cow milk: casein variant consumption. Diabetologia. 1999;42:292-296.
4. Sheng X, et al. Effects of conventional milk versus milk containing only A2 beta-casein on digestion in Chinese children: a randomized study. J Pediatr Gastroenterol Nutr. 2019;69:375-382.
5. Milan AM, et al. Comparison of the impact of bovine milk beta-casein variants on digestive comfort in females self-reporting dairy intolerance: a randomized controlled trial. Am J Clin Nutr. 2020;111:149-160.

Published May 20, 2023