Milk Intolerance May be Caused by A1 Beta-Casein

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NOTE: This article was written and posted on July 21, 2019, and was completely updated and expanded on December 29, 2025.

Introduction

Digestive issues that result from milk consumption are often attributed to lactose intolerance, but research indicates that it may be the result of an intolerance to a specific type of protein found in some types of cow’s milk; specifically A1 beta-casein.

Casein and whey are the two primary proteins found in milk, with casein accounting for ~ 80 % of the protein in milk. Approximately 30% of the protein in milk is beta-casein.

There are two variants of beta-casein: A1 and A2; however, before cows were domesticated, they only produced milk that contained the A2 form of beta-casein[1,2]. Older breeds of cows, such as most Jerseys, Guernseys, Brown Swiss, Normandes, as well as most of the cows in Asia, Africa, and southern Europe[2], produce milk with the A2 variant of beta-casein, as do goats, sheep, donkeys, yaks, camels, and buffalo [2]. In addition, human milk contains A2 beta-casein.

It is thought that ~8,000 years ago, a single-gene mutation occurred in Holsteins, which resulted in the production of the A1 beta-casein protein in this breed. This novel gene variant was subsequently inherited by other northern European cattle breeds, including Friesian, Ayrshire, and British Shorthorn, as Holsteins were bred with these breeds to improve milk production [2]. 

Today’s Holstein breed is the most common dairy cow in the US, Canada, Australia, and northern Europe and carries both A1 and A2 forms of beta-casein in approximately equal amounts [2].

Milk intolerance may not always be due to lactose intolerance, but due to intolerance to milk containing A1 beta-casein.

Note: Primary lactose intolerance is a result of a lack of the enzyme lactase, which is genetic in origin. This is a permanent condition. Secondary lactose intolerance is temporary and the result of being sick with something that causes diarrhea, which sloughs off the lactase from the wall of the intestine. Genuine lactose intolerance can be tested with a hydrogen breath test.

Research suggests that A1 beta-casein protein may be at the root of stomach pain and other gastrointestinal (GI) symptoms associated with consumption of milk from A1 cows, which closely resemble lactose intolerance. These symptoms are not present when consuming milk from cows that only produce A2 beta-casein. Food-derived peptides such as β-casomorphins and others are known to have different effects on the intestines, including the secretions of the stomach and pancreas, as well as gut motility [3]. Studies have found that a peptide called β-(beta) casomorphin (BCM-7) may be behind stomach pain and other symptoms associated with milk containing A1 beta-casein.

The History of A1 and A2 Beta-Casein

Casein makes up approximately 80% of the protein in milk, and beta-casein accounts for about 30% of that total. Originally, all domesticated cows produced milk containing only the A2 variant of beta-casein. This is the same variant found in human breast milk, as well as milk from goats, sheep, and buffalo. Approximately 8,000 years ago, a genetic mutation occurred in Holsteins, leading to the production of the A1 protein. Today, Holsteins are the primary dairy breed in North America and Northern Europe, meaning most commercially available milk contains a mixture of both A1 and A2 proteins.

If one thinks of proteins as chains of amino acids strung together like train cars in a train, each one of the ‘cars’ represents a different amino acid.  In the older A2 beta-casein variant, the ‘car’ which occupies the 67th position is an amino acid called proline, but in the newer A1 beta-casein variant, the amino acid in the 67th position is histidine. When milk with A1 beta-casein is digested, the histidine bond breaks, resulting is a peptide made up of 7 amino acids, called β-(beta) casomorphin-7 (BCM-7).

β-(beta) casomorphin-7 (BCM-7) is a naturally occurring opioid peptide with a structure similar to morphine and is known to bind to opioid receptors [3]. What effect does BCM-7 have on the body as a result of binding with these opioid receptors?

A 2015 review paper cites research demonstrating that milk containing A1 beta-casein increases GI transit time (the amount of time that it takes for food to go through the GI tract), which means it slows it down, and in animal studies, increases inflammatory markers significantly more than A2 beta-casein-containing milk[5]. In a small, double-blinded, randomized crossover study from 2014 with 41 subjects, it was found that participants consuming A1 beta-casein cow’s milk had significantly softer stools, more bloating, and more abdominal pain than those drinking A2 beta-casein milk [6]. In another unrelated double-blind, randomized, crossover trial from 2016 with 45 Chinese participants with self-reported intolerance to cow’s milk, participants drank  250 mL of either A1/A2 or A2 milk following each of two meals over 14 days. When drinking the A1 beta-casein milk, there was an increase in transit time and in GI inflammation, and a worsening of digestive discomfort [7] as well as an increase in inflammatory markers such as IgG, IgE, and IgG1. These were significantly lower in those who drank A2 milk [7].

In a large-scale 2017 randomized crossover design follow-up study, 600 adults who reported lactose intolerance and digestive discomfort following milk consumption were assigned over 7 days to consume either 300 mL of conventional milk containing both A1 and A2 beta casein, or only A2 milk. Results indicated that digestive symptoms were markedly reduced after consuming A2 milk versus conventional milk [8].

Healthcare professionals have often assumed (without giving people hydrogen breath tests to confirm it) that people with GI symptoms related to consuming dairy products have lactose intolerance, when it is possible that the symptoms could be related to intolerance of A1 beta-casein.

Why A1 Milk Causes Inflammation

The difference between A1 and A2 beta-casein comes down to a single amino acid at the 67th position of the protein chain. In A2 milk, this position is held by proline. In A1 milk, it is held by histidine. When A1 milk is digested, this histidine bond breaks, creating a peptide called beta-casomorphin-7 (BCM-7). BCM-7 is an opioid peptide that can slow down gastrointestinal transit time and increase inflammatory markers, leading to symptoms that mimic lactose intolerance, such as bloating and abdominal pain.

The “Trifecta” Connection: MCAS, POTS, and EDS

Concerning to those with histamine-intolerance, including those with Mast Cell Activation Disorder (MCAD) who need to lower their intake of histadine-containing foods and histamine-liberators [9] may unknowingly be adversely affected by milk commonly available in the US, Canada, Australia, and northern Europe that contains A1 beta-casein, as when it is digested it produces betacasomorphin-7 (BCM-7), a potent histamine liberator. The most well-known Histamine Intolerance Food Compatibility List from the Swiss Histamine Intolerance Group (SIGHI) lists milk as producing a low reaction — perhaps because the milk available in Central Europe, as in southern Europe, contains A2 beta casein, and not A1 beta-casein as in North America, Australia, and northern Europe [10]. Those with histamine-intolerance in the US and Canada, for example, and other countries with A1 beta-casein in dairy need to be aware that the milk and the hard cheeses listed as being “well-tolerated, no symptoms expected at usual intake” do not apply to the milk and cheese available to them.

For patients managing the “Trifecta” of Mast Cell Activation Syndrome (MCAS), Postural Orthostatic Tachycardia Syndrome (POTS), and Ehlers-Danlos Syndrome (EDS), the choice of dairy is a critical clinical intervention rather than a minor dietary preference [11,12,13].

Practical Steps for Relief

If you suspect a sensitivity to A1 proteins, consider switching to A2-only sources. This includes goat’s milk, sheep’s milk, or milk from specific “heritage” cow breeds like Jerseys or Guernseys. It is also worth noting that butter and full-fat whipping cream are almost entirely fat and do not contain significant amounts of casein, meaning they are generally well-tolerated regardless of the source. For many, switching to A2 dairy allows them to enjoy milk products again without inflammation or GI upset.

More Info?

I used to offer a Food Allergy/Food Sensitivity Package; however, most people would be seeking services based on IgG Food Sensitivity tests purchased through a naturpath. rather than IgE-mediated test results obtained through an allergist.  I continue to support those diagnosed with IgE-mediated food allergies and, depending on the severity, will usually do so within the context of add-on services to the Comprehensive Dietary Package. You can learn about me here.

To your good health!

Joy

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References

  1. Ware M. A2 milk: What you need to know. Medical News Today. 2017. [https://www.medicalnewstoday.com/articles/318577.php]
  2. Pasin G. A2 milk facts. California Dairy Research Foundation. 2017. [http://cdrf.org/2017/02/09/a2-milk-facts/]
  3. European Food Safety Authority. Review of the potential health impact of β-casomorphins and related peptides. EFSA Journal. 2009. [https://doi.org/10.2903/j.efsa.2009.231r]
  4. Kurek M, Przybilla B, Hermann K, et al. A naturally occurring opioid peptide from cow’s milk, beta-casomorphine-7, is a direct histamine releaser in man. International Archives of Allergy and Immunology. 1992;97(2):115-20. [https://doi.org/10.1159/000236106]
  5. Pal S, Woodford K, Kukuljan S, et al. Milk intolerance, beta-casein and lactose. Nutrients. 2015;7(9):7285-97. [https://doi.org/10.3390/nu7095339]
  6. Ho S, Woodford K, Kukuljan S, et al. Comparative effects of A1 versus A2 beta-casein on gastrointestinal measures. European Journal of Clinical Nutrition. 2014;68(9):994-1000. [https://doi.org/10.1038/ejcn.2014.127]
  7. Jianqin S, et al. Effects of milk containing only A2 beta casein versus milk containing both A1 and A2 beta casein proteins on gastrointestinal physiology. Nutrition Journal. 2016;15:35. [https://doi.org/10.1186/s12937-016-0147-z]
  8. He M, Sun J, Jiang ZQ, et al. Effects of cow’s milk beta-casein variants on symptoms of milk intolerance in Chinese adults. Nutrition Journal. 2017;16(1):72. [https://doi.org/10.1186/s12937-017-0275-0]
  9. Molderings GJ, et al. Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options. Journal of Hematology & Oncology. 2011;4:10. [https://doi.org/10.1186/1756-8722-4-10]
  10. Swiss Interest Group Histamine Intolerance (SIGHI). Histamine Intolerance Food Compatibility List. [https://www.mastzellaktivierung.info]
  11. Stepnik M, & Kurek M. (2002). The influence of bovine casein-derived exorphins on mast cells in rodents. ResearchGate. [https://www.researchgate.net/publication/223521751]
  12. POTS UK. (2025). Mast Cell Activation Syndrome – Associated Conditions. [https://www.potsuk.org/about-pots/associated-conditions/mcas/]
  13. The EDS Clinic. (2025). POTS and MCAS: What is the link? [https://www.eds.clinic/articles/mast-cell-activation-syndrome-postural-orthostatic-tachycardia-syndrome]
 
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