Milk Intolerance and Inflammation May be Caused by A1 Beta-Casein

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 only 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, camel 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 passed on to other northern European breeds of cows, including Friesian, Ayrshire and British Shorthorn since Holsteins were bred with them 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 and 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 Difference Between A1 and A2 Beta-Casein

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 in 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 drank  250 mL of either A1/A2 or A2 milk following each of two meals over a 14-day period. 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 that drank A2 milk [7].

Addendum (July 22, 2019): *there has been some anecdotal evidence that people with arthritis do considerably better when they do not consume casein (see Arthritis Foundation website).

In a large scale 2017 randomized cross-over design follow-up study, 600 adult who reported lactose intolerance and digestive discomfort following milk consumption were assigned over a 7-day period to consume either 300 mL of conventional milk containing both A1 and A2 beta casein, or only A2 milk. Results indicated 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.

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” does not apply to the milk and cheese available to them.

Final Thoughts…

While much research has yet to be done to determine the extent that A1 beta-casein proteins impact human health, those with suspected lactose intolerance who continue to have symptoms while consuming lactose-free milk and low-lactose products such as yogurt and hard cheese, should try eliminating milk produced at ordinary large-scale dairies that have milk containing both A1 and A2 beta-casein to see if their symptoms improve.  As a substitute, they could use goat milk or buffalo milk, or find small, local dairies that use “heritage herd” cows, such as specific species of Jerseys, Guernseys, Brown Swiss, and Normandes that only produce milk with A2 beta-casein.

Note: My tried and true recipe for making homemade goat or A2 yogurt in an oven or crock-pot using a temperature controller, as well as turning it into thick Greek yogurt is posted here.

Those with histamine-intolerance in the US, Canada and Australia might feel better avoiding milk, cheese, and yogurt from conventional dairies, as these contain A1 beta-casein, which are high histamine liberators. After a period of dairy avoidance to enable mast cells to calm, dairy products from “heritage herd” cows can then be trialed.

NOTE: Butter and full-fat (whipping) cream are entirely fat, and as such do not contain either A1 or A2 beta-casein proteins. These would be fine to consume regardless of which dairy they were from.

More Info?

If you have food allergies or food intolerances, including what you thought was lactose intolerance, or have been diagnosed with histamine-intolerance or Mast-Cell Activation Disorder (MCAD), I can help.

You can find out more about the packages and hourly consultations I offer under the Services tab or by clicking here. If you would like further information, please send me a note using the Contact Me form above and I will reply as soon as I can.

To your good health!

Joy

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References

  1. Ware M, Metropulos M, Medical News Today, A2 milk: What you need to know, July 25, 2017, https://www.medicalnewstoday.com/articles/318577.php
  2. Pasin G. A2 milk facts. California Dairy Research Foundation website. http://cdrf.org/2017/02/09/a2-milk-facts/. Published February 9, 2017.
  3.  European Food Safety Authority. Review of the potential health impact of β-casomorphins and related peptides. EFSA J. 2009;7(2):1-107.
  4. Kurek M, Przybilla B, Hermann K, A naturally occurring opioid peptide from cow’s milk, beta-casomorphine-7, is a direct histamine releaser in man, Int Arch Allergy Immunol. 1992;97(2):115-20.
  5. Pal S, Woodford K, Kukuljan S, Ho S. Milk intolerance, beta-casein and lactose. Nutrients. 2015;7(9):7285-7297.
  6.  Ho S, Woodford K, Kukuljan S, Pal S. Comparative effects of A1 versus A2 beta-casein on gastrointestinal measures: a blinded randomised cross-over pilot study. Eur J Clin Nutr. 2014;68(9):994-1000.
  7. 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;15:35
  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: a multicentre, randomised controlled study. Nutr J. 2017 Oct 25;16(1):72.
  9. Molderings GJ, Brettner S, Homann J, Afrin LB. Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options. J Hematol Oncol. 2011;4:10. Published 2011 Mar 22. doi:10.1186/1756-8722-4-10
  10. Lamprecht H, Swiss Interest Group Histamine Intolerance (SIGHI), Histamine Intolerance Food Compatibility List, wwww.mastzellaktivierung.info & www.histaminintoleranz.ch

This article is based in part on material by Judith C. Thalheimer, RD, LDN, Is A2 Milk the Game-Changer for Dairy Intolerance?Today’s Dietitian, Vol. 19, No. 10, P. 26

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