October 2017 Issue

Is A2 Milk the Game-Changer for Dairy Intolerance?
By Judith C. Thalheimer, RD, LDN
Today's Dietitian
Vol. 19, No. 10, P. 26

Research suggests the milk protein beta-casein and not the milk sugar lactose may be causing much of the GI distress linked with dairy milk consumption.

If consuming dairy causes digestive issues, is it lactose intolerance? Or could it be protein intolerance? Research suggests that a common form of cow's milk beta-casein protein (called A1) could potentially cause stomach pain and other gastrointestinal (GI) symptoms. Another variant of the protein, called A2, isn't associated with these adverse effects.

If some people who believe they're lactose intolerant are actually reacting to A1 beta-casein, then drinking milk from cows with only the gene for the A2 variant could relieve their digestive issues. As milk with only A2 beta-casein protein is rolled out in the US marketplace, dietitians must be ready to answer questions from clients about the potential health benefits of this product and address any fears raised by suggestions of a negative health impact of traditional A1-containing dairy products.

Dairy-Ache
Babies are born with the ability to produce the enzyme lactase, which breaks down the milk sugar lactose. But approximately 65% of the human population has a reduced ability to produce lactase after infancy.1 Lactose intolerance is less common if dairy has been an important part of a population's diet for generations. For example, people of Northern European descent, for whom dairy is traditionally a dietary staple, can have rates of lactose intolerance as low as 5%. But in some communities of East Asian descent, where consumption of dairy products historically hasn't been common, rates can be as high as 90%.1 Individuals with lactose intolerance may experience abdominal pain, bloating, flatulence, nausea, and diarrhea beginning 30 minutes to two hours after consuming lactose-containing dairy products.1

It's been suggested that, in some individuals, these symptoms could be caused not by lactose but by a byproduct of digestion of a natural variant in the beta-casein protein. Casein accounts for approximately 82% of the proteins in cow's milk. Of these, beta-casein is the second most common.2

Thousands of years ago, a single-gene mutation in Holstein cows changed the expression of the beta-casein protein. As Holsteins were crossed with other breeds, the mutation spread. There now are 12 variants of the beta-casein gene, of which A1 and the original, A2, are the most common.2 According to the California Dairy Research Foundation, the typical dairy cow in the United States produces approximately equal amounts of A1 and A2 forms of beta-casein in its milk. Dairy herds in much of Asia and Africa and parts of Southern Europe are naturally more likely to produce only A2 proteins.2

The difference between A1 and A2 beta-casein proteins is just one amino acid: A1 has the amino acid histidine at position 67 in the chain, while A2 instead has proline in that position.3 But that one amino acid apparently changes how the protein is cleaved during digestion. The enzymatic hydrolysis of A1 beta-casein, but not A2, produces a peptide called beta-casomorphin, or BCM-7.3

Food-derived peptides are known to have different effects on the intestines, including affecting motility and gastric and pancreatic secretions.4 Studies have claimed that BCM-7 has inflammatory actions that can cause stomach pain and other symptoms.3 A 2015 review cites studies showing that milk containing A1 beta-casein increases GI transit time and inflammatory markers in rodents significantly more than milk containing only A2 beta-casein. The authors attribute this association to the action of BCM-7.5

In 2014, a small (41 participants), industry-connected, double-blinded, randomized crossover study in humans showed that participants consuming cow's milk with A1 beta-casein had significantly softer stools and more bloating and abdominal pain than those receiving A2 beta-casein milk. The authors of that study concluded that the results should be considered preliminary but that they do suggest a difference in GI responses.6

Another small, industry-connected study in 2016 reported increased GI inflammation, delayed transit, worsening of postdairy digestive discomfort, and decreased cognitive processing speed and accuracy in the 45 Chinese participants with self-reported intolerance to cow's milk. Symptoms were attenuated by the elimination of A1 beta-casein.7

Results of studies like these are being used to market milk containing only A2 beta-casein. "Milk with A2 beta-casein is being promoted as easier to digest," says Angela Lemond, RDN, CSP, LD, a private practice dietitian and spokesperson for the Academy of Nutrition and Dietetics. "The concept is that, if you think you have digestive issues when consuming dairy products, you might have a protein intolerance, not a lactose intolerance."

Frightening Possibilities
In addition to A1 beta-casein's proposed role in digestive issues, this ubiquitous milk protein has been studied as a contributor to health issues such as heart disease, diabetes, schizophrenia, autism, and sudden infant death syndrome. However, data are lacking, are conflicting, or have been refuted for each of these conditions.4,8,9

Some of these proposed health impacts have been attributed to BCM-7, which is suggested to cause or aggravate inflammatory responses in the body. It also has been suggested that BCM-7 can be immunosuppressive and could potentially affect opioid receptors in the nervous, endocrine, and immune systems.10,11

BCM-7 is a bioactive opioid peptide. Animal studies clearly indicate that it can bind to opioid receptors, although apparently not very strongly.4 Much of the data on the opioid effects of BCM-7 were collected in animal studies in which the peptides were injected into the animal rather than digested. However, to act in the human body, BCM-7 peptides would have to make it through the intestinal epithelium and avoid being broken down in the plasma or the liver. To act on the central nervous system, they also would need to cross the blood-brain barrier.4

In 2003, a correlation study estimated the per capita cow A1 beta-casein intake in 20 countries and compared it with rates of ischemic heart disease mortality and incidence of type 1 diabetes five years later. The study found a significant positive correlation between A1 (but not A2) beta-casein and both conditions. Type 1 diabetes incidence changed 1.3% for every 1% change in A1 protein intake per capita.12 While this study raises concerns for possible negative health effects of milk containing A1 beta-casein, it shows only correlation, not causation, and has been accused of not accounting for confounding factors.3,4

Another study found rabbits fed A1 beta-casein isolate for six weeks had significantly higher serum cholesterol, LDL, HDL, and triglyceride levels than those fed A2 beta-casein.13 However, the experimental model in this study has been called into question, and there are doubts about its extrapolation to humans.4

A report by the European Food Safety Authority (EFSA) looked closely at these studies and others conducted up until 2009 and concluded, "based on the present review of available scientific literature, a cause-effect relationship between the oral intake of BCM-7 or related peptides and etiology or course of any suggested noncommunicable disease cannot be established."4

An online search of scientific literature and analysis of a website that bills itself as a comprehensive resource of published scientific literature on A1 and A2 beta-casein and human health (betacasein.net) found very few human studies and no large trials to shed light on these issues since the publication of the EFSA review in 2009.

Addressing Public Perception
While human studies on the potential negative effects of A1 beta-casein on long-term human health are inconclusive at this time, studies and articles asserting the dangers of milk containing A1 proteins are available to the lay press and interested public, who may not be fully equipped to assess the bigger, evolving picture.

"Research is both complex and conflicting," says Emily Haller, RDN, who counsels patients for the division of gastroenterology at the University of Michigan's Michigan Medicine. "There is often some misinterpretation or exaggeration from the media, which is usually due to a poor understanding of nutrition science and research."

Unconfirmed studies linking the milk American families have been drinking to the development of chronic illnesses have the potential to frighten consumers. Dietitians can help by addressing these concerns with honesty and facts. "There are a lot of opinions and cherry-picking of information from studies regarding diet floating out on the internet that I hear about from my clients in clinic," Haller says. "Having a discussion and really getting down to the facts vs opinions is important and can put to rest some food-related fears, anxiety, and worry."

Addressing potentially unfounded fears should be done with caution. "As food and nutrition experts, we often have the urge to correct misinformation, but it's really important not to negate people's feelings," Lemond says. "Listening to someone's fears, validating them, and knowing when and how to correct them is an art."

Both Lemond and Haller recommend teaming up with the client or patient to reach an evidence-based understanding. "Ask questions: What have you heard? Where did you read it?" Lemond says. "Approach people with an open mind. When you show a client respect and gain their trust, they will be more likely to listen to you."

Haller isn't afraid to admit when she doesn't have all the answers. "If I don't have an answer, I often look up information with my patients right on the spot, and we do some research together," she says, "and if we can't get to the bottom of it, then I'm happy to look into it more and follow up."

Is Change Coming?
A2 beta-casein cow's milk has been available in Australia and New Zealand since the early 2000s, and it's reportedly difficult to find milk for sale in Australia that doesn't advertise its A2 beta-casein content on the label.3,14 The a2 Milk Company, which introduced A2-only milk to the marketplace, has expanded to China and Western Europe and already is selling product in parts of the United States, where it has partnered with Sprouts, Whole Foods, Kroger, and Albertson's food stores. How American consumers take to the product remains to be seen, but some small American farms already have begun converting their herds to A2-producing cows to meet possible interest.3

As milk from cows with the A2 beta-casein variant is introduced into the American marketplace, nutrition professionals may see an increase in questions related to the origins and effectiveness of this new product, as well as concerns or even fears regarding the safety of A1 proteins in milk. "People are starting to ask me about A2 dairy protein," Haller says. "It's still hard to find in the marketplace, so most have not had the opportunity to try it yet."

Making Recommendations
If clients or patients have digestive issues when consuming dairy, it's important to make sure they're clear on how the available milk products differ—and how they're the same. "Dairy with A2 beta-casein has just as much lactose as dairy with A1," Lemond says. "A lot of people have lactose intolerance. If a client switches over to milk from A2 cows and their symptoms don't go away, then the protein isn't the issue."

As long as the client doesn't have a milk allergy, it's safe to experiment. "Intolerance causes discomfort, but it doesn't have the potential to be immediately life-threatening like an allergy. Therefore, we have a little leeway in trying new things to see if they're helpful," Lemond says. "Milk with no A1 beta-casein protein is a more expensive product at this point. But if a patient has the financial means and wants to try it, there's no harm in seeing if they feel better drinking milk with only A2 beta-casein."

Haller agrees: "If someone is curious about milk with A2 protein and interested in seeing if it helps them, I would definitely encourage them to try it and see how they tolerate it," she says. "If they have a positive result, that's great."

As research progresses, the questions around possible negative health effects of BCM-7 from A1 protein in milk are bound to continue. Meanwhile, the percentage of people whose digestive issues arise from protein intolerance rather than lactose intolerance remains to be seen. Nevertheless, nutrition professionals are well positioned to assist their clients and patients in making sense of it all. "Registered dietitians can help translate evidenced-based recommendations into practical information and tips, as well as highlight when something isn't evidence-based," Haller says.

— Judith C. Thalheimer, RD, LDN, speaks and writes about all things nutrition-related from her home near Philadelphia.


References

1. Lactose intolerance. US National Library of Medicine, Genetics Home Reference website. https://ghr.nlm.nih.gov/condition/lactose-intolerance#statistics. Updated August 29, 2017.

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. Kral L. The health battle behind America's next milk trend. The Atlantic. January 27, 2017. https://www.theatlantic.com/science/archive/2017/01/a-tale-of-two-milks/514397/

4. European Food Safety Authority. Review of the potential health impact of β-casomorphins and related peptides. EFSA J. 2009;7(2):1-107.

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. Sodhi M, Mukesh M, Kataria RS, Mishra BP, Joshii BK. Milk proteins and human health: A1/A2 milk hypothesis. Indian J Endocrinol Metab. 2012;16(5):856.

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

10. Elliott RB, Harris DP, Hill JP, Bibby NJ, Wasmuth HE. Type I (insulin-dependent) diabetes mellitus and cow milk: casein variant consumption. Diabetologia. 1999;42(3):292-296.

11. Bell SJ, Grochoski GT, Clarke AJ. Health implications of milk containing beta-casein with the A2 genetic variant. Crit Rev Food Sci Nutr. 2006;46(1):93-100.

12. Laugesen M, Elliott R. Ischaemic heart disease, type 1 diabetes, and cow milk A1 beta-casein. N Z Med J. 2003;116(1168):U295.

13. Tailford KA, Berry CL, Thomas AC, Campbell JH. A casein variant in cow's milk is atherogenic. Atherosclerosis. 2003;170(1):13-19.

14. Nestle M. Milk marketing, Australian style. Food Politics website. http://www.foodpolitics.com/2016/01/milk-marketing-australian-style/. Published January 25, 2016.

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