Digestive issues attributed to lactose intolerance may be caused by A1 beta-casein protein, suggests study funded by a2 Milk

Digestive issues after drinking milk are typically attributed to milk protein allergy (which can be severe) or intolerance to lactose (milk sugars). But if both of these have been ruled out and people are still experiencing mild digestive discomfort, something else may be going on, claims the a2 Milk Company, which has developed a genetic test to identify cows that only produce A2 beta casein protein (most produce A1 and​ A2), so their milk can be segregated and marketed as a more ‘gut-friendly’ option.

While not everyone is convinced by the science underpinning the business (more on that HERE​​), a2 milk has secured almost 10% of the fluid milk market by value in Australia, and is hoping to achieve similar success in the US market (it hit shelves in California last year and is now available in chains from Kroger and The Fresh Market to Whole Foods Market).

Doubled-blind, randomized crossover trial ​

A new study​​ – published in the peer reviewed publication Nutrition Journal​​ – tested the a2 Milk Company’s theory in a doubled-blind, randomized 2x crossover trial with 45 Chinese Han subjects with self-reported lactose intolerance (chosen because of the high rate of perceived lactose intolerance in this population).

(Of the 45 subjects, 23 were confirmed to be lactose intolerant based on the results of a urinary galactose test.)

The study - conducted at the Department of Gastroenterology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine in Shanghai - aimed to compare the effects of milk containing A1 & A2 beta-casein (milk containing A1 only is not commercially available and is also not representative of consumer milk products) with those of milk containing exclusively A2 beta-casein on inflammation, symptoms of post-dairy digestive discomfort, and cognitive processing.

Each treatment period was 14 days with a 14-day washout period at baseline and between treatment periods, while the consumption of dairy products other than those provided was prohibited throughout the study.

According to The a2 Milk Company, originally all domesticated cows produced milk containing only the A2 type of beta-casein. However, owing to a natural genetic mutation, another milk protein (A1 beta-casein) appeared in Europe and spread throughout global herds, such that now, most contain A1 and A2. 

The results​: ‘​Exacerbation of GI symptoms associated with milk in lactose intolerant subjects may be related to A1 beta-casein rather than lactose per se’​

Compared with milk containing only A2 beta-casein, the consumption of milk containing both beta-casein types was associated with significantly greater post-dairy digestive discomfort symptoms; higher concentrations of inflammation-related biomarkers; longer gastrointestinal transit times and lower levels of short-chain fatty acids; and increased response time and error rate on the Subtle Cognitive Impairment Test (SCIT).

Consumption of milk containing both β-casein types was associated with worsening of PD3 symptoms relative to baseline in lactose tolerant and lactose intolerant subjects. Consumption of milk containing only A2 beta-casein did not aggravate PD3 symptoms relative to baseline (after washout of dairy products) in lactose tolerant and intolerant subjects.

Both milks contained equal amounts of lactose (4.8%), “which reinforces the concept that the differences in outcomes were driven by the presence or absence of A1 β-casein​”, said the authors.

“This study has demonstrated that consumption of milk containing A1 beta-casein in addition to A2 beta-casein worsens gastrointestinal symptoms, increases gastrointestinal transit time, increases serum inflammation markers, lowers total fecal SCFA content, slows cognitive processing speed and decreases processing accuracy compared with the baseline values. ​

“Consumption of milk containing only A2 beta-casein did not adversely affect these variables, indicating that the changes observed with milk containing both beta-casein types were attributable to the presence of A1 beta-casein. Furthermore, consumption of milk containing both types was associated with greater worsening of gastrointestinal symptoms and gastrointestinal transit time in lactose intolerant subjects than in lactose tolerant subjects, whereas milk containing only A2 beta-casein did not exacerbate these symptoms in lactose intolerant subjects.  ​

“These results suggest that the exacerbation of gastrointestinal symptoms associated with milk in lactose intolerant subjects may be related to A1 beta-casein rather than lactose per se.”​

Dr Greg Miller: More human studies needed before this moves from realm of theory to fact​

Asked by FoodNavigator-USA to comment on the study, Greg Miller, Ph.D., M.A.C.N., chief science officer at National Dairy Council, said he welcomed the fact that more human studies were being done to establish whether A1 beta-casein is responsible for digestive discomfort but stressed that this is only the second human clinical trial of which he is aware, and that both human studies "should really be considered to be pilot studies​" owing to th e small number of participants.

"By scientific standards, I still wouldn't call this anything more than a theory. The study design is good, but the numbers are small and the duration is short, it's a unique population, and there are still too many unknowns. I also don't know if the changes in biomarkers they measure are biologically significant.​

"The bottom line for consumers is that it's another choice in the marketplace, but my concern is that if we get ahead of the science, it could be confusing to consumers."​

Kasper Hettinga, PhD, assistant professor at the Dairy Science and Technology group of Wageningen University, told FoodNavigator-USA that this is the first paper about A2 milk that "makes sense" ​and "has been published at a journal with a moderate impact factor"​, although he noted that the number of participants was small and that "as often in science..... more research is needed at least for confirmation of the results."​

a2 milk has achieved ‘close to 85% weighted retail distribution across California’​

New Zealand-based a2 Milk Company, which is investing $20m over three years to fund its US market entry following moves into China and the UK, says a2 milk has been greeted with “high levels of acceptance​” from retailers in the US, where it claims a quarter of consumers experience digestive issues after consuming milk - only some of which can be attributed to cow's milk allergy or lactose intolerance.

a2 milk is sold in half-gallon cartons for $4.00-$4.50 with the strapline ‘The milk that might change everything’.​

New human clinical trial USA biomedical research center​ in the pipeline​

Asked about how the product is doing in the US, president Jeff O’Neill told us: “We’re in the early stages of our entry into the US and, at this point we’re well on our way to creating a loyal consumer base in California and bringing the benefits of the natural A2 protein to many who struggle to digest ordinary cows’ milk​

“We are pleased with the progress we have thus far in achieving close to 85% weighted retail distribution across California and looking forward to extending across new state. We are building strong credibility with the health care community and gaining support from science and medical practitioners, including initiating a new human clinical trial with a respected USA biomedical research center.”​

A2 cows are identified using non-invasive DNA test​

Cows that naturally produce milk rich in A2 beta casein are identified using a non-invasive DNA test which analyzes a sample hair from the tail. These cows are then separated to form A2 herds and their milk is segregated in the supply chain.

While Jersey and Guernsey milk are high in A2, a2 Milk is sourced exclusively from dairy cows that produce milk containing the A2 protein exclusively, according to the a2 Milk Company.

Source​: Nutrition Journal​  ​2016 15:35 DOI: 10.1186/s12937-016-0147-z

Title:​ 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​

Authors: ​Sun Jianqin, Xu Leiming, Xia Lu, Gregory W. Yelland, Jiayi Ni and Andrew J. Clarke