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Effects of cow's milk beta-casein variants on symptoms of milk intolerance in Chinese adults: a multicentre, randomised controlled study

He M, Sun J, Jiang ZQ, Yang YX. (2017) Nutr J. 16(1) 72. doi: 10.1186/s12937-017-0275-0. 

Web URL: Read this and related abstracts on PubMed here. Free full text of this article is available online



A major protein component of cow's milk is β-casein. The most frequent variants in dairy herds are A1 and A2. Recent studies showed that milk containing A1 β-casein promoted intestinal inflammation and exacerbated gastrointestinal symptoms. However, the acute gastrointestinal effects of A1 β-casein have not been investigated. This study compared the gastrointestinal effects of milk containing A1 and A2 β-casein versus A2 β-casein alone in Chinese adults with self-reported lactose intolerance.


In this randomised, crossover, double-blind trial, with a 3-day dairy washout period at baseline, subjects were randomised to consume 300 mL of milk containing A1 and A2 β-casein (ratio 58:42; conventional milk) or A2 β-casein alone; subjects consumed the alternative product after a 7-day washout period. Urine galactose was measured at baseline after a 15 g lactose load.

Subjects completed 9-point visual analogue scales for gastrointestinal symptoms (borborygmus, flatulence, bloating, abdominal pain, stool frequency, and stool consistency) at baseline and at 1, 3, and 12 h after milk consumption.


A total of 600 subjects were included. All six symptom scores at 1 and 3 h were significantly lower after consuming A2 β-casein versus conventional milk (all P<0.0001). At 12 h, significant differences remained for bloating, abdominal pain, stool frequency, and stool consistency (all P<0.0001).

Symptom scores were consistently lower with A2 β-casein in both lactose absorbers (urinary galactose ≥0.27 mmol/L) and lactose malabsorbers (urinary galactose


Milk containing A2 β-casein attenuated acute gastrointestinal symptoms of milk intolerance, while conventional milk containing A1 β-casein reduced lactase activity and increased gastrointestinal symptoms compared with milk containing A2 β-casein.

Thus, milk-related gastrointestinal symptoms may result from the ingestion of A1 β-casein rather than lactose in some individuals.


NCT02878876 , registered August 16, 2016. Retrospectively registered.


Beta-caseinIntolerance; Lactase; Lactose


This new multi-centre clinical trial was designed to further explore findings from an earlier clinical trial which found that cows' milk containing only the A2 form of the beta-casein protein was well tolerated by Chinese adults with self-reported lactose intolerance, while standard cows' milk - which contains both A1 and A2 beta-casein - was not.

The primary aim was therefore to test the hypothesis that consuming standard cows’ milk (containing a mixture of A1 and A2 beta-casein), would lead to more acute gastrointestinal (GI) symptoms than milk containing A2 beta-casein only in adults with self-reported ‘milk intolerance', including lactose intolerance. 

A secondary aim was to investigate participants’ ability to metabolise and break down the milk sugar, lactose (i.e. an index of their ‘lactose intolerance’) in relation to their reported GI symptoms following consumption of each type of milk.

Results strongly supported the primary hypothesis tested, as after 3 hours:

  • all 6 of the gastrointestinal and digestive symptoms assessed were significantly lower after consumption of milk containing A2 beta-casein only, compared with cows’ milk containing both A1 and A2 beta-casein. 
Differences for 4 of the 6 symptoms also remained significant 12 hours after consumption of a single 300ml milk serving.

The GI symptoms assessed were of the kind typically associated with intolerance to lactose (but which are also common in other conditions such as Irritable Bowel Syndrome), including

  • abdominal pain
  • bloating
  • flatulence (passing wind)
  • loose stools
  • high stool frequency
  • borborygmus (abdominal 'gurgling').

Both types of milk contained the same amount of lactose, but the increases in urinary galactose (UG) concentrations observed 3 hours after consumption were significantly higher for A2 milk than for standard milk. 

Higher UG concentrations are consistent with greater activity of lactase, a key enzyme involved in the breakdown and excretion of lactose. These findings therefore support the secondary hypothesis - that lactase activity might be influenced by the type of beta-casein present in milk - although further studies are needed to investigate this.

Of particular interest is that the significant differences in GI symptoms were observed not only in ‘lactose absorbers’ (i.e. those whose lactose absorption was within normal limits as assessed by their change in UG following milk consumption), but also in those classified as lactose malabsorbers (i.e. with UG changes suggestive of lactose intolerance).

This suggests that

  • in some people, the type of beta-casein in milk may influence gut and digestive symptoms irrespective of the ability to break down lactose and that
  • some people with confirmed lactose intolerance may be able to tolerate A2 milk, but not standard cows milk 

Again, however, further studies will be needed to confirm these possibilities, as UG changes provide only an indirect index of lactase activity / lactose intolerance.

See also:

And for more information on the possible links between A1 milk intolerance and some symptoms of Autistic Spectrum Disorders and other developmental and mental health conditions, see: