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. doi: 10.1186/s12937-017-0275-0.


Background: 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.

Methods: 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.

Results: 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 <0.27 mmol/L).

Conclusion: 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.

Trial registration: NCT02878876 , registered August 16, 2016. Retrospectively registered.

Keywords: Beta-casein; Intolerance; Lactase; Lactose.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Animals
  • Asian People*
  • Calcium, Dietary / administration & dosage
  • Caseins / administration & dosage*
  • Cross-Over Studies
  • Diet
  • Dietary Carbohydrates / administration & dosage
  • Dietary Fats / administration & dosage
  • Dietary Proteins / administration & dosage
  • Double-Blind Method
  • Fatty Acids / administration & dosage
  • Female
  • Food Analysis
  • Gastrointestinal Diseases / etiology
  • Humans
  • Lactase / metabolism
  • Lactose Intolerance / complications
  • Male
  • Middle Aged
  • Milk / chemistry*
  • Milk Hypersensitivity / complications
  • Milk Hypersensitivity / diagnosis*
  • Sodium, Dietary / administration & dosage
  • Young Adult


  • Calcium, Dietary
  • Caseins
  • Dietary Carbohydrates
  • Dietary Fats
  • Dietary Proteins
  • Fatty Acids
  • Sodium, Dietary
  • Lactase

Associated data

  • ClinicalTrials.gov/NCT02878876