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 Apr 2:15:35. doi: 10.1186/s12937-016-0147-z.


Background: Cows' milk generally contains two types of β-casein, A1 and A2 types. Digestion of A1 type can yield the peptide β-casomorphin-7, which is implicated in adverse gastrointestinal effects of milk consumption, some of which resemble those in lactose intolerance. This study aimed to compare the effects of milk containing A1 β-casein with those of milk containing only A2 β-casein on inflammation, symptoms of post-dairy digestive discomfort (PD3), and cognitive processing in subjects with self-reported lactose intolerance.

Methods: Forty-five Han Chinese subjects participated in this double-blind, randomized, 2 × 2 crossover trial and consumed milk containing both β-casein types or milk containing only A2 β-casein. Each treatment period was 14 days with a 14-day washout period at baseline and between treatment periods. Outcomes included PD3, gastrointestinal function (measured by smart pill), Subtle Cognitive Impairment Test (SCIT), serum/fecal laboratory biomarkers, and adverse events.

Results: Compared with milk containing only A2 β-casein, the consumption of milk containing both β-casein types was associated with significantly greater PD3 symptoms; higher concentrations of inflammation-related biomarkers and β-casomorphin-7; longer gastrointestinal transit times and lower levels of short-chain fatty acids; and increased response time and error rate on the 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 β-casein did not aggravate PD3 symptoms relative to baseline (i.e., after washout of dairy products) in lactose tolerant and intolerant subjects.

Conclusions: Consumption of milk containing A1 β-casein was associated with increased gastrointestinal inflammation, worsening of PD3 symptoms, delayed transit, and decreased cognitive processing speed and accuracy. Because elimination of A1 β-casein attenuated these effects, some symptoms of lactose intolerance may stem from inflammation it triggers, and can be avoided by consuming milk containing only the A2 type of beta casein.

Trial registration: ClinicalTrials.gov/NCT02406469.

Keywords: Cognitive processing; Cows’ milk; Gastrointestinal function; Lactose intolerance; β-casein.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Asian People
  • Biomarkers / blood
  • Caseins / adverse effects
  • Caseins / analysis*
  • Cattle
  • Cognition*
  • Cross-Over Studies
  • Digestion
  • Double-Blind Method
  • Endorphins / blood
  • Feces / chemistry
  • Female
  • Gastrointestinal Tract / physiopathology*
  • Humans
  • Inflammation / blood
  • Lactose Intolerance / blood*
  • Male
  • Middle Aged
  • Milk / adverse effects
  • Milk / chemistry*
  • Peptide Fragments / blood
  • Self Report


  • Biomarkers
  • Caseins
  • Endorphins
  • Peptide Fragments
  • beta-casomorphin 7

Associated data

  • ClinicalTrials.gov/NCT02406469