Comparative effects of conventional cow’s milk versus milk free of A1-type beta-casein on gastrointestinal physiology and symptoms of digestive discomfort in participants intolerant to conventional cow’s milk: a pilot randomised controlled trial

Cow’s milk is an important source of nutrients supporting human growth and development as well as adult health, but it can be associated with unwanted gastrointestinal (GI) symptoms. These symptoms are often attributed to lactose, but may instead be partly due to peptides released during digestion. This exploratory study aimed to compare the effects of consuming milk free of A1-type beta-casein (A1PF milk) with those of conventional cow’s milk (containing both A1- and A2-types of beta-casein) on GI symptoms in individuals who usually suffer from mild-to-moderate digestive discomfort after milk consumption. This was a single-site, double-blind, randomised, controlled, crossover study in non-regular milk drinkers (aged 18–68 years) with self-reported intolerance to cow’s milk. Participants consumed either A1PF milk or conventional milk three times per day after meals. GI symptoms, GI parameters (assessed using a SmartPill™ ingestible sensor) and blood and faecal laboratory measurements were assessed. No statistically significant between-group differences were seen in the frequency and consistency of stool; overall and individual GI symptoms; in GI parameters, including transit time; or in laboratory measurements including immunoglobulin (Ig)G, IgE, IgG1, interleukin-4, acetate, butyrate, propionate, short-chain fatty acid levels, or thiol levels. Among participants consuming A1PF milk, higher urinary galactose (U-gal) levels were correlated with smaller increases from baseline in patient-reported abdominal pain (r = − 0.296, p < 0.05); this correlation was not observed in participants consuming conventional milk. Additionally, higher U-gal levels were correlated with a greater increase in gastric transit time (r = 0.409, p < 0.05) and with a greater increase in glutathione level (r = 0.314, p < 0.05) only in participants consuming A1PF milk, but not in those consuming conventional milk. Significant correlations between higher U-gal values and changes in GI variables were seen in participants consuming A1PF milk, including increased glutathione, a smaller increase from baseline in abdominal pain, and a greater increase in gastric transit time. In terms of GI symptoms, individuals with higher baseline U-gal levels (indicating preserved lactase activity) may benefit from A1PF milk more than those with lower baseline U-gal levels. NCT06763185.