A1 Beta-casein-free Milk in Milk-intolerant Participants

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 Randomised Controlled Trial

This was a single-site, double-blind, randomised, controlled, crossover study, which aimed to compare the effects of conventional cow's milk (CON, containing both A1- and A2-types of beta-casein) versus milk free of A1-type beta-casein (A1PF milk) on gastrointestinal (GI) physiology and symptoms of digestive discomfort in non-regular milk drinkers with self-reported intolerance to conventional cow's milk. The study location was the Pennington Biomedical Research Center in Louisiana, USA. The study comprised a 2-week washout period, 2 weeks of milk consumption, crossover, a second 2-week washout period, and a second 2-week period of milk consumption. Eligible participants were stratified by sex to achieve an approximate 1:1 male to female ratio and were randomised to receive conventional cow's milk (sequence 1) or A1PF milk (sequence 2) during the first period of milk consumption. During the second period of milk consumption, participant groups underwent crossover to receive the alternate study milk.

Milk was consumed three times per day after meals, with 250 mL provided at each administration. During washout periods, participants were required to avoid all dairy products and use only rice milk to replace any normal dairy intake, and to avoid foods with very high fermentable oligosaccharides, disaccharides, monosaccharides, and polyols content, to avoid potential confounding of the symptoms experienced. Any medication, nutritional supplements, dairy products, acidophilus milk, or probiotics were prohibited during the study.

The study protocol and all related documentation were approved by the Pennington Biomedical Research Center Institution Review Board. The study was conducted in accordance with the principles of the Declaration of Helsinki and the Good Clinical Practice Guidelines of the International Conference on Harmonisation. All participants provided written informed consent prior to initiating any study procedures.

Study Overview

• Status: Completed
• Conditions: Digestive Discomfort
• Intervention / Treatment: Other: Dietary Supplement: conventional cow's milk consumption, and then A1PF milk consumption; Other: Dietary Supplement: A1PF milk consumption, and then conventional cow's milk consumption

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Pennington Biomedical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female participants aged 18 to 68 years
• Irregularly consumed milk
• Had self-reported mild-to-moderate digestive discomfort after milk consumption
• Had normal electrocardiograms and blood pressure during quiet respiration

Exclusion Criteria:

• Known allergies to dairy products
• Severe milk intolerance
• A history of faecal impaction
• Having suffered from GI disorders (e.g., irritable bowel syndrome, colitis, ulcerative colitis, or coeliac disease)
• Currently being administered drugs for cardiovascular or metabolic disease
• Trying to lose weight by following a diet or exercise regimen
• Took any appetite or weight loss drugs for the previous three months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Sequence 1; Sequence 1: a 2-week washout period, 2 weeks of conventional cow's milk consumption, crossover, a second 2-week washout period, and a second 2-week period of A1PF milk consumption.	Other: Dietary Supplement: conventional cow's milk consumption, and then A1PF milk consumption; Milk was consumed three times per day after meals, with 250 mL provided at each administration. During washout periods, participants were required to avoid all dairy products and use only rice milk.
Other: Sequence 2; Sequence 2: a 2-week washout period, 2 weeks of A1PF milk consumption, crossover, a second 2-week washout period, and a second 2-week period of conventional cow's milk consumption.	Other: Dietary Supplement: A1PF milk consumption, and then conventional cow's milk consumption; Milk was consumed three times per day after meals, with 250 mL provided at each administration. During washout periods, participants were required to avoid all dairy products and use only rice milk.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of bloating, abdominal pain, gas, borborygmus, eructation, and diarrhoea measured via Visual Analogue Scale (VAS)	VAS: 0 = never; 1 = rarely; 2 = frequently; 3 = all the time	At day 28 and day 56 (day 1 is study start)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gastric transit time, hours		At day 28 and day 56 (day 1 is study start)
Frequency of adverse events	Record if an adverse event is singe or intermettent.	From day 1 to day 56 (day 1 is study start)
Blood immunoglobulin (Ig)G, mg/dL		At day 28 and day 56 (day 1 is study start)
Fecal beneficial short-chain fatty acids (SCFA), mmol/g		At day 28 and day 56 (day 1 is study start)
Intensity of adverse events	Record if an adverse event is mild, moderate, or severe.	From day 1 to day 56 (day 1 is study start)

Collaborators and Investigators

• Sponsor: a2 Milk Company Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2017
• Primary Completion (Actual): March 27, 2019
• Study Completion (Actual): March 27, 2019

Study Registration Dates

• First Submitted: December 11, 2024
• First Submitted That Met QC Criteria: January 1, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 1, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: gastrointestinal symptoms; milk free of A1-type beta-casein; conventional cow's milk
• Other Study ID Numbers: 1016-065 Milk

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No