Effect of the Consumption of Milk With Beta-casein A2A2, Milk With Beta-casein A1A2 and a Plant-based Drink on Metabolic Health in Adults: IMPA-CT Study (IMPA-CT)

The purpose of this study was to identify and compare the effects of daily consumption of A2 milk, conventional milk, and an oat drink on bone health, cardiometabolic health, and immune system function in adults. Although cow's milk plays an important role in human nutrition, its proteins-particularly β-caseins-exhibit significant genetic diversity. Conventional milk typically contains a mix of A1 and A2 β-casein variants, whereas A2 milk contains exclusively the A2/A2 variant. The key difference between the two lies in a single amino acid at position 67: variant A1 contains histidine, which allows digestive enzymes to release the opioid peptide β-casomorphin-7 (BCM-7), while variant A2 contains proline, which prevents the release of this peptide. Consequently, the study is trying to answer the question of whether 12 weeks of consuming 500 ml of A2 milk daily-thereby eliminating dietary exposure to BCM-7-results in different outcomes for bone health (the primary measure), as well as for cardiometabolic health and immune function, when compared to consuming conventional milk or a plant-based oat drink in healthy adults aged 30-60.

Study Overview

• Status: Recruiting
• Conditions: Healthy Participants
• Intervention / Treatment: Other: Consumption 500 ml of A2 milk; Other: Consumption 500 ml of A1 milk.; Other: Consumption 500 ml of oat drink.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jadwiga Hamulka Prof. dr hab., Prof. dr hab.; Phone Number: (48)0225937112; Email: jadwiga_hamulka@sggw.edu.pl

Study Locations

• Poland
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 02-776
      • Recruiting
      • Warsaw Univeristy of Life Science
      • Contact: Jadwiga Hamulka Prof. dr hab., Prof. dr hab.; Phone Number: 048 22 59 37 112; Email: jadwiga_hamulka@sggw.edu.pl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• aged 30 to 60 years,
• body mass index >18.5 or <30 kg/m2,
• no diagnosed chronic disease, i.e. diabetes, cancer, kidney disease,
• not taking medications/dietary supplements that may affect carbohydrate and/or lipid metabolism.

Exclusion Criteria:

• pregnancy or lactation in women,
• implanted medical materials such as: pacemaker, defibrillator, stent, metal suture in the heart or blood vessel, and implants,
• previous radiotherapy and/or chemotherapy,
• significantly modified diet (e.g., ketogenic, vegetarian, or ovo-vegetarian) and health condition requiring a specialist diet,
• unable to give informed consent,
• unable or unwilling to comply with the study procedures,
• have medical history of gastrointestinal surgery or disorders (inflammatory bowel disease, ulcerative colitis, coeliac disease, Crohn's disease), cardiorespiratory problems, uncontrolled diabetes mellitus, bleeding disorders.

Non-exclusion criteria:

• hypertension, or depression that are well-controlled with medical intervention.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A2 Milk Group; Habitual diet supplemented with 500 mL of milk A2 daily for 12 weeks; product available on the market	Other: Consumption 500 ml of A2 milk; The intervention study consisted of the consumption 500 ml of an appropriate product: A2 milk - daily for a 12 weeks.
Experimental: A1 Milk Group; Habitual diet with 500 mL of milk A1/A2 daily for 12 weeks; product available on the market	Other: Consumption 500 ml of A1 milk.; The intervention study consisted of the consumption 500 ml of an appropriate product: A1 milk - daily for a 12 weeks.
Experimental: Pland Drink Group; Habitual diet supplemented with 500 mL of oat drink daily for 12 weeks; product available on the market	Other: Consumption 500 ml of oat drink.; The intervention study consisted of the consumption 500 ml of an appropriate product: oat drink - daily for a 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Bone Mineral Density (BMD)	Assessment of changes in bone mineral density (BMD) using Dual-energy X-ray Absorptiometry (DEXA).	Baseline, and after 4, 8 and 12 weeks of intervention.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Plasma Procollagen Type 1 N-terminal Propeptide (P1NP) Concentration	Assessment of changes in P1NP as a biochemical marker of bone formation.	Baseline, and after 12 weeks of intervention.
Change from Baseline in Bone Alkaline Phosphatase (BALP) Concentration	Assessment of changes in BALP as a biochemical marker of bone formation.	Baseline, and after 12 weeks of intervention.
Change from Baseline in Plasma C-terminal Telopeptide of Type 1 Collagen (CTX-1) Concentration	Assessment of changes in plasma CTX-1 as a biochemical marker of bone resorption.	Baseline, and after 12 weeks of intervention.
Change from Baseline in Urinary Calcium Concentration	Assessment of changes in urinary calcium levels as a marker of bone resorption.	Baseline, and after 12 weeks of intervention.
Change from Baseline in Urinary Deoxypyridinoline Concentration	Assessment of changes in urinary deoxypyridinoline levels as a marker of bone resorption.	Baseline, and after 12 weeks of intervention.
Change from Baseline in Plasma Calcium Concentration	Assessment of changes in plasma calcium levels as a marker of bone homeostasis.	Baseline, and after 12 weeks of intervention.
Change from Baseline in 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] Concentration	Assessment of changes in 1,25(OH)2D3 levels as a marker of bone homeostasis.	Baseline, and after 12 weeks of intervention.
Change from Baseline in Body Mass Index (BMI)	Weight and height will be combined to report BMI in kg/m^2.	Baseline, and after 4, 8 and 12 weeks of intervention.
Change from Baseline in Waist-Hip Ratio (WHR)	Assessment of fat distribution calculated as waist measurement divided by hip measurement (unitless ratio).	Baseline, and after 4, 8 and 12 weeks of intervention.
Change from Baseline in Waist-to-Height Ratio (WHtR)	Assessment of fat distribution calculated as waist measurement divided by height (unitless ratio).	Baseline, and after 4, 8 and 12 weeks of intervention.
Change from Baseline in Ankle-Brachial Index (ABI)	Assessment of cardiovascular health using blood pressure measurements to calculate the Ankle-Brachial Index (ABI).	Baseline, and after 12 weeks of intervention.
Change from Baseline in Body Fat Mass	Assessment of changes in body fat mass, assessed by BIA and DEXA. Results will be reported in kilograms (kg).	Baseline, and after 4, 8 and 12 weeks of intervention.
Change from Baseline in Body Fat Percentage	Assessment of changes in total body fat content, assessed by BIA and DEXA. Results will be reported as a percentage (%).	Baseline, and after 4, 8 and 12 weeks of intervention.
Change from Baseline in Visceral Fat Area	Assessment of changes in visceral fat assessed by BIA and DEXA. Results will be reported in square centimeters (cm^2).	Baseline, and after 4, 8 and 12 weeks of intervention.
Change from Baseline in Cholesterol Concentration	Assessment of changes in total cholesterol, High-Density Lipoprotein (HDL) and Low-Density Lipoprotein (LDL) Cholesterol Concentration as part of the lipid profile.	Baseline, and after 12 weeks of intervention.
Change from Baseline in Triglycerides Concentration	Assessment of changes in triglycerides as part of the lipid profile.	Baseline, and after 12 weeks of intervention.
Change from Baseline in Fasting Glucose Concentration	Assessment of changes in fasting blood glucose levels.	Baseline, and after 12 weeks of intervention.
Change from Baseline in Fasting Insulin Concentration	Assessment of changes in fasting insulin levels.	Baseline, and after 12 weeks of intervention.
Change from Baseline in Insulin-like Growth Factor-1 (IGF-1) Concentration	Assessment of changes in IGF-1 levels.	Baseline, and after 12 weeks of intervention.
Change from Baseline in IGF-Binding Protein-3 (IGFBP-3) Concentration	Assessment of changes in IGFBP-3 levels.	Baseline, and after 12 weeks of intervention.
Change from Baseline in High-Sensitivity C-Reactive Protein (hsCRP) Concentration	Assessment of changes in hsCRP as a marker of systemic inflammation.	Baseline, and after 12 weeks of intervention.
Change from Baseline in Uric Acid Concentration at 12 Weeks	Assessment of changes in uric acid levels.	Baseline, and after 12 weeks of intervention.
Change from Baseline in Creatinine Concentration	Assessment of changes in creatinine levels.	Baseline, and after 12 weeks of intervention.
Baseline, and after 12 weeks of intervention.	Assessment of changes in plasma levels of Immunoglobulin A (IgA) as an indicator of immune system functioning.	Baseline, and after 12 weeks of intervention.
Change from Baseline in Immunoglobulin G (IgG) Concentration	Assessment of changes in plasma levels of Immunoglobulin G (IgG) as an indicator of immune system functioning.	Baseline, and after 12 weeks of intervention.
Change from Baseline in Allergen-specific Immunoglobulin E (sIgE) Concentration	Assessment of changes in allergen-specific Immunoglobulin E (sIgE) as a marker for potential casein allergy.	Baseline, and after 12 weeks of intervention.

Collaborators and Investigators

• Sponsor: Dawid Madej

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2025
• Primary Completion (Estimated): April 23, 2026
• Study Completion (Estimated): April 23, 2026

Study Registration Dates

• First Submitted: January 29, 2026
• First Submitted That Met QC Criteria: February 20, 2026
• First Posted (Actual): February 27, 2026

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 20, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Health Care Economics and Organizations; Economics
• Other Study ID Numbers: IMPA-CT/38/RKE/2024; SUP-RIM (MEiN/2023/DPI/2866) (Other Grant/Funding Number: Ministry of Science and Higher Education of Poland)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No