A1-Free vs. Conventional Milk Metabolic Response Study

NCT07567443 | Not Yet Recruiting

• 1 other identifier: IRB 2026-00000555
• Study Type: interventional
• Target: 35
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will examine how different types of milk affect blood sugar and insulin responses after eating. Specifically, the study compares milk that contains only A2 beta-casein protein (A1-free milk) to conventional milk, which contains both A1 and A2 proteins. Participants will complete four study visits in which they will consume different milk-based beverages. These include lactose-containing milk and lactose-free milk followed by a lactose drink given later. Blood samples will be collected over several hours to measure glucose and insulin responses. Breath tests and questionnaires will also be used to assess digestion and gastrointestinal symptoms. The goal of this study is to determine whether milk protein type influences metabolic responses and whether consuming lactose-free milk affects how the body processes lactose when it is consumed later.

Conditions

Postprandial Glucose Response; Insulin Response; Lactose Digestion; Postprandial Metabolism

Keywords

A1 beta-casein; A1-free milk; Postprandial glucose; Insulin response; Postprandial Glycemia; Digestive Kinetics; Lactose digestion; Metabolic response

Outcome Measures

Primary Outcomes (2)

• Postprandial Plasma Insulin Incremental Area Under the Curve (iAUC)

  Incremental area under the curve (iAUC) for plasma insulin concentrations following consumption of each study condition, measured from serial blood samples collected via an indwelling catheter.

  0 to 180 minutes post-intervention during each study visit

• Postprandial Plasma Glucose Incremental Area Under the Curve (iAUC)

  Incremental area under the curve (iAUC) for plasma glucose concentrations following consumption of each study condition, measured from serial blood samples collected via an indwelling catheter.

  0 to 180 minutes post-intervention during each study visit

Secondary Outcomes (6)

• Early-Phase Postprandial Glucose and Insulin Response

  0 to 60 minutes post-intervention

• Time to Peak Plasma Glucose and Insulin Concentrations (Tmax)

  0 to 180 minutes post-intervention

• Circulating Metabolite Responses

  0, 30, 60, and 120 minutes

• Breath Hydrogen Concentrations

  Baseline and every 30 minutes from 0 to 180 minutes post-intervention

• Gastrointestinal Symptom Scores

  Baseline and at 60, 120, and 180 minutes post-intervention

Study Arms (4)

Lactose-Containing A1-Free Milk

EXPERIMENTAL

Participants consume lactose-containing A1-free milk during one study visit. Blood, breath hydrogen, urine, and gastrointestinal symptom measures are collected over the 180 minute postprandial period.

Dietary Supplement: Lactose-Containing A1-Free Milk

Lactose-Containing Conventional Milk

EXPERIMENTAL

Participants consume lactose-containing conventional milk containing both A1 and A2 beta-casein during one study visit. Blood, breath hydrogen, urine, and gastrointestinal symptom measures are collected over the 180 minute postprandial period.

Dietary Supplement: Lactose-Containing Conventional Milk

Lactose-Free A1-Free Milk With Delayed Lactose Drink

EXPERIMENTAL

Participants consume lactose-free A1-free milk followed by a lactose drink administered 60 minutes after milk consumption. Blood, breath hydrogen, and gastrointestinal symptom measures are collected over the 180 minute postprandial period.

Dietary Supplement: Lactose-Free A1-Free Milk With Delayed Lactose Drink

Lactose-Free Conventional Milk With Delayed Lactose Drink

EXPERIMENTAL

Participants consume lactose-free conventional milk containing both A1 and A2 beta-casein followed by a lactose drink administered 60 minutes after milk consumption. Blood, breath hydrogen, and gastrointestinal symptom measures are collected over the 180 minute postprandial period.

Dietary Supplement: Lactose-Free Conventional Milk With Delayed Lactose Drink

Interventions

Lactose-Containing A1-Free Milk DIETARY_SUPPLEMENT

A lactose-containing milk beverage containing A2 beta-casein and no A1 beta-casein, consumed during one experimental study visit.

Also known as: A1-free milk, A2 milk

Lactose-Containing A1-Free Milk

Lactose-Containing Conventional Milk DIETARY_SUPPLEMENT

A lactose-containing conventional milk beverage containing both A1 and A2 beta-casein, consumed during one experimental study visit.

Also known as: Conventional milk, A1/A2 milk

Lactose-Containing Conventional Milk

Lactose-Free A1-Free Milk With Delayed Lactose Drink DIETARY_SUPPLEMENT

A lactose-free A1-free milk beverage consumed at the start of the study visit, followed by a lactose drink administered 60 minutes after milk consumption. The lactose drink is matched to the amount of lactose expected in the milk serving.

Lactose-Free A1-Free Milk With Delayed Lactose Drink

Lactose-Free Conventional Milk With Delayed Lactose Drink DIETARY_SUPPLEMENT

A lactose-free conventional milk beverage containing both A1 and A2 beta-casein consumed at the start of the study visit, followed by a lactose drink administered 60 minutes after milk consumption. The lactose drink is matched to the amount of lactose expected in the milk serving.

Lactose-Free Conventional Milk With Delayed Lactose Drink

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability/desire to provide informed consent
• Are between 18 and 65 years of age
• Are generally healthy, with no known metabolic or gastrointestinal conditions that would affect digestion or metabolism
• Are willing to consume milk-based beverages and lactose-containing drinks as part of the study
• Are willing to fast overnight (approximately 10-12 hours) prior to study visits and follow study instructions (e.g., diet and activity restrictions)
• Are willing to attend all study visits and complete all study procedures (blood draws, breath tests, urine samples, questionnaires)
• Are able to understand and provide written informed consent in English.

You may not qualify if:

• You have a known allergy to milk or dairy products
• You are currently pregnant, planning to become pregnant, or breastfeeding
• You currently smoke or have used tobacco or nicotine-containing products within the past 3 months
• You have a history of excessive alcohol use within the past 30 days
• You have been diagnosed with diabetes (Type 1 or Type 2), prediabetes, or other metabolic conditions that affect glucose or insulin responses (such as insulin resistance, metabolic syndrome, or polycystic ovary syndrome \[PCOS\])
• You have a history of gastrointestinal conditions that may affect digestion or absorption (such as inflammatory bowel disease, Crohn's disease, ulcerative colitis, celiac disease, or severe irritable bowel syndrome)
• You have had gastrointestinal surgery that alters normal digestive function (such as bariatric surgery or gastric bypass)
• You have other medical conditions that may affect digestion or interfere with study results (such as Past or present: Organ transplant, chronic pancreatitis, pancreatic insufficiency, symptomatic biliary disease, Celiac disease, chronic constipation, diverticulosis, inflammatory bowel disease (IBD), ulcerative colitis (UC), Crohn's disease (CD), small intestine bacterial overgrowth syndrome (SIBO), gastroparesis, gastro-esophageal reflux disease (GERD), Irritable Bowel Syndrome (IBS) or any other medical condition with symptoms that could confound collection of adverse events.)
• You have used medications or supplements known to affect glucose metabolism, digestion, or gastrointestinal function within the following timeframes prior to enrollment:
• Within 4 weeks: insulin, metformin, GLP-1 receptor agonists, corticosteroids, digestive enzymes, fiber supplements, and all oral or IV antibiotics
• Within 2 weeks: bismuth-containing compounds (e.g., Pepto-Bismol) and proton pump inhibitors or acid suppressors (e.g., omeprazole \[Prilosec\], lansoprazole \[Prevacid\], esomeprazole \[Nexium\], pantoprazole \[Protonix\], rabeprazole \[Aciphex\])
• Within 1 week: laxatives and stool softeners (e.g., Miralax, Colace, senna, lactulose, Citrucel, Metamucil, Fibercon), probiotics and prebiotics, gastrointestinal motility agents (e.g., Reglan, Linzess, Amitiza), and antidiarrheal medications (e.g., loperamide \[Imodium\], Lomotil)
• You have had a recent infection within the past 30 days
• You have been diagnosed with Human Immunodeficiency Virus (HIV), hepatitis B, or hepatitis C
• You are currently undergoing chemotherapy

Sponsors & Collaborators

• Purdue University: lead

Related Publications (6)

• Shrestha A, Samuelsson LM, Sharma P, Day L, Cameron-Smith D, Milan AM. Comparing Response of Sheep and Cow Milk on Acute Digestive Comfort and Lactose Malabsorption: A Randomized Controlled Trial in Female Dairy Avoiders. Front Nutr. 2021 Feb 15;8:603816. doi: 10.3389/fnut.2021.603816. eCollection 2021.

  PMID: 33659266 BACKGROUND

• Ramakrishnan M, Zhou X, Dydak U, Savaiano DA. Gastric Emptying of New-World Milk Containing A1 and A2 Beta-Casein Is More Rapid as Compared to Milk Containing Only A2 Beta-Casein in Lactose Maldigesters: A Randomized, Cross-Over Trial Using Magnetic Resonance Imaging. Nutrients. 2023 Feb 4;15(4):801. doi: 10.3390/nu15040801.

  PMID: 36839159 BACKGROUND

• Nilsson M, Stenberg M, Frid AH, Holst JJ, Bjorck IM. Glycemia and insulinemia in healthy subjects after lactose-equivalent meals of milk and other food proteins: the role of plasma amino acids and incretins. Am J Clin Nutr. 2004 Nov;80(5):1246-53. doi: 10.1093/ajcn/80.5.1246.

  PMID: 15531672 BACKGROUND

• Gunnerud U, Holst JJ, Ostman E, Bjorck I. The glycemic, insulinemic and plasma amino acid responses to equi-carbohydrate milk meals, a pilot- study of bovine and human milk. Nutr J. 2012 Oct 12;11:83. doi: 10.1186/1475-2891-11-83.

  PMID: 23057765 BACKGROUND

• Sun L, Tan KWJ, Han CMS, Leow MK, Henry CJ. Impact of preloading either dairy or soy milk on postprandial glycemia, insulinemia and gastric emptying in healthy adults. Eur J Nutr. 2017 Feb;56(1):77-87. doi: 10.1007/s00394-015-1059-y. Epub 2015 Oct 6.

  PMID: 26439722 BACKGROUND

• Phillips LK, Deane AM, Jones KL, Rayner CK, Horowitz M. Gastric emptying and glycaemia in health and diabetes mellitus. Nat Rev Endocrinol. 2015 Feb;11(2):112-28. doi: 10.1038/nrendo.2014.202. Epub 2014 Nov 25.

  PMID: 25421372 BACKGROUND

Study Officials

• Dennis A Savaiano, PhD

  Purdue University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laura A Robinson, PhD

CONTACT

908-442-3688; ldelvers@purud.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Virginia C. Meredith Professor of Nutrition Policy and Dean Emeritus Director, CTSI, IDOH Connections IN Health Dean Emeritus

Study Record Dates

• First Submitted: April 28, 2026
• First Posted: May 5, 2026
• Study Start (Estimated): June 15, 2026
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): January 31, 2027
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share