A1-Free vs. Conventional Milk Metabolic Response Study

Официальное название

A Randomized Crossover Study Evaluating Postprandial Glucose and Insulin Responses to A1-Free and Conventional Milk With and Without a Delayed Lactose Challenge in Healthy Adults

Обзор

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.

Подробное описание

Postprandial glucose and insulin responses are important indicators of metabolic health, even in individuals without diagnosed metabolic disease. The rate and pattern of nutrient digestion and absorption can influence these responses, and emerging evidence suggests that differences in milk protein composition, specifically the presence or absence of A1 beta-casein, may alter gastrointestinal function and metabolic outcomes.

This study is a randomized, double-blind, crossover trial designed to evaluate the effects of A1-free milk compared to conventional milk on postprandial metabolic responses in healthy adults. Participants will complete four experimental conditions in random order: (1) lactose-containing A1-free milk, (2) lactose-containing conventional milk, (3) lactose-free A1-free milk followed by a delayed lactose challenge, and (4) lactose-free conventional milk followed by a delayed lactose challenge.

The inclusion of both lactose-containing and lactose-free conditions allows for evaluation of two complementary questions. First, direct comparisons between lactose-containing A1-free and conventional milk will assess whether milk protein composition influences postprandial glucose and insulin responses under typical consumption conditions. Second, the lactose-free preload conditions, combined with a standardized delayed lactose challenge, are designed to evaluate whether prior milk consumption modifies subsequent metabolic responses to lactose exposure. This approach provides insight into potential differences in digestive kinetics, including gastric emptying, nutrient delivery, and lactose digestion and absorption.

During each study visit, participants will consume a standardized milk-based intervention following an overnight fast. In the lactose-free conditions, a lactose beverage matched to the amount of lactose typically present in the milk will be administered 60 minutes after milk consumption. Blood samples will be collected at multiple timepoints over a postprandial period to measure glucose and insulin concentrations and characterize response patterns, including early-phase responses and overall exposure.

Secondary and exploratory outcomes include breath hydrogen testing as a non-invasive marker of carbohydrate fermentation and lactose maldigestion, as well as gastrointestinal symptom assessments using validated questionnaires. These measures will be used to provide additional context for interpreting metabolic responses across conditions.

The crossover design allows each participant to serve as their own control, improving statistical power and reducing variability. The findings from this study will help clarify whether differences in milk protein composition influence metabolic responses and whether prior exposure to lactose-free milk alters the body's handling of lactose consumed at a later time.

Вмешательства

• Пищевая добавка Lactose-Containing A1-Free Milk
  A lactose-containing milk beverage containing A2 beta-casein and no A1 beta-casein, consumed during one experimental study visit.
• Пищевая добавка Lactose-Containing Conventional Milk
  A lactose-containing conventional milk beverage containing both A1 and A2 beta-casein, consumed during one experimental study visit.
• Пищевая добавка Lactose-Free A1-Free Milk With Delayed Lactose Drink
  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.
• Пищевая добавка Lactose-Free Conventional Milk With Delayed Lactose Drink
  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.

Первичные конечные точки

• Postprandial Plasma Insulin Incremental Area Under the Curve (iAUC) [Срок оценки: 0 to 180 minutes post-intervention during each study visit]
• Postprandial Plasma Glucose Incremental Area Under the Curve (iAUC) [Срок оценки: 0 to 180 minutes post-intervention during each study visit]

Вторичные конечные точки (6)

• Early-Phase Postprandial Glucose and Insulin Response [Срок оценки: 0 to 60 minutes post-intervention]
• Time to Peak Plasma Glucose and Insulin Concentrations (Tmax) [Срок оценки: 0 to 180 minutes post-intervention]
• Circulating Metabolite Responses [Срок оценки: 0, 30, 60, and 120 minutes]
• Breath Hydrogen Concentrations [Срок оценки: Baseline and every 30 minutes from 0 to 180 minutes post-intervention]
• Gastrointestinal Symptom Scores [Срок оценки: Baseline and at 60, 120, and 180 minutes post-intervention]
• Urinary Galactose Concentrations [Срок оценки: Baseline and 180 minutes post intervention]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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
• Height: \_\_\_ Weight: \_\_\_ BMI: \_\_\_ Weighing <16.5 kg or Body mass index > 35 kg/m2
• You have participated in another clinical trial or used an investigational product within the past 30 days
• You have any other condition that, as determined by the study team, would make participation unsafe or interfere with study results

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Тройное слепое

Основная цель

Другое

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• 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
• 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
• 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
• 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
• 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
• 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

Идентификаторы

NCT: NCT07567443 · IRB 2026-00000555

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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