Effects of Intact and Disrupted Milk Fat Globule Membrane on Postprandial Metabolic Response to High-fat Dairy in Healthy Individuals

The aim of the study is to investigate the effects of milk fat globule membrane (MFGM) content and intactness on postprandial metabolic response to a high-fat meal in humans.

The investigators hypothesize that MFGM content and intactness alters the postprandial lipid profile and substrate metabolism in healthy individuals after consumption of a high-fat meal.

Study Overview

• Status: Completed
• Conditions: Postprandial Lipid Metabolism
• Intervention / Treatment: Dietary supplement: Sandwich with butter-like dairy product (40g milk fat) with intact MFGM. One sandwich for breakfast and one sandwich for lunch.; Dietary supplement: Sandwich with butter-like dairy product (40g milk fat) with disrupted MFGM. One sandwich for breakfast and one sandwich for lunch.; Dietary supplement: Sandwich with butter-like dairy product (40g milk fat) without MFGM. One sandwich for breakfast and one sandwich for lunch.

Detailed Description

The subjects will be invited for four visits in total: one screening visit and three test days separated by a one-week washout period. At the test days, subjects will consume two high-fat meals composed of milk fat with intact MFGM, destroyed MFGM, and without MFGM, respectively. The first meal will be consumed as breakfast and the second meal will be consumed as lunch. Test meals will be isocaloric and with similar macronutrient composition. The meal will consist of a sandwich with a butter-like dairy product.

The three trial days will be completely alike, besides the interventions.

Subjects will arrive at the research lab the night before test day and stay inside a metabolic chamber to acclimatize.

The participants will have one intravenous (iv.) access placed in the elbow on the three trial days where blood samples will be collected at 15, 30, 60, 90, 120, 150 and 180 min after each test meal (breakfast and lunch).

Immediately after consuming each of the two test meals, the subjects will take 1,500mg paracetamol to determine ventricular emptying rate using the acetaminophen test. After this, the subjects can lay in the bed and watch TV, iPad, or work on their laptop.

Before and every hour after consumption of the test meals, the subjects will be asked to fill out an appetite questionnaire (visual analogue scale). At the end of the day the participants will be offered an "ad libitum meal" to measure if MFGM content and intactness influences ad libitum intake of calories at the next meal.

An one-way mixed model of linear regression will be used to compare postprandial area under the curve, ventricular emptying, and ad libitum food intake between the three test days. Secondary outcomes will be analyzed using a two-way mixed model of linear regression with repeated measurements.

Based on the results from a previous study that investigated the effects of the fat and protein structure in dairy products on postprandial triglycerides (20), the investigators will need 11 subjects to detect a 15% decrease in postprandial triglyceride AUC (α=0.05, β=0.80). To account for potential missing values, 12 subjects will be included in total.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • Steno Diabetes Center Aarhus, Aarhus University Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 18-40 years
• Written and informed consent
• HbA1c < 48 mmol/l

Exclusion Criteria:

• Medicine with an impact on blood glucose, lipid profile, or blood pressure and birth control pills
• BMI > 30kg/m2
• Affected screening blood sample as evaluated by the clinical responsible investigator
• Severe claustrophobia
• Lactose intolerance
• Doesn't speak and understand Danish
• Commitment to special diets

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High-fat meal with intact MFGM	Dietary supplement: Sandwich with butter-like dairy product (40g milk fat) with intact MFGM. One sandwich for breakfast and one sandwich for lunch.; 1) Sandwich with butter-like dairy product (40g milk fat) with intact MFGM.
Experimental: High-fat meal with destroyed MFGM	Dietary supplement: Sandwich with butter-like dairy product (40g milk fat) with disrupted MFGM. One sandwich for breakfast and one sandwich for lunch.; 2) Sandwich with butter-like dairy product (40g milk fat) with disrupted MFGM.
Experimental: High-fat meal without MFGM	Dietary supplement: Sandwich with butter-like dairy product (40g milk fat) without MFGM. One sandwich for breakfast and one sandwich for lunch.; 3) Sandwich with butter-like dairy product (40g milk fat) without MFGM.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in postprandial triglycerides measured as area under the curve (AUC).	Difference in triglycerides AUC after the intervention between high-fat meal with intact MFGM, high-fat meal with destroyed MFGM, and high-fat meal without MFGM.	-60 to 180 minutes after first intervention (first meal), 0-180 minuter after second intervention (second high-fat meal)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in concentration of GLP-1		-60 to 180 minutes after first intervention (first high-fat meal), 0-180 minutes after second intervention (second high-fat meal)
Difference in concentration of Ghrelin		-60 to 180 minutes after first intervention (first high-fat meal), 0-180 minutes after second intervention (second high-fat meal)
Difference in concentration of LEAP2		-60 to 180 minutes after first intervention (first high-fat meal), 0-180 minutes after second intervention (second high-fat meal)
Difference in concentration of FFA		-60 to 180 minutes after first intervention (first high-fat meal), 0-180 minutes after second intervention (second high-fat meal)
Difference in concentration of Insulin		-60 to 180 minutes after first intervention (first high-fat meal), 0-180 minutes after second intervention (second high-fat meal)
Difference in concentration of glucagon		-60 to 180 minutes after first intervention (first high-fat meal), 0-180 minutes after second intervention (second high-fat meal)
Difference in concentration of cholesterol (total, LDL and HDL)		-60 to 180 minutes after first intervention (first high-fat meal), 0-180 minutes after second intervention (second high-fat meal)
Difference in concentration of GIP		-60 to 180 minutes after first intervention (first high-fat meal), 0-180 minutes after second intervention (second high-fat meal)
Difference in concentration of CCK		-60 to 180 minutes after first intervention (first high-fat meal), 0-180 minutes after second intervention (second high-fat meal)
Difference in concentration concentration of Gastrin		-60 to 180 minutes after first intervention (first high-fat meal), 0-180 minutes after second intervention (second high-fat meal)
Difference in concentration concentration of GDF15		-60 to 180 minutes after first intervention (first high-fat meal), 0-180 minutes after second intervention (second high-fat meal)
Difference in concentration of LPS-BP (Lipopolysaccharide Binding Protein)		-60 to 180 minutes after first intervention (first high-fat meal), 0-180 minutes after second intervention (second high-fat meal)
Difference in concentration concentration of Cytokines		-60 to 180 minutes after first intervention (first high-fat meal), 0-180 minutes after second intervention (second high-fat meal)
Difference in concentration of apoB48		-60 to 180 minutes after first intervention (first high-fat meal), 0-180 minutes after second intervention (second high-fat meal)
Difference in concentration of apoB100		-60 to 180 minutes after first intervention (first high-fat meal), 0-180 minutes after second intervention (second high-fat meal)
Difference in glucose concentration	Continuous glucose monitoring (CGM)	-60 to 360 minutes after first intervention (first high-fat meal)
Difference in appetite sensation	Visual analogue scale (VAS)	-60 to 180 minutes after first intervention (first high-fat meal), 0-180 minutes after second intervention (second high-fat meal)
Difference in gastric emptying rate	Acetaminophen test	-60 to 180 minutes after first intervention (first high-fat meal), 0-180 minutes after second intervention (second high-fat meal)
Ad libitum meal test	Amount of food (in grams) intake at the end of the test day to measure if MFGM content and intactness influences ad libitum intake of calories at the next meal.	420 minutes after start of test day.
Metabolic rate	Indirect calorimetry	0-420 minutes
Substrate metabolism	Indirect calorimetry	0-420 minutes

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Arla Foods
• Investigators: Study Director: Esben Søndergaard, MD, PhD, Steno Diabetes Center Aarhus, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2024
• Primary Completion (Actual): December 1, 2024
• Study Completion (Actual): March 1, 2025

Study Registration Dates

• First Submitted: March 6, 2024
• First Submitted That Met QC Criteria: March 27, 2024
• First Posted (Actual): April 1, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 3, 2025
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Milk fat globule membrane
• Other Study ID Numbers: MFGM-FOR-HEALTH

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
• product manufactured in and exported from the U.S.: No