Alleviation Of Metabolic Endotoxemia In Adults With Metabolic Syndrome With Milk Fat Globule Membrane

NCT03860584 | Completed Results

• 1 other identifier: 2018H0564
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Metabolic syndrome (MetS) adults (n = 24; 18-65 y) will be enrolled to complete a 2-arm, double-blind, randomized controlled, crossover trial. They will be randomized in 4-unit blocks to receive, for 13 d, a controlled diet with dairy milk (3.5% fat; 3 servings/d) enriched with milk fat globule membrane (MFGM, MEB) or a matched dairy milk that instead contains soy lecithin/phospholipid (control, COMP). All foods during each study period will be provided to ensure weight maintenance and to increase homogeneity of gut and host responses. Anthropometrics and blood pressure will be assessed at days 0, 7, and 13. Prior to (day 0) and after each 2-wk arm (day 13), a fasting blood sample will be collected to assess serum endotoxin and metabolic chemistries (glucose, lipids, insulin), and Toll-like receptor 4 /nuclear factor kappaB (TLR4/NFκB)-dependent genes from whole blood. A breath sample will be collected to assess the correlation analysis of plasma metabolic biomarkers. After the 2-week intervention, from fecal samples collected on day 13, the investigators will assess microbiota composition and function, short chain fatty acids (SCFA), and intestinal inflammatory markers (calprotectin, myeloperoxidase). On d 13, participants in the fasted state will receive a high-fat/high-glucose meal challenge to induce gut-derived endotoxin translocation. At 30-minute intervals for 3-hour, the investigators will evaluate circulating endotoxin, glucose, and insulin; TLR4/NFκB-dependent genes will be assessed from whole blood at 0 hour and 3-hour. Gut permeability probes will be co-administered with the test meal challenge, and 24-hour urine will be collected to assess gut barrier integrity. Participants will then undergo a 2-week washout prior to receiving the alternative treatment and completing all procedures in an identical manner.

Conditions

Metabolic Syndrome; Metabolic Endotoxemia

Keywords

metabolic endotoxemia; milk fat globule membrane; gut health; endotoxin; inflammation; obesity

Outcome Measures

Primary Outcomes (2)

• Serum Endotoxin

  Data are biomarker fasting concentrations

  Day 13

• Serum Endotoxin

  Data are biomarker area under the time-concentration curve (0-3 hours) on day 13

  Day 13 (0, 30, 60, 90, 120, 150, 180 minutes post-meal challenge)

Secondary Outcomes (22)

• Plasma Glucose

  Day 13 (0, 30, 60, 90, 120, 150, 180 minutes post-meal challenge)

• Plasma Glucose

  Day 13

• Plasma Insulin

  Day 13

• Plasma Insulin

  day 13 (0, 30, 60, 90, 120, 150, 180 minutes post-meal challenge)

• Plasma HDL-C

  Day 13

Study Arms (2)

MFGM-enriched full-fat dairy milk

EXPERIMENTAL

Participants in this arm will receive MFGM-enriched full-fat dairy milk (3 servings/d) that contains MFGM at 10% phospholipid (relative to total lipid content) delivering MFGM at \~10-times that in full-fat dairy milk.

Dietary Supplement: MFGM-enriched full-fat dairy milk

Soy phospholipid/lecithin milk

PLACEBO COMPARATOR

Participants in this arm will receive a matched dairy milk that instead contains soy phospholipid/lecithin.

Dietary Supplement: Soy phospholipid/lecithin milk

Interventions

MFGM-enriched full-fat dairy milk DIETARY_SUPPLEMENT

MetS adults with metabolic endotoxemia will be enrolled to complete a 2-arm, double-blind, randomized controlled, crossover trial to test the independent benefits of MFGM. For each 2-wk arm, they will receive MFGM-enriched full-fat dairy milk (3 servings/d) or a matched dairy milk that instead contains soy phospholipid/lecithin (control). Milks have been formulated with soy lecithin or MFGM at 10% phospholipid (relative to total lipid content). This delivers MFGM at \~10-times that in full-fat dairy milk, which reflects that consumers obtain MFGM from dairy foods other than whole milk.

MFGM-enriched full-fat dairy milk

Soy phospholipid/lecithin milk DIETARY_SUPPLEMENT

MetS adults with metabolic endotoxemia will be enrolled to complete a 2-arm, double-blind, randomized controlled, crossover trial to test the independent benefits of MFGM. For each 2-wk arm, they will receive MFGM-enriched full-fat dairy milk (3 servings/d) or a matched dairy milk that instead contains soy phospholipid/lecithin (control). Milks have been formulated with soy lecithin or MFGM at 10% phospholipid (relative to total lipid content).

Soy phospholipid/lecithin milk

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Serum Glucose 100-126 mg/dl
• Waist C \>89/102 cm; F/M
• Serum HDL-C: \<50/40 mg/dl; F/M
• Serum triglyceride: \>150 mg/dl
• Blood Pressure \>130/85 mmHg

You may not qualify if:

• Unstable body mass (±2 kg over prior 3-mo)
• Vegetarian
• Food allergies or lactose intolerance
• User of dietary supplements or probiotics (within past 1-mo)
• Pregnancy, lactation, changes in birth control (within 6-mo)
• Any gastrointestinal disorders
• Chronic diarrhea
• Smoker
• Excess alcohol (\>2 drinks/d)
• Excess aerobic exercise (\>5 h/wk)
• Recent antibiotic or anti-inflammatory agent use
• Blood Pressure \>140/90 mmHg

Sponsors & Collaborators

• Ohio State University: lead

Study Sites (1)

The Ohio State University

Columbus, Ohio, 43201, United States

Location

Related Publications (4)

• Pokala A, Kraft J, Taormina VM, Michalski MC, Vors C, Torres-Gonzalez M, Bruno RS. Whole milk dairy foods and cardiometabolic health: dairy fat and beyond. Nutr Res. 2024 Jun;126:99-122. doi: 10.1016/j.nutres.2024.03.010. Epub 2024 Mar 21.

  PMID: 38669850 BACKGROUND

• Bruno RS, Pokala A, Torres-Gonzalez M, Blesso CN. Cardiometabolic health benefits of dairy-milk polar lipids. Nutr Rev. 2021 Dec 8;79(Suppl 2):16-35. doi: 10.1093/nutrit/nuab085.

  PMID: 34879146 BACKGROUND

• Quarles WR, Pokala A, Shaw EL, Ortega-Anaya J, Hillmann L, Jimenez-Flores R, Bruno RS. Alleviation of Metabolic Endotoxemia by Milk Fat Globule Membrane: Rationale, Design, and Methods of a Double-Blind, Randomized, Controlled, Crossover Dietary Intervention in Adults with Metabolic Syndrome. Curr Dev Nutr. 2020 Jul 25;4(9):nzaa130. doi: 10.1093/cdn/nzaa130. eCollection 2020 Sep.

  PMID: 32885133 BACKGROUND

• Pokala A, Quarles WR, Ortega-Anaya J, Jimenez-Flores R, Cao S, Zeng M, Hodges JK, Bruno RS. Milk-Fat-Globule-Membrane-Enriched Dairy Milk Compared with a Soy-Lecithin-Enriched Beverage Did Not Adversely Affect Endotoxemia or Biomarkers of Gut Barrier Function and Cardiometabolic Risk in Adults with Metabolic Syndrome: A Randomized Controlled Crossover Trial. Nutrients. 2023 Jul 23;15(14):3259. doi: 10.3390/nu15143259.

  PMID: 37513677 RESULT

MeSH Terms

Conditions

Metabolic Syndrome; Inflammation; Obesity

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms

Results Point of Contact

• Title: Richard Bruno
• Organization: Ohio State University

bruno.27@osu.edu

8603358494

Study Officials

• Richard Bruno, PhD

  Ohio State University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Both participants and key research personnel will be blinded between MFGM-enriched full-fat dairy milk (treatment) and milk with soy phospholipid/lecithin (control).
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Principal Investigator

Model Details: 2-arm, double-blind, randomized controlled, crossover trial

Study Record Dates

• First Submitted: February 28, 2019
• First Posted: March 4, 2019
• Study Start: July 1, 2019
• Primary Completion: December 20, 2020
• Study Completion: December 20, 2020
• Last Updated: November 18, 2025
• Results First Posted: September 24, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)