High-Dairy Food Patterns and Gut-Brain Axis

NCT07355309 | Not Yet Recruiting

• 1 other identifier: METC25-043
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Disturbances in brain insulin sensitivity are associated not only with obesity and type 2 diabetes, but also with brain aging and cognitive decline. Longitudinal studies suggest that dietary patterns, particularly those high in dairy intake, may impact brain function via the gut-brain axis. Indeed, dairy foods are known to modulate gut microbiota and may, through this pathway, not only improve brain insulin sensitivity and cognitive performance, but also mental health and appetite regulation. However, underlying mechanisms remain largely unexplored. The primary objective of this study is to evaluate, in older adults with overweight or obesity, the effects of a high-dairy food pattern (4-5 daily servings of (butter)milk, cheese, yogurt, or cottage cheese) compared to a low-dairy food pattern (≤1 serving daily) on (regional) brain vascular function and insulin sensitivity. These outcomes will be quantified using the non-invasive MRI perfusion technique Arterial Spin Labeling (ASL), which assesses cerebral blood flow (CBF) in response to intranasal insulin, a validated physiological marker of brain insulin sensitivity. Secondary objectives include changes in cognitive performance (via the CANTAB neuropsychological test battery), gut microbiota composition (via shotgun metagenomic analysis of fecal samples), and appetite-related brain reward activity (via BOLD-fMRI with food cues). Exploratory analyses include conventional cardiometabolic risk markers (blood pressure, lipid and glucose metabolism), and perceivable (consumer) benefits.

Conditions

Brain Insulin Sensitivity; Brain Vascular Function; Cerebral Blood Flow; Cognitive Performance; Appetite Control; Gut Microbiota

Outcome Measures

Primary Outcomes (2)

• Brain Insulin Sensitivity

  Cerebral blood flow measurements before and after a nasal insulin spray as quantified non-invasively by the MRI perfusion method Arterial Spin Labeling (ASL)

  Change in brain insulin sensitivity (difference in CBF [mL/100 g tissue/min] before and after intranasal insulin) at the end of an 8-week high-dairy food pattern and an 8-week low-dairy food pattern

• Brain vascular function

  Cerebral blood flow as quantified non-invasively by the MRI perfusion method Arterial Spin Labeling (ASL)

  Change in brain vascular function (CBF in mL/100 g tissue/min) at the end of an 8-week high-dairy food pattern and an 8-week low-dairy food pattern

Secondary Outcomes (3)

• Cognitive Performance

  Change in cognitive performance (test-specific standardized scores) at the end of an 8-week high-dairy food pattern and an 8-week low-dairy food pattern

• Gut microbial composition

  Change in gut microbial composition (shannon index indicating α-diversity) using gene relative abundance profiles at the start and end of an 8-week high-dairy food pattern and an 8-week low-dairy food pattern

• Appetite-related brain reward activity

  Change in appetite-related brain reward activity (functional connectivity [BOLD signal changes]) at the end of an 8-week high-dairy food pattern and an 8-week low-dairy food pattern

Other Outcomes (18)

• Office blood pressure

  Change in blood pressure (in mmHg) at the end of an 8-week high-dairy food pattern and an 8-week low-dairy food pattern

• Heart rate

  Change in heart rate (in beats/min) at the end of an 8-week high-dairy food pattern and an 8-week low-dairy food pattern

• Glucose concentrations

  Change in circulating glucose concentrations (in mmol/L) at the end of an 8-week high-dairy food pattern and an 8-week low-dairy food pattern

Study Arms (2)

Experimental

EXPERIMENTAL

High-Dairy Food Pattern

Dietary Supplement: High-dairy food pattern

Control

PLACEBO COMPARATOR

Low-Dairy Food Pattern

Dietary Supplement: Low-dairy food pattern

Interventions

High-dairy food pattern DIETARY_SUPPLEMENT

During the high-dairy period, participants will be instructed to consume 4-5 daily servings of dairy products, including: 1-2 servings of yogurt or cottage cheese (200 mL per serving, ≤1.5% fat), 1-2 servings of milk or buttermilk (250 mL per serving, ≤1.5% fat), and 1-2 servings of cheese (20 g per serving, 20+ or 30+ reduced-fat options).

Experimental

Low-dairy food pattern DIETARY_SUPPLEMENT

During the low-dairy control period, participants will restrict dairy intake to a maximum of one serving per day

Control

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and postmenopausal women (≥ 2 years since last menstruation);
• Aged between 40-75 years;
• BMI between 25-35 kg/m2 (overweight or obese);
• Low-to-moderate habitual dairy consumption (≤ 3 servings/day);
• Fasting serum total cholesterol \< 8.0 mmol/L;
• Fasting serum triacylglycerol \< 4.5 mmol/L;
• Fasting plasma glucose \< 7.0 mmol/L;
• Systolic blood pressure \< 160 mmHg and diastolic blood pressure \< 100 mmHg;
• Stable body weight (weight gain or loss \< 3 kg in the past three months).

You may not qualify if:

• Left-handedness;
• Milk protein allergy or lactose intolerance;
• Current smoker, or smoking cessation \< 12 months;
• Familial hypercholesterolemia;
• Abuse of drugs;
• Alcoholic intake \>3 standard drinks/day;
• Use of medications, food products or dietary supplements affecting glucose, lipid, or blood pressure regulation, gut microbiota or mental or neurological function, judged by the principal investigator;
• Use of antibiotics within the previous month;
• Use of other biomedical investigational products within the previous month;
• Participation in another clinical trial within the past month;
• Severe medical conditions including type 2 diabetes, epilepsy, asthma, kidney failure, COPD, inflammatory bowel disease, autoimmune diseases, or rheumatoid arthritis;
• History of cardiovascular events (e.g., heart attack, stroke) or active cardiovascular disease;
• Contra-indications for MRI imaging (e.g. pacemaker, metal implants, claustrophobia);
• Difficult to venipuncture as evidenced during the screening visit.

Sponsors & Collaborators

• Maastricht University Medical Center: lead
• National Dairy Council: collaborator

Study Sites (1)

Maastricht University

Maastricht, Limburg, 6229ER, Netherlands

Location

Study Officials

• Ronald P Mensink, PhD

  Maastricht University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kevin MR Nijssen, PhD

CONTACT

+31433881305; k.nijssen@maastrichtuniversity.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study is a randomized, controlled, crossover intervention trial. Each participant will complete two 8-week intervention periods (high-dairy and low-dairy food patterns) separated by a washout period of at least 8 weeks, resulting in a total study duration of approximately 24 weeks.

Study Record Dates

• First Submitted: December 10, 2025
• First Posted: January 21, 2026
• Study Start: December 22, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: January 21, 2026

Record last verified: 2026-01

Locations

NL (1)