High-Dairy Food Patterns and Gut-Brain Axis

Longer-term Effects of High-dairy Food Patterns on the Gut-brain Axis in Adults With Overweight or Obesity

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Cerebral Blood Flow; Cognitive Performance; Gut Microbiota; Appetite Control; Brain Vascular Function; Brain Insulin Sensitivity
• Intervention / Treatment: Dietary supplement: High-dairy food pattern; Dietary supplement: Low-dairy food pattern

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kevin MR Nijssen, PhD; Phone Number: +31433881305; Email: k.nijssen@maastrichtuniversity.nl

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6229ER
      • Maastricht University
      • Contact: Kevin MR Nijssen, PhD; Phone Number: +3143 3881305; Email: k.nijssen@maastrichtuniversity.nl

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 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).

Exclusion Criteria:

• 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);
• Willing to donate blood starting from 8 weeks before the study begins, throughout the study, and for 4 weeks after its inclusion;
• Difficult to venipuncture as evidenced during the screening visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental; High-Dairy Food Pattern	Dietary supplement: High-dairy food pattern; 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).
Placebo Comparator: Control; Low-Dairy Food Pattern	Dietary supplement: Low-dairy food pattern; During the low-dairy control period, participants will restrict dairy intake to a maximum of one serving per day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive Performance	Cambridge Neuropsychological Test Automated Battery (CANTAB)	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	Shotgun metagenomics of fecal samples	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	Appetite-related brain reward activity will be assessed by blood oxygenation level-dependent (BOLD) functional MRI responses to standardized food cues	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Office blood pressure	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	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	Circulating 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
Insulin concentrations	Circulating insulin concentrations	Change in insulin concentrations (in mIU/L) at the end of an 8-week high-dairy food pattern and an 8-week low-dairy food pattern
Lipid metabolism	Circulating lipid concentrations	Change in circulating lipid concentrations (in mmol/L) at the end of an 8-week high-dairy food pattern and an 8-week low-dairy food pattern
Markers related to low-grade systemic inflammation	Circulating high-sensitive C-reactive protein concentrations	Change in circulating high-sensitive C-reactive protein concentrations (in mg/dl) at the end of an 8-week high-dairy food pattern and an 8-week low-dairy food pattern
Perceived hunger	Visual analogue scale (VAS) questionnaires for hunger	Change in perceived hunger (in mm) at the end of an 8-week high-dairy food pattern and an 8-week low-dairy food pattern
Perceived satiety	Visual analogue scale (VAS) questionnaires for satiety	Change in perceived satiety (in mm) at the end of an 8-week high-dairy food pattern and an 8-week low-dairy food pattern
Perceived desire to eat	Visual analogue scale (VAS) questionnaires for desire to eat	Change in perceived desire to eat (in mm) at the end of an 8-week high-dairy food pattern and an 8-week low-dairy food pattern
Perceived fullness	Visual analogue scale (VAS) questionnaires for fullness	Change in perceived fullness (in mm) at the end of an 8-week high-dairy food pattern and an 8-week low-dairy food pattern
Perceived quality of life	32-item quality of life questionnaire to assess perceived quality of life	Change in perceived quality of life (average score) at the end of an 8-week high-dairy food pattern and an 8-week low-dairy food pattern
Perceived mood	Affect Grid Questionnaire to assess perceived mood	Change in perceived mood (average score) at the end of an 8-week high-dairy food pattern and an 8-week low-dairy food pattern
Perceived depression and anxiety symptoms	Beck Depression and Anxiety Inventories to assess perceived depression and anxiety symptoms	Change in perceived depression and anxiety symptoms (average scores) at the end of an 8-week high-dairy food pattern and an 8-week low-dairy food pattern
Perceived stress	Perceived Stress Scale questionnaire to assess perceived stress	Change in perceived stress (average score) at the end of an 8-week high-dairy food pattern and an 8-week low-dairy food pattern
Perceived sleep quality	Pittsburgh Sleep Quality Index to assess perceived sleep quality	Change in perceived sleep quality (average score) at the end of an 8-week high-dairy food pattern and an 8-week low-dairy food pattern
Food intake	Food Frequency Questionnaire to assess food intake over the past month	Change in food intake at the end of an 8-week high-dairy food pattern and an 8-week low-dairy food pattern
Urinary calcium	24-hour urine samples for analysis of calcium concentrations	Change in urinary calcium (mmol/24 hours) at the start and end of an 8-week high-dairy food pattern and an 8-week low-dairy food pattern
Urinary urea	24-hour urine samples for analysis of urea concentrations	Change in urinary urea (mmol/24 hours) at the start and end of an 8-week high-dairy food pattern and an 8-week low-dairy food pattern

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Collaborators: National Dairy Council
• Investigators: Principal Investigator: Ronald P Mensink, PhD, Maastricht University

Study record dates

Study Major Dates

• Study Start (Estimated): December 22, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: December 10, 2025
• First Submitted That Met QC Criteria: January 12, 2026
• First Posted (Actual): January 21, 2026

Study Record Updates

• Last Update Posted (Actual): January 21, 2026
• Last Update Submitted That Met QC Criteria: January 12, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: METC25-043

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No