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NCT Number: NCT07355309

High-Dairy Food Patterns and Gut-Brain Axis

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.

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Key information

Age range

40 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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).

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

Primary outcomes

  1. Brain Insulin Sensitivity

    Time frame: 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

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

  2. Brain vascular function

    Time frame: 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

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

Secondary outcomes

  1. Cognitive Performance

    Time frame: 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

    Cambridge Neuropsychological Test Automated Battery (CANTAB)

  2. Gut microbial composition

    Time frame: 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

    Shotgun metagenomics of fecal samples

  3. Appetite-related brain reward activity

    Time frame: 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

    Appetite-related brain reward activity will be assessed by blood oxygenation level-dependent (BOLD) functional MRI responses to standardized food cues

Other outcomes

  1. Office blood pressure

    Time frame: 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

    Office blood pressure

  2. Heart rate

    Time frame: 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

    Heart rate

  3. Glucose concentrations

    Time frame: 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

    Circulating glucose concentrations

  4. Insulin concentrations

    Time frame: 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

    Circulating insulin concentrations

  5. Lipid metabolism

    Time frame: 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

    Circulating lipid concentrations

  6. Markers related to low-grade systemic inflammation

    Time frame: 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

    Circulating high-sensitive C-reactive protein concentrations

  7. Perceived hunger

    Time frame: 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

    Visual analogue scale (VAS) questionnaires for hunger

  8. Perceived satiety

    Time frame: 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

    Visual analogue scale (VAS) questionnaires for satiety

  9. Perceived desire to eat

    Time frame: 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

    Visual analogue scale (VAS) questionnaires for desire to eat

  10. Perceived fullness

    Time frame: 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

    Visual analogue scale (VAS) questionnaires for fullness

  11. Perceived quality of life

    Time frame: 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

    32-item quality of life questionnaire to assess perceived quality of life

  12. Perceived mood

    Time frame: 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

    Affect Grid Questionnaire to assess perceived mood

  13. Perceived depression and anxiety symptoms

    Time frame: 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

    Beck Depression and Anxiety Inventories to assess perceived depression and anxiety symptoms

  14. Perceived stress

    Time frame: 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 Stress Scale questionnaire to assess perceived stress

  15. Perceived sleep quality

    Time frame: 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

    Pittsburgh Sleep Quality Index to assess perceived sleep quality

  16. Food intake

    Time frame: Change in food intake at the end of an 8-week high-dairy food pattern and an 8-week low-dairy food pattern

    Food Frequency Questionnaire to assess food intake over the past month

  17. Urinary calcium

    Time frame: 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

    24-hour urine samples for analysis of calcium concentrations

  18. Urinary urea

    Time frame: 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

    24-hour urine samples for analysis of urea concentrations

Study contacts

Contact information is provided by the study sponsor or research team.

Kevin MR Nijssen, PhD

CONTACT

[email protected]

+31433881305

Sponsors and collaborators

Lead sponsor

Maastricht University Medical Center

Other

Collaborators

  • National Dairy Council

Registry information

Official study title

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

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
Jan 21, 2026
Registry last updated
Jan 21, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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