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.
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);
Left-handedness;
Milk protein allergy or lactose intolerance;
Current smoker, or smoking cessation < 12 months;
Familial hypercholesterolemia;
Crossover
High-dairy food pattern
Dietary supplementDuring 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 supplementDuring the low-dairy control period, participants will restrict dairy intake to a maximum of one serving per day
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)
Brain vascular function
Cerebral blood flow as quantified non-invasively by the MRI perfusion method Arterial Spin Labeling (ASL)
Cognitive Performance
Cambridge Neuropsychological Test Automated Battery (CANTAB)
Gut microbial composition
Shotgun metagenomics of fecal samples
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
Office blood pressure
Office blood pressure
Heart rate
Heart rate
Glucose concentrations
Circulating glucose concentrations
Insulin concentrations
Circulating insulin concentrations
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Maastricht University Medical Center
Lead sponsor
National Dairy Council
Collaborator
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