An interventional study of Wild blueberry powder in Brain Insulin-sensitivity, Brain Vascular Function and Cerebral Blood Flow, sponsored by Maastricht University Medical Center. Recruiting at 1 site in Netherlands. Open to participants aged 60 Years to 75 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-09-17.
Sponsored by Maastricht University Medical Center · Not applicable, Interventional, and Prevention
Impaired brain vascular function precedes the development of reduced cognitive performance, while brain insulin-resistance is associated with cognitive decline. Evidence from epidemiological studies has already suggested beneficial effects of wild blueberry consumption on cognitive performance. However, underlying mechanisms have not yet been established, while well-controlled trials on longer-term effects of wild blueberries on cognitive performance are highly needed. This study hypothesizes that longer-term wild blueberry intake improves (regional) brain vascular function and insulin-sensitivity, thereby improving cognitive performance in older men and women. The primary objectives are to investigate in older adults the effect wild blueberry consumption on (regional) vascular function and insulin-sensitivity in the brain, and to focus on changes in cognitive performance as assessed with the CANTAB neuropsychological test battery (i.e., secondary objective). Cerebral blood flow responses before (brain vascular function) and after the administration of intranasal insulin spray (brain insulin-sensitivity) will be non-invasively quantified by the non-invasive gold standard magnetic resonance imaging (MRI)- perfusion method Arterial Spin Labeling (ASL).
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Adults will receive in a random order, freeze-dried wild blueberry powder or a matched placebo for sixteen weeks, with a wash-out period of minimal eight weeks in-between. The placebo is an appearance, taste and macronutrient, fiber and vitamin C-matched powder containing blueberry flavoring and aroma, coloring, glucose, fructose, citric acid, ascorbic acid, cellulose, fibersol-2, xanthin gum, pectin, and silica. The placebo does not contain any form of anthocyanin that could potentially interfere with the wild blueberry intervention.
The wild blueberry intervention consist of 100% freeze-dried wild blueberry powder, containing anthocyanins. Participants will consume daily 26 grams of freeze-dried wild blueberry powders for 16 weeks. Participants should consume the powders by mixing them with water once daily in the morning
Dietary Supplement: Wild blueberry powder
Study volunteers will consume daily 26 grams of wild blueberry powder for 16 weeks, which has to be dissolved in a glass of water.
MRI-brain perfusion measurement Arterial Spin Labeling
Cerebral blood flow responses before (brain vascular function) and after the administration of intranasal insulin (brain insulin-sensitivity) will be non-invasively quantified by MRI-perfusion method Arterial Spin Labeling (ASL).
Time frame: Change in brain perfusion at the end of a 16-week wild blueberry intervention and a 16-week control period with a matched placebo.
Cognitive performance measurement by Cambridge Neuropsychological Test Automated Battery
Cognitive performance will be investigated using Cambridge Neuropsychological Test Automated Battery (CANTAB), which will be performed on an Ipad. The cognitive task performance will be tested in three important cognitive domains namely attention, memory and executive function. Learning effects are prevented by randomization of the intervention periods and the settings of CANTAB, including parallel modes and stimuli randomization. The test will be performed in Dutch.
Time frame: Change in cognitive performance at the end of a 16-week wild blueberry intervention and a 16-week control period with a matched placebo.
Brain Insulin Sensitivity
Change in cerebral blood flow, as quantified non-invasively by the MRI perfusion method Arterial Spin Labeling (ASL), before and after application of intranasal insulin (160 IU).
Time frame: Change in outcomes at the end of a 16-week wild blueberry intervention and 16-week control period with a matched placebo.
Assessment of Glucose Metabolism by 7-Point OGTT
Glucose metabolism will be evaluated using a 7-point oral glucose tolerance test (OGTT). In this test, a participant drinks a glucose-containing solution, and blood samples are collected at seven time points (0', 15', 30', 45', 60', 90', 120') over two hours. Measuring glucose levels at seven different points provides a detailed picture of how the body processes and clears sugar from the blood, helping to identify early changes in insulin sensitivity and overall metabolic health.
Time frame: Change in glucose metabolism at the end of a 16-week wild blueberry intervention and a 16-week control period with a matched placebo.
Assessment of cardiovascular function by Flow-Mediated Vasodilation (FMD)
Vascular health will be assessed by flow-mediated vasodilation (FMD, expressed as %), a non-invasive ultrasound technique that measures how well a blood vessel widens in response to increased blood flow. By briefly restricting blood flow in the arm (by means of a cuff on the fore arm) and then releasing it, investigators can see how effectively the brachial artery relaxes and dilates. This response reflects the function of the endothelium, the inner lining of blood vessels, and is considered an important indicator of cardiovascular health. The percentage indicates the relative increase in the brachial diameter compared to its baseline size.
Time frame: Change in cardiovascular function at the end of a 16-week wild blueberry intervention and a 16-week control period with a matched placebo.
Assessment of cardiovascular function by Carotid Artery Reactivity (CAR)
The peripheral vascular function will be assessed by the carotid artery reactivity (CAR, expressed as %), a non-invasive technique that evaluates the ability of the carotid artery to dilate or constrict in response to specific physiological or pharmacological stimuli. The percentage indicates the relative change in the carotid artery's diameter compared to its baseline size. This method provides insight into endothelial function, vascular smooth muscle responsiveness, and overall arterial health, serving as an early marker for cardiovascular risk.
Time frame: Change in peripheral vascular function at the end of a 16-week wild blueberry intervention and a 16-week control period with a matched placebo.
Assessment of Arterial Stiffness by Pulse Wave Analysis (PWA)
Arterial stiffness and central blood pressure will be assessed by pulse wave analysis (PWA). This non-invasive method records the shape of the pulse wave generated by each heartbeat, from the wrist or arm. From this signal, central blood pressure is expressed in millimeters of mercury (mmHg), while derived indices of arterial stiffness (such as the augmentation index, AIx) are expressed in percentages (%), representing the relative contribution of reflected waves to the overall pulse wave. By analyzing how the wave travels and reflects in the arteries, investigators can gain insight into arterial elasticity, vascular resistance, and the overall condition of the cardiovascular system.
Time frame: Change in arterial stiffness at the end of a 16-week wild blueberry intervention and a 16-week control period with a matched placebo.
Assessment of arterial stiffness by Pulse Wave Velocity (PWV)
Arterial stiffness will be assessed by pulse wave velocity (PWV, expressed in meters per second \[m/s\]). This non-invasive technique measures the speed at which the pressure wave created by the heartbeat travels through the arteries. Since stiffer arteries allow the wave to move faster, PWV provides a reliable indicator of vascular elasticity and cardiovascular risk.
Time frame: Change in outcomes at the end of a 16-week wild blueberry intervention and a 16-week control period with a matched placebo.
Assessment of microvasculature by Retinal Microvascular Calibers
The microcirculation will be assessed by measuring retinal microvascular calibers. Using non-invasive retinal imaging, the diameters of small blood vessels in the back of the eye are quantified. Because the retina offers a unique 'window' to the body's microvascular system, changes in these tiny vessel widths can reveal early signs of vascular dysfunction and give an indication about cardiometabolic health.
Time frame: Change in outcomes at the end of a 16-week wild blueberry intervention and a 16-week control period with a matched placebo.
Measuring blood pressure using office and 24-hour ambulatory monitoring
Blood pressure (systolic and diastolic) and heart rate will be assessed through both office measurements and 24-hour ambulatory monitoring. Office blood pressure provides standardized readings taken in a clinical setting, while ambulatory blood pressure monitoring records values at regular intervals throughout the day (every 15 minutes) and night (every 30 minutes) as individuals go about their daily lives. Together, these methods give a more complete picture of blood pressure patterns, capturing variability, nighttime values, and potential masked or white-coat hypertension.
Time frame: Change in outcomes at the end of a 16-week wild blueberry intervention and a 16-week control period with a matched placebo.
Assessment of blood lipids: TAG, TC, and HDL-C
Blood lipid levels will be assessed by measuring triacylglycerol (TAG), total cholesterol (TC), and high-density lipoprotein cholesterol (HDL-C). These standard blood tests provide important information about fat metabolism and cardiovascular risk.
Time frame: Change in blood lipids at the end of a 16-week wild blueberry intervention and a 16-week control period with a matched placebo.
Assessment of blood glucose levels
Blood glucose will be measured from blood samples to determine the concentration of sugar in the bloodstream. Measuring blood glucose provides important information about metabolic health.
Time frame: Change in blood glucose levels at the end of a 16-week wild blueberry powder and a 16-week control period with a matched placebo.
Evaluation of metabolic function by insulin measurement
Insulin levels will be measured from blood samples to evaluate how the body regulates glucose. Measuring insulin provides insight into metabolic function and insulin sensitivity.
Time frame: Change in outcomes at the end of a 16-week wild blueberry intervention and 16-week control period with a matched placebo.
Metabolic risk markers - Low-grade systemic inflammation
Markers for low-grade systemic inflammation (IL-6,TNF-alfa) will be assessed in the blood plasma to determine low-grade systemic inflammation.
Time frame: Change in metabolic risk markers at the end of a 16-week wild blueberry intervention and 16-week control period with a matched placebo.
High-resolution structural brain imaging with MPRAGE
Brain structure will be assessed using a structural MRI with an MPRAGE sequence. This high-resolution imaging technique provides detailed pictures of brain anatomy, allowing investigators to examine the size and shape of different brain regions.
Time frame: Change in outcomes at the end of a 16-week wild blueberry intervention and 16-week control period with a matched placebo.
Single nucleotide polymorphism (SNPs)
Leucocytes will be isolated from EDTA blood. DNA will be isolated from these leucocytes according to standard procedures. DNA will be used for analyzing the presence of known SNPs in genes encoding proteins known to play a role in cholesterol metabolism.
Time frame: Change in outcomes at baseline measurements at the start of a 16-week wild blueberry intervention and a 16-week control period with a matched placebo.
Other perceivable benefits: Assessment of Quality of Life
Quality of life will be assessed using a 32-item questionnaire that covers multiple aspects of daily living and well-being. The questionnaire asks about physical health, emotional state, social relationships, and overall life satisfaction. By combining responses across these domains, it provides a broad picture of how individuals perceive and experience their quality of life.
Time frame: Change in outcomes at the end of a 16-week wild blueberry intervention and 16-week control period with a matched placebo.
Other perceivable benefits: assessment of sleep by the Pittsburgh Sleep Quality Index (PSQI)
Sleep characteristics will be assessed using the 10-item Pittsburgh Sleep Quality Index (PSQI). This standardized questionnaire asks about different aspects of sleep over the past month, including sleep duration, quality, and disturbances. By combining the responses, the PSQI provides an overall score that reflects both subjective sleep quality and potential sleep problems
Time frame: Change in sleep characteristics at the end of a 16-week wild blueberry intervention and 16-week control period with a matched placebo.
Other perceivable benefits: assessment of mood by the Affect Grid
Mood will be assessed using the Affect Grid, a simple self-report tool that measures two key dimensions of emotion: pleasure (ranging from positive to negative feelings) and arousal (ranging from calm to highly activated). Participants indicate their current state on a single-page grid, providing a quick and intuitive snapshot of their mood at that moment.
Time frame: Change in mood at the end of a 16-week wild blueberry intervention and 16-week control period with a matched placebo.
Other perceivable benefits: Assessment of Stress by the Perceived Stress Scale (PSS)
Stress will be assessed using the Perceived Stress Scale (PSS), a widely used questionnaire that asks about feelings and thoughts during the past month. The PSS captures how unpredictable, uncontrollable, and overloaded participants perceive their lives to be. Higher scores indicate greater levels of perceived stress, providing a useful measure of everyday psychological strain.
Time frame: Change in outcomes at the end of a 16-week wild blueberry intervention and 16-week control period with a matched placebo.
Weight
Weight will be determined in kilograms.
Time frame: At all test days (week 0, 8, 16, 24, 32, 40).
Length
Length will be determined in meters.
Time frame: At all test days (week 0, 8, 16, 24, 32, 40).
Waist circumference
Waist circumference in centimeters.
Time frame: At all test days (week 0, 8, 16, 24, 32, 40).
Hip circumference
Hip circumference in centimeters.
Time frame: At all test days (week 0, 8, 16, 24, 32, 40).
Assessment of food intake by Food Frequency Questionnaire (FFQ)
Food intake will be assessed using the Food Frequency Questionnaire (FFQ), a standardized dietary survey that asks participants how often they consume a wide range of foods and beverages in the past month. This method provides an overview of habitual dietary patterns, nutrient intake, and overall diet quality, making it a useful tool for linking nutrition with health outcomes.
Time frame: Change in food intake at the end of a 16-week wild blueberry intervention and 16-week control period with a matched placebo.
Assessment of cerebral perfusion by Transcranial Doppler Ultrasound (TCD)
Cerebral perfusion will be assessed using Transcranial Doppler ultrasound, a non-invasive method that measures blood flow in the middle cerebral artery. During the procedure, continuous blood flow velocity (CBFv) is recorded through the skull using ultrasound waves. This approach provides valuable information about the cerebrovascular health and function.
Time frame: Change in cerebral perfusion by TCD will be measured during baseline and at the end of 16-week intervention (wild blueberry) or placebo period.
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Maastricht University Medical Center