Healthy, Brain Insulin Sensitivity, Cerebral Blood Flow, Brain Vascular Function, Satiety and Food Intake, Food Reward, Cognitive Performance, Abdominal Obesity, Cognitive Decline
Conditions
Keywords
Walnuts, Juglans, Brain vascular function, Brain insulin sensitivity, Satiety, Food reward mechanisms, Cognitive performance, Abdominal obesity, Cognitive decline, pCASL MRI, fMRI, CANTAB, Intranasal insulin, Food cues
Brief summary
Rationale: Healthy foods, including mixed nuts, may improve brain function, which is essential for cognitive and metabolic health, and may contribute to improved food intake regulation. It is therefore important to investigate the specific effects of walnuts on cerebral blood flow responses before and after intranasal insulin administration, as well as their associated functional benefits. The investigators hypothesize that long-term walnut consumption improves vascular function and insulin-sensitivity in the brain, thereby enhancing cognitive performance and appetite control in abdominally obese men and women. Objective: The primary objectives are to investigate in abdominally obese adults the effects of 24-week walnut consumption on (regional) vascular function and insulin-sensitivity in the brain, while the investigators will also assess changes in cognitive performance and appetite-related brain reward activity (secondary objectives). Cerebral blood flow responses before (brain vascular function) and after the administration of intranasal insulin spray (brain insulin-sensitivity) will be quantified by the non-invasive gold standard magnetic resonance imaging (MRI)-perfusion method Arterial Spin Labeling (ASL). Study design: This intervention study will have a randomized, controlled parallel design. The total study duration will be 24 weeks. Study population: Fifty-five abdominally obese men and (postmenopausal) women (aged 45-75 years) without a history of cardiovascular diseases or complaints will participate. This study population is expected to have a decreased cerebral blood flow at baseline and are also at increased risk of cognitive impairment, allowing for improvement by the intervention. Intervention: Study participants will receive daily 50 g (about 15% of energy) of raw walnuts (walnut intervention) or no walnuts (control intervention) for 24 weeks. Main study parameters/endpoints: At baseline and after 24 weeks (follow-up), participants will visit the research facilities for assessments. The primary endpoint is the difference in the cerebral blood flow response before and after intranasal insulin administration between the walnut and control intervention. Cognitive performance will be assessed, while the investigators will also focus on appetite-related brain reward activity (secondary outcomes).
Interventions
DIETARY_SUPPLEMENTWalnuts
24-week consumption of 50 g/day of walnuts as part of a healthy diet according to the Dutch dietary guidelines
Sponsors
Maastricht University Medical Center
California Walnut Commission
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
45 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Men and women, aged between 45-75 years * Women postmenopausal: two or more years after last menstruation * Waist circumference of ≥102 cm for men and ≥88 cm for women (abdominal obesity) * Fasting plasma glucose \< 7.0 mmol/L * Fasting serum total cholesterol \< 8.0 mmol/L * Fasting serum triacylglycerol \< 4.5 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) * Willingness to give up being a blood donor from 8 weeks before the start of the study, during the study and for 4 weeks after completion of the study * No difficult venipuncture as evidenced during the screening visit
Exclusion criteria
* Allergy or intolerance to walnuts * Left-handedness (effects on brain function differ between left- and right-handed adults) * Current smoker, or smoking cessation \< 12 months * Diabetic patients * Familial hypercholesterolemia * Abuse of drugs * More than 3 alcoholic consumptions per day * Use of products or dietary supplements (e.g., dietary fiber or antioxidant dietary supplements (vitamin C and E), fish or seaweed oil capsules) known to interfere with the main outcomes as judged by the principal investigators * Use of medication to treat blood pressure, lipid, or glucose metabolism * Use of an investigational product within another biomedical intervention trial within the previous 1-month * Severe medical conditions that might interfere with the study, such as epilepsy, asthma, kidney failure or renal insufficiency, chronic obstructive pulmonary disease, inflammatory bowel diseases, auto inflammatory diseases, and rheumatoid arthritis * Active cardiovascular disease like congestive heart failure or cardiovascular event, such as an acute myocardial infarction or cerebrovascular accident * Contra-indications for MRI imaging (e.g., pacemaker, surgical clips/material in body, metal splinter in eye, claustrophobia)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cerebral blood flow (CBF) prior to and after application of intranasal insulin | From enrollment to the end of treatment at 24 weeks | CBF will be non-invasively measured using the gold-standard methodology pseudo-continuous arterial spin labeling magnetic resonance imaging (pCASL MRI) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bloodoxygen level-dependent (BOLD) functional MRI (fMRI) activity to measure appetite-related brain reward activity | From enrollment to the end of treatment at 24 weeks | BOLD fMRI activity will be measured before and while participants watch food pictures |
| Cognitive performance | From enrollment to the end of treatment at 24 weeks. | Cognitive performance measurement of the following cognitive domains: memory, executive function and psychomotor speed. Measurements will be performed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). |
Countries
Netherlands
Contacts
CONTACTPeter J. Joris, PhD
CONTACTLinda J. Kehr, MSc
Outcome results
None listed