Overview

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).

Eligibility

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)