Long-Term Effects of Walnut Consumption on Brain Function

NCT07422220 | Not Yet Recruiting

• 1 other identifier: METC 25-018
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

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).

Conditions

Healthy; Brain Insulin Sensitivity; Cerebral Blood Flow; Brain Vascular Function; Satiety and Food Intake; Food Reward; Cognitive Performance; Abdominal Obesity; Cognitive Decline

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

Outcome Measures

Primary Outcomes (1)

• Cerebral blood flow (CBF) prior to and after application of intranasal insulin

  CBF will be non-invasively measured using the gold-standard methodology pseudo-continuous arterial spin labeling magnetic resonance imaging (pCASL MRI)

  From enrollment to the end of treatment at 24 weeks

Secondary Outcomes (2)

• 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

• Cognitive performance

  From enrollment to the end of treatment at 24 weeks.

Other Outcomes (27)

• Endothelial function - Flow Mediated Dilation

  From enrollment to the end of treatment at 24 weeks.

• Endothelial function - Carotid Artery Reactivity

  From enrollment to the end of treatment at 24 weeks.

• Markers related to arterial stiffness

  From enrollment to the end of the intervention at 24 weeks.

Study Arms (2)

Walnut

EXPERIMENTAL

Receive 50g walnuts per day

Dietary Supplement: Walnuts

Control

NO INTERVENTION

Does not receive walnuts and is supposed to refrain from nut consumption

Interventions

Walnuts DIETARY_SUPPLEMENT

24-week consumption of 50 g/day of walnuts as part of a healthy diet according to the Dutch dietary guidelines

Walnut

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Maastricht University Medical Center: lead
• California Walnut Commission: collaborator

Study Sites (1)

Maastricht University, Department of Nutrition and Movement Sciences

Maastricht, Limburg, 6200MD, Netherlands

Location

MeSH Terms

Conditions

Obesity, Abdominal; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Central Study Contacts

Peter J. Joris, PhD

CONTACT

+31883887250; p.joris@maastrichtuniversity.nl

Linda J. Kehr, MSc

CONTACT

+31433883931; linda.kehr@maastrichtuniversity.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2025
• First Posted: February 19, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: February 19, 2026

Record last verified: 2026-02

Locations

NL (1)