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NCT Number: NCT07422220

Long-Term Effects of Walnut Consumption on Brain Function

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).

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Key information

Conditions

Healthy Abdominal Obesity Body Weight Brain Insulin Sensitivity Brain Vascular Function Cerebral Blood Flow Cognition Disorders Cognitive Decline Cognitive Dysfunction Cognitive Performance Food Reward Mental Disorders Neurocognitive Disorders Nutrition Disorders Nutritional and Metabolic Diseases Obesity Obesity, Abdominal Overnutrition Overweight Pathological Conditions, Signs and Symptoms Satiety and Food Intake Signs and Symptoms

Age range

45 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Maastricht University, Department of Nutrition and Movement Sciences

Maastricht, Limburg, 6200MD, Netherlands

Location status: Recruiting

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

walnuts

Dietary Supplement

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

Primary outcomes

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

    Time frame: 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 outcomes

  1. Bloodoxygen level-dependent (BOLD) functional MRI (fMRI) activity to measure appetite-related brain reward activity

    Time frame: From enrollment to the end of treatment at 24 weeks

    BOLD fMRI activity will be measured before and while participants watch food pictures

  2. Cognitive performance

    Time frame: 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).

Other outcomes

  1. Endothelial function - Flow Mediated Dilation

    Time frame: From enrollment to the end of treatment at 24 weeks.

    Changes in diameter during Flow-Mediated Dilation (FMD) of the brachial artery will be assessed using ultrasound.

  2. Endothelial function - Carotid Artery Reactivity

    Time frame: From enrollment to the end of treatment at 24 weeks.

    Changes in diameter during Carotid Artery Reactivity (CAR) in response to a cold stressor will be assessed using ultrasound

  3. Markers related to arterial stiffness

    Time frame: From enrollment to the end of the intervention at 24 weeks.

    Pulse Wave Analysis (PWA) of the radial artery and Femoral-to-carotid Pulse Wave Velocity (PWV) in m/s will be measured with a tonometer using Sphygomocor

  4. Peripheral insulin sensitivity

    Time frame: From enrollment to the end of the intervention at 24 weeks.

    7-point oral glucose tolerance test (OGTT) to determine insulin sensitivity based on insulin and glucose concentrations, Matsuda index and 2h glucose tolerance (2h glucose concentrations)

  5. Brain perfusion

    Time frame: From enrollment to the end of treatment at 24 weeks.

    Cerebral blood flow velocity (CBFv) of the medial cerebral artery will be measured with transcranial Doppler ultrasound (TCD)

  6. Markers related to gut microbiota activity

    Time frame: From enrollment to the end of treatment at 24 weeks.

    Fecal and fasting plasma short-chain fatty acids (acetate, butyrate, propionate), fecal bile acids (cholic acid, chenodeoxycholic acid, doxycholic acid, lithocholic acid), fecal lipid (non-esterified fatty acids, triacylglycerides, total cholesterol)

  7. Perceived hunger and satiety

    Time frame: From enrollment to the end of treatment at 24 weeks.

    Visual analogue scales (VAS) questionnaires

  8. Mental health

    Time frame: From enrollment to the end of the intervention at 24 weeks.

    Beck Depression Inventory (BDI), State-Trait Anxiety Inventories (STAI)

  9. Mood

    Time frame: From enrollment to the end of the intervention at 24 weeks.

    Profile of Mood States (POMS) questionnaire

  10. Stress

    Time frame: From enrollment to the end of the intervention at 24 weeks.

    Perceived Stress Scale (PSS) questionnaire

  11. Sleep characteristics

    Time frame: From enrollment to the end of the intervention at 24 weeks.

    Pittsburgh Sleep Quality Index (PSQI) questionnaire to assess sleep duration, quality, latency, and efficiency

  12. Office blood pressure

    Time frame: From enrollment to the end of the intervention at 24 weeks.

    Office blood pressure and heart rate

  13. 24h ambulatory blood pressure

    Time frame: From enrollment to the end of the intervention at 24 weeks.

    24h ambulatory blood pressure measured every 15 min

  14. Lipid metabolism

    Time frame: From enrollment to the end of the intervention at 24 weeks"

    Circulating triacylglycerol, High-Density Lipoprotein (HDL) cholesterol, Low-Density Lipoprotein (LDL) cholesterol, and Total Cholesterol concentrations

  15. Markers related to low-grade systemic inflammation

    Time frame: From enrollment to the end of the intervention at 24 weeks.

    Interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)a, monocyte chemo attractant protein (MCP)-1, C-reactive protein (hsCRP) and serum amyloid A (SAA)

  16. Markers related to arterial stiffness

    Time frame: From enrollment to the end of the intervention at 24 weeks.

    Pulse Wave Velocity (PWV) in m/s measured with a tonometer using Sphygomocor

  17. Structural brain status

    Time frame: From enrollment to the end of the intervention at 24 weeks.

    High-resolution anatomical MPRAGE scan

  18. Body Composition - Fat Mass

    Time frame: From enrollment to the end of the intervention at 24 weeks.

    BodPod will be used to measure fat mass (weight)

  19. Body Composition - Fat Free Mass

    Time frame: From enrollment to the end of treatment at 24 weeks.

    BodPod will be used to measure fat free mass (weight).

  20. Ad libitum food intake - weight

    Time frame: From enrollment to the end of the intervention at 24 weeks.

    Ad libitum food intake (weight) in the fasted state

  21. Ad libitum food intake - Caloric content

    Time frame: From enrollment to the end of the intervention at 24 weeks.

    Ad libitum food intake (caloric content) in the fasted state.

  22. Satiety hormones related to food intake

    Time frame: From enrollment to the end of the intervention at 24 weeks.

    Plasma levels of GLP-1 before and after ad libitum food intake at time points 0, 15, 30, 60, 90 minutes.

  23. Retinal microvasculature

    Time frame: From enrollment to the end of the intervention at 24 weeks.

    Retinal microvascular calibers will be measured using retinal images made with a fundus camera

  24. Weight

    Time frame: From enrollment to the end of the intervention at 24 weeks.

    Weight in kilograms

  25. Waist circumference

    Time frame: From enrollment to the end of the intervention at 24 weeks.

    Waist circumference in centimeters

  26. Hip circumference

    Time frame: From enrollment to the end of the intervention at 24 weeks.

    Hip circumference in centimeters

  27. Food intake

    Time frame: From enrollment to the end of the intervention at 24 weeks.

    Food intake will be assessed using the Food Frequency Questionnaire

Interested in participating?

Recruiting

Interested in participating?

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Sponsors and collaborators

Lead sponsor

Maastricht University Medical Center

Other

Collaborators

  • California Walnut Commission

Registry information

Official study title

Long-Term Effects of Walnut Consumption on Brain Function in Men and Women With Abdominal Obesity

Acronym: WalBrain

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
Feb 19, 2026
Registry last updated
Jul 24, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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