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Completed

NCT Number: NCT07429903

Effect of Daily Walnut Consumption on Memory in Subjects With Long-COVID

Approximately 30% of patients experience "Long-COVID" syndrome presenting with symptoms such as cognitive difficulties ('brain fog'), fatigue, dyspnea, autonomic dysfunction, depression and anxiety, lasting beyond 12 weeks causing significant disability, and threaten health and wellbeing of millions around the world. At the current time, there is no effective treatment for long-COVID. Walnuts contain a mixture of nutrients and phytochemicals include monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), and alpha-linolenic acid (ALA). Walnut consumption was directly associated with cognitive function. The investigators have shown pomegranate that share the same phytonutrient ellagitannins as walnut and mixed nuts including walnuts could increase blood microbiome metabolites of tryptophan metabolite indole propionate and serotonin levels via change of gut microbiota and therefore play an essential role in gut-brain axis including cognitive function. The proposed pilot study will include 76 adults (ages >40 years) with diagnosis of SARS-CoV2 infection presenting with long-COVID symptoms lasting longer than 12 weeks. They will be randomized 1:1 to usual care vs. an intervention group that will include 2 oz (57g) of walnuts daily into their habitual diet for 12 weeks. The investigators will compare the improvement in symptoms of cognitive complains of "brain fog", fatigue and depression of the active intervention group vs. usual care. The outcome of the investigation of the benefit of walnut consumption will provide important novel information on using dietary sources of polyunsaturated fatty acids and phytochemicals to mitigate the common symptoms of long-COVID. This application was submitted in response to the California Walnut Commission's commodity board topic.

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Key information

Conditions

Long-COVID Behavior Behavioral Symptoms Brain Fog COVID-19 Chronic Disease Cognition Coronaviridae Infections Coronavirus Infections Disease Attributes Fatigue Infections Lung Diseases Memory Mental Fatigue Nidovirales Infections Pathologic Processes Pathological Conditions, Signs and Symptoms Pneumonia Pneumonia, Viral Post-Acute COVID-19 Syndrome Post-Infectious Disorders RNA Virus Infections Respiratory Tract Diseases Respiratory Tract Infections Signs and Symptoms Virus Diseases

Age range

40 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

UCLA Center for Human Nutrition

Los Angeles, California, 90025, United States

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

Age 40 years and older

History of confirmed SARS-CoV-2 infection

Presence of long-COVID symptoms lasting longer than 12 weeks, including one or more of the following:

  • Cognitive complaints ("brain fog," memory, attention, or processing speed difficulties)
  • Fatigue
  • Mood symptoms (e.g., depression)

Consumption of a low-polyphenol (Western) diet

Adequate visual acuity and hearing to complete neuropsychological testing

Screening laboratory results without clinically significant abnormalities that would interfere with study participation

Ability and willingness to provide written informed consent

Exclusion criteria

Diagnosis of probable Alzheimer's disease or other dementia (e.g., vascular, Lewy body, frontotemporal)

Other neurological or medical conditions that may cause cognitive impairment

Evidence of Parkinson's disease based on motor examination

Uncontrolled hypertension (systolic BP >170 mmHg or diastolic BP >100 mmHg)

Allergy to walnuts

Regular consumption of more than 5 oz of walnuts per week

Current diagnosis of a major psychiatric disorder according to DSM-5 criteria

Alcoholism or substance use disorder

Any condition that, in the investigator's judgment, would make participation unsafe or interfere with study completion

Treatment and study plan

whole food - walnuts

Other

Participants randomized to the intervention group will consume (2 oz ) of whole walnuts daily, incorporated into their diet for 12 weeks. Walnuts were provided to participants, and adherence was monitored using dietary records.

Primary outcomes

  1. Episodic Memory - RAVLT-Revised Long-Delay Free Recall (number of words recalled)

    Time frame: Baseline to Week 12

    Change in long-delay free recall score (number of words correctly recalled) on the RAVLT-Revised from baseline to week 12.

Secondary outcomes

  1. Executive Function

    Time frame: Baseline to Week 12

    Digit Vigilance Test Score Description: Total completion time (seconds) and/or number of errors on the Digit Vigilance Test, assessing sustained attention and processing speed.

  2. Trail Making Test Part A Completion Time

    Time frame: baseline and 12 weeks

    Description: Time to completion (seconds) for Trail Making Test Part A, assessing processing speed.

  3. Fatigue

    Time frame: Baseline and 12

    Patient-Reported Outcomes Measurement Information System (PROMIS®) Fatigue Short Form - 8 Item.

    Fatigue will be assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS®) Fatigue Short Form (8 items). Raw scores range from 8 to 40, with higher scores indicating greater fatigue (worse outcome). Scores may also be converted to standardized T-scores (mean = 50, SD = 10), where higher T-scores indicate greater fatigue.

  4. Mood

    Time frame: baseline and 12 weeks

    PROMIS® Depression Short Form (8 items)

  5. NIH Toolbox Cognitive Battery (NIHTB-CB) - Fluid Intelligence Composite

    Time frame: Baseline to Week 12

    Fluid cognitive function will be assessed using the Fluid Intelligence Composite score from the NIH Toolbox Cognitive Battery. The composite is a standardized score (mean = 100, SD = 15), with higher scores indicating better cognitive performance.

  6. Quality of Life

    Time frame: Baseline and 12

    SF-36 Health Survey

  7. Blood Pressure

    Time frame: Baseline and Week 12

    Seated systolic and diastolic blood pressure

    Systolic and diastolic blood pressure will be measured in millimeters of mercury (mmHg) using an automated calibrated sphygmomanometer after 5 minutes of seated rest. Higher values indicate higher blood pressure.

  8. Dietary Intake

    Time frame: Baseline and 12

    24-hour dietary recall (ASA24™)

  9. Blood and Urine Biomarkers

    Time frame: Baseline, 12 Weeks

    Measures:

    metabolic markers and inflammatory Blood fatty acid profile Plasma ellagic acid Urinary urolithin metabolites (LC-MS/MS)

  10. WAIS-IV Symbol Search Score

    Time frame: Baseline and 12 weeks

    Total correct responses (scaled score) on the WAIS-IV Symbol Search subtest, assessing processing speed.

  11. Heart Rate

    Time frame: Baseline and Week 12

    Resting heart rate

    Description:

    Resting heart rate will be measured in beats per minute (bpm) using an automated blood pressure monitor after 5 minutes of seated rest.

  12. Body Weight

    Time frame: baseline and week 12

    Measure:

    Body weight in kilograms

    Description:

    Body weight will be measured in kilograms (kg) using a calibrated digital scale with participants wearing light clothing and no shoes.

Sponsors and collaborators

Lead sponsor

University of California, Los Angeles

Other

Registry information

Important dates

Study start
2023
Primary completion
2025
Study completion
2025
First posted
Feb 24, 2026
Registry last updated
Feb 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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