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.

Study Overview

• Status: Completed
• Conditions: Cognition; Memory; Long-COVID; Brain Fog
• Intervention / Treatment: Other: whole food - walnuts

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90025
      • UCLA Center for Human Nutrition

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Walnuts	Other: whole food - walnuts; 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.
No Intervention: Control; Habitual diet while avoiding nuts

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Episodic Memory - RAVLT-Revised Long-Delay Free Recall (number of words recalled)	Change in long-delay free recall score (number of words correctly recalled) on the RAVLT-Revised from baseline to week 12.	Baseline to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Executive Function	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.	Baseline to Week 12
Trail Making Test Part A Completion Time	Description: Time to completion (seconds) for Trail Making Test Part A, assessing processing speed.	baseline and 12 weeks
Fatigue	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.	Baseline and 12
Mood	PROMIS® Depression Short Form (8 items)	baseline and 12 weeks
NIH Toolbox Cognitive Battery (NIHTB-CB) - Fluid Intelligence Composite	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.	Baseline to Week 12
Quality of Life	SF-36 Health Survey	Baseline and 12
Blood Pressure	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.	Baseline and Week 12
Dietary Intake	24-hour dietary recall (ASA24™)	Baseline and 12
Blood and Urine Biomarkers	Measures: metabolic markers and inflammatory Blood fatty acid profile Plasma ellagic acid Urinary urolithin metabolites (LC-MS/MS)	Baseline, 12 Weeks
WAIS-IV Symbol Search Score	Total correct responses (scaled score) on the WAIS-IV Symbol Search subtest, assessing processing speed.	Baseline and 12 weeks
Heart Rate	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.	Baseline and Week 12
Body Weight	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.	baseline and week 12

Collaborators and Investigators

• Sponsor: University of California, Los Angeles

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2023
• Primary Completion (Actual): January 24, 2025
• Study Completion (Actual): January 24, 2025

Study Registration Dates

• First Submitted: January 23, 2026
• First Submitted That Met QC Criteria: February 17, 2026
• First Posted (Actual): February 24, 2026

Study Record Updates

• Last Update Posted (Actual): February 24, 2026
• Last Update Submitted That Met QC Criteria: February 17, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Post-Infectious Disorders; COVID-19; Pathologic Processes; Chronic Disease; Disease Attributes; Behavioral Symptoms; Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; Fatigue; Pathological Conditions, Signs and Symptoms; Behavior; Signs and Symptoms; Post-Acute COVID-19 Syndrome; Mental Fatigue
• Other Study ID Numbers: 23-000654

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No