Effect of Walnuts on Cognitive Function and Gut Microbiome in Older Adults

The purpose of this study is to examine the impact of daily consumption of walnuts for 12 weeks on cognitive function, markers of inflammation and oxidative stress, and the gut microbiome in healthy adults age 55 years and older.

Study Overview

• Status: Recruiting
• Conditions: Aging; Inflammation Biomarkers
• Intervention / Treatment: Other: Walnuts; Other: Crackers

Detailed Description

The investigators will determine the extent to which daily consumption of walnuts by older adults for 12 weeks influences cognitive function and whether improvements are associated with changes in the resident gut microbiota. The investigators propose that age-related cognitive decline can be mitigated by consuming walnuts, by modulating the microbiota and microbial metabolites and decreasing oxidative stress and inflammation.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Emily Ho, PhD; Phone Number: 541-737-9559; Email: emily.ho@oregonstate.edu
• Study Contact Backup: Name: Sandra Uesugi, RN, BSN, MS; Phone Number: 541-737-3594; Email: sandra.uesugi@oregonstate.edu

Study Locations

• United States
  • Oregon
    • Corvallis, Oregon, United States, 97331
      • Recruiting
      • Oregon State University
      • Contact: Sandra Uesugi, RN, BSN, MS; Phone Number: 541-737-3594; Email: sandra.uesugi@oregonstate.edu
      • Principal Investigator: Emily Ho, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age 55 years or older
• Able to hear well enough to understand spoken instructions and questions
• Able to see well enough to read and respond to printed instructions and fill out questionnaires (corrective lenses are allowed)
• Able to write legibly and move a computer joystick with at least one hand (i.e., no injury or connective tissue or joint disorder that would impair ability to write or make hand movements)
• Able to speak, read, and understand English
• Score of greater than 79 on water maze learning task
• Willing to maintain current eating patterns
• Willing and able to complete the cognitive tests
• Willing to stop consuming almonds, Brazil nuts, cashews, chestnuts, hazelnuts, macadamia nuts, peanuts, pecans, pistachios, walnuts, persimmons and pomegranates for 14 weeks. - are nuts or contain ellagitannins or ellagic acid - compounds/foods of interest for this study
• Willing to limit oak aged wines and spirits to 1 serving/day and limit blackberries (including similar berries like boysenberries, marionberries, and olallieberries), cloudberries, cranberries, currants, elderberries, lingonberries, raspberries, strawberries, wolfberries, other native berries; guava, mango, muscadine grapes, nectarines, peaches, plums, pluots to 1 cup/day for 14 weeks; REMAIN CONSISTENT (consistent intake levels of): Coffee, tea, apple, apricots, blueberries, cherries, grapes (table/common)
• Willing to stop probiotic supplements 2 weeks prior to and during the study (14 weeks)

Exclusion Criteria:

• Consumption of walnuts, pecans, and chestnuts combined greater than 2 oz / week in the past 3 months.
• Use of oral antibiotics in the past month
• Regular use of oral anti-inflammatory medications in the past month
• Nut, wheat, or gluten allergy/intolerance
• Pregnant or planning to become pregnant during the study period
• Weighs less than 110 pounds
• Diagnosis of sickle cell disease
• Susceptibility to motion sickness
• Consumes 3 or more alcoholic drinks daily
• History of smoking tobacco products, including e-cigarettes and vaporizers in the past 2 years (smokeless tobacco use not exclusionary)
• Use of psilocybin or cannabis products (including CBD-only products) in the past 2 years
• Current treatment for alcohol or other substance use disorder
• History of heart attack, heart failure, or stroke, including transient ischemic attack
• History of liver disease or kidney disease requiring dialysis
• History of cancer in the past 5 years (Skin cancer that was only surgically treated is not exclusionary)
• History of bariatric surgery (e.g., gastric bypass, gastric banding, sleeve gastrectomy, etc.) or disorders (e.g., Crohn's disease, unmanaged celiac disease, ulcerative colitis)
• History of thyroid disorder that requires medication, but subject is not taking medication
• History of chronic bronchitis or emphysema
• Diagnosis of dementia or Alzheimer's disease
• History of head injury requiring hospitalization or loss of consciousness > 5 minutes
• History of chronic migraines (for at least 3 months, headache occurring on 15 or more days per month, where at least 8 of those headache days have migraine symptoms)
• Blood pressure above 159 (systolic) or 99 (diastolic) mm Hg
• Corrected vision worse than 20/50
• Score of less than 10/15 on Ishihara color vision test or diagnosis of color blindness
• Score of less than 26/30 on Mini-Mental State Exam
• Score of greater than 15 on Center for Epidemiologic Depression survey
• History of disease or disorder which causes cognitive impairment, including but limited to: attention-deficit/hyperactivity disorder (ADHD), amyotrophic lateral sclerosis, autism, bipolar disorder, Down's syndrome, encephalitis, epilepsy/seizures, human immunodeficiency virus (HIV), Huntington's disease, Korsakoff's psychosis, multiple sclerosis, Parkinson's disease, or psychotic disorders (e.g., schizophrenia, schizoaffective disorder, schizophreniform disorder)
• Current and regular use of any of the following medications: insulin, opioids, anti-seizure medications, psychotropic medications: stimulants, anti-psychotics, or medications that cause daytime drowsiness or difficulty concentrating

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Walnuts; Daily consumption of 1.5 ounces (42.5 g) of plain walnuts for 12 weeks	Other: Walnuts; Daily consumption of 1.5 ounces of plain walnuts for 12 weeks
Placebo Comparator: Crackers; Daily consumption of non-whole grain crackers for 12 weeks (caloric equivalent to 1.5 ounces of plain walnuts)	Other: Crackers; Daily consumption of non-whole grain crackers for 12 weeks (caloric equivalent to 1.5 ounces of plain walnuts)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive function - memory	Change from baseline at week 12: age adjusted standard scores (higher score reflects positive outcome)	0 and 12 weeks
Cognitive function - memory	Change from baseline at week 12: proximity (lower score reflects positive outcome)	0 and 12 weeks
Cognitive function - cognitive flexibility	Change from baseline at week 12: age adjusted standard scores (higher score reflects positive outcome)	0 and 12 weeks
Cognitive function - cognitive flexibility	Change from baseline at week 12: proximity (lower score reflects positive outcome)	0 and 12 weeks
Cognitive function - speed of processing	Change from baseline at week 12: age adjusted standard scores (higher score reflects positive outcome)	0 and 12 weeks
Gut microbiome composition	Change from baseline at week 12: microbiome composition	0 and 12 weeks
Lipid oxidation levels	Change from baseline at week 12: plasma malondialdehyde (MDA)	0 and 12 weeks
Gut permeability and health: Inflammatory biomarkers	Change from baseline at week 12: Gut inflammatory biomarkers fecal calprotectin and myeloperoxidase	0 and 12 weeks
Biomarkers of inflammation	Change from baseline at week 12: Plasma inflammatory markers (ex. CRP and IL-6)	0 and 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urolithin concentrations	Change from baseline at week 12: urolithin A and urolithin B concentrations in urine	0 and 12 weeks
Blood pressure	Change from baseline at week 12: systolic and diastolic blood pressure	0 and 12 weeks
Weight	Change from baseline at week 12: weight	0 and 12 weeks

Collaborators and Investigators

• Sponsor: Oregon State University
• Collaborators: California Walnut Commission
• Investigators: Principal Investigator: Emily Ho, PhD, Oregon State University

Publications and helpful links

Helpful Links

• This website provides detailed study information for potential participants as well as an online screening survey to assess potential eligibility. Additionally, 2 in-person screening visits follow the online screening survey to assess eligibility.

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): May 1, 2029

Study Registration Dates

• First Submitted: April 8, 2025
• First Submitted That Met QC Criteria: April 16, 2025
• First Posted (Actual): April 24, 2025

Study Record Updates

• Last Update Posted (Actual): June 19, 2025
• Last Update Submitted That Met QC Criteria: June 17, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: cognitive function; gut microbiome; walnuts
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation
• Other Study ID Numbers: LPI-1153

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared with other researchers without IRB approval.

Drug and device information, study documents

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