Mechanistic Effect of Walnut Consumption on Sleep Quality

Poor sleep quality is very common in modern society. Walnuts contain many nutrients that may be helpful for sleep, including melatonin and polyphenols. Some studies show that eating foods high in melatonin and polyphenols improves sleep quality, but walnuts have not been studied specifically. This study proposes to test if eating walnuts improves sleep compared to a food that lacks these sleep-promoting factors. The investigators expect that walnut consumption for 4 days will increase melatonin levels and lead to better sleep quality compared to a high-carbohydrate, high-sugar food. The study will enroll middle-aged and older adults with sleep complaints to participate in this study. Each person will eat the two different foods for 4 days each in random order. The 4-day periods will be separated by at least 2-3 weeks. Sleep quality will be measured by questionnaire and with a wrist monitor every day. The investigators will also do a sleep study using electroencephalography (EEG) on night 3 and take measures of circadian physiology (natural body rhythms) in the laboratory on day 4 (including overnight) by measuring body temperature and blood and urine melatonin. The study findings may provide new options to improve sleep health from increased walnut consumption.

Study Overview

• Status: Recruiting
• Conditions: Poor Sleep Quality
• Intervention / Treatment: Other: Walnut consumption; Other: HCHS consumption

Detailed Description

Walnuts are a nutrient-rich food which provides melatonin and polyphenols. While there is evidence that dietary intakes of foods high in melatonin and polyphenols positively influence sleep quality, the effect of walnuts has not been investigated. The investigators propose to fill this knowledge gap by testing the effects of walnut consumption on serum melatonin and resulting sleep and circadian biology. The study hypotheses are that walnut consumption for 4 days will increase melatonin levels, suggestive of more robust circadian rhythms, and lead to better sleep quality compared to a high-carbohydrate high-sugar (HCHS) equivalent. Using a randomized controlled crossover trial, the study aims to: 1) determine the effect of walnut vs HCHS consumption on melatonin levels; and 2) determine the effect of walnut vs HCHS consumption on sleep and circadian physiology. Adult males and females with poor sleep quality will consume three servings/day of walnuts or an equicaloric HCHS food for 4 days. Sleep quality will be measured nightly using the Karolinska Sleep Diary and wrist actigraphy; sleep architecture from polysomnography will be measured on night 3. Circadian physiology will be assessed on day 4 using body temperature and hourly serum melatonin and on the morning of day 5 from overnight urinary 6-sulfatoxymelatonin. Given the extent of poor sleep, our findings may open new avenues to improve sleep health from increased walnut consumption.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Claudia Dreyer, BS; Phone Number: 347-881-6008; Email: cd3003@cumc.columbia.edu
• Study Contact Backup: Name: Joseariel Romero; Phone Number: 347-963-8845; Email: jr4119@cumc.columbia.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Irving Medical Center
      • Principal Investigator: Marie-Pierre St-Onge, PhD
      • Contact: Claudia Dreyer, BS; Phone Number: 347-881-6008; Email: cd3003@cumc.columbia.edu
      • Contact: Joseariel Romero; Phone Number: 347-963-8845; Email: jr4119@cumc.columbia.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Equal numbers of men and women (12 male and 12 post-menopausal female)
• Equal number of individuals with normal weight (18.5-24.9 kg/m2) and overweight (25-29.9 kg/m2)
• Participants will self-report poor sleep quality, reflected by a global score >5 on Pittsburgh Sleep Quality Index

Exclusion Criteria:

• Diagnosed sleep disorder

• Participants with conditions that could affect sleep will be excluded:

  • smoking, excessive caffeine intake (>300 mg/day)
  • shift work
  • chronic pain
  • diagnosis of a chronic disease (e.g., uncontrolled hypertension, pre-diabetes, type 2 diabetes, chronic kidney disease, chronic obstructive pulmonary disease),
  • autoimmune diseases
  • cardiovascular event or cancer in the past 24 months
  • psychiatric/neurologic disease or disorder, or sleep disorder (diagnosed or high risk for sleep apnea, chronic insomnia, restless leg syndrome, narcolepsy)
  • use of medications that influence CYP1A2 enzymes
• Allergy/intolerance to nuts, tree nuts, or unwilling to eat study foods

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Walnut - washout - HCHS; Participants will consume 3 servings/day of walnuts (3 oz/d) over 4 days and have a washout for 2-3 weeks then crossover to consume 3 equicaloric servings of a HCHS food over 4 days. Over each 4-day period, participants will sleep and eat at home for the first 3 days and will be admitted to the Inpatient Clinical Research Resource of the Irving Institute for Clinical and Translational Research of CUIMC on day 4 for in-depth profiling circadian physiology. Participants will be discharged on the morning of day 5.	Other: Walnut consumption; Participants will add one serving (1 oz) of walnuts at their self-defined breakfast, lunch, and dinner for 4 days. The study will provide study foods at 3 main meals each day to evaluate a temporal effect of the food on melatonin concentrations throughout the day.; Other: HCHS consumption; Participants will add one HCHS food (one PopTarts® pastry) to each of their 3 main meals of the day for 4 days. The study will provide study foods at 3 main meals each day to evaluate a temporal effect of the food on melatonin concentrations throughout the day. An energy-matched high-carbohydrate, high-sugar (HCHS) alternative, representative of a common US snack food, on sleep quality in adults with habitually poor sleep quality.
Experimental: HCHS - washout - Walnut; Participants will consume 3 equicaloric servings of a HCHS food over 4 days and have a washout for 2-3 weeks then crossover to consume 3 servings/day of walnuts (3 oz/d) for 4 days. Over each 4-day period, participants will sleep and eat at home for the first 3 days and will be admitted to the Inpatient Clinical Research Resource of the Irving Institute for Clinical and Translational Research of CUIMC on day 4 for in-depth profiling circadian physiology. Participants will be discharged on the morning of day 5.	Other: Walnut consumption; Participants will add one serving (1 oz) of walnuts at their self-defined breakfast, lunch, and dinner for 4 days. The study will provide study foods at 3 main meals each day to evaluate a temporal effect of the food on melatonin concentrations throughout the day.; Other: HCHS consumption; Participants will add one HCHS food (one PopTarts® pastry) to each of their 3 main meals of the day for 4 days. The study will provide study foods at 3 main meals each day to evaluate a temporal effect of the food on melatonin concentrations throughout the day. An energy-matched high-carbohydrate, high-sugar (HCHS) alternative, representative of a common US snack food, on sleep quality in adults with habitually poor sleep quality.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum melatonin	Serum melatonin will be measured via last testing of blood samples collected on day 4, in an inpatient setting. Repeated for each phase.	Baseline (9AM; Hour 0), Hour 1, Hour 2, Hour 3, Hour 4, Hour 5, Hour 6, Hour 7, Hour 8, Hour 9, Hour 10, Hour 11, Hour 12, Hour 13, Hour 14, Hour 15 (Midnight)
Sleep quality index	Sleep quality will be assessed daily using wrist actigraphy. Variables include sleep fragmentation index and sleep efficiency. Repeated for each phase.	Night 1, Night 2, Night 3, Night 4
Slow wave sleep index	Slow wave sleep will be measured using electroencephalography, in the participant's home. Repeated for each phase.	Night 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6-sulfatoxymelatonin level	This is to measure Melatonin production in urine samples. Repeated for each phase.	Night 4 to morning of Day 5 (Approximately up to 12 hours)
Body temperature	Proximal to distal body temperature gradient measured using thermochron devices (iButtons). Repeated for each phase. In patient. Over 24 hours.	Day 4
Sleep quality score	Self-reported sleep quality assessed using the Karolinska Sleep Diary (higher score represents better sleep). Repeated for each phase.	Days 2, 3, 4, 5

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
NFkB level	This is to measure Endothelial cell inflammation in endothelial cells collected from a forearm vein. Repeated for each phase. Fasted sample.	Day 4 (or Day 5)

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: United States Department of Agriculture (USDA); California Walnut Commission
• Investigators: Principal Investigator: Marie-Pierre St-Onge, PhD, Associate Professor of Nutritional Medicine

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: May 21, 2024
• First Submitted That Met QC Criteria: May 21, 2024
• First Posted (Actual): May 28, 2024

Study Record Updates

• Last Update Posted (Actual): July 31, 2025
• Last Update Submitted That Met QC Criteria: July 29, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Dietary intervention; Controlled feeding; Randomized crossover study; Inpatient visit; Outpatient monitoring
• Other Study ID Numbers: AAAV1362; GRANT13949102 (Other Grant/Funding Number: USDA/NIFA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be submitted to Zenodo, a generalist repository that is participating in the NIH Generalist Repository Ecosystem Initiative. We will submit metadata associated with the datasets to Zenodo. The repository will provide metadata, persistent identifiers, and long-term access for open and controlled access. Each study created in Zenodo is assigned a digital object identifier (DOI). This data DOI will be referenced in the publication to allow the research community easy access to the exact data used in the publication. To request access of the data, researchers will use the standard processes at Zenodo. Given that we seek the widest possible availability, in most cases all that is necessary is obtaining a Zenodo account from the repository web site.
• IPD Sharing Time Frame: Within 12 months of final study completion.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

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