search
Back to results

Influence of Walnut Intake on Vascular Function and Metabolism

Primary Purpose

Overweight and Obesity, Endothelial Dysfunction, Cardiovascular Risk Factor

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Walnut Intake
Sponsored by
University of California, Davis
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Overweight and Obesity

Eligibility Criteria

45 Years - 65 Years (Adult, Older Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

  • Postmenopausal female: 45-65 years
  • Women: lack of menses for at least two years.
  • Subject is willing and able to comply with the study protocols.
  • Subject is willing to participate in all study procedures
  • BMI 25.0 - 35 kg/m2

Exclusion Criteria:

  • BMI ≥ 35 kg/m2
  • Visit 1 Reactive Hyperemia Index (RHI; EndoPAT 2000) ≥ 2.4
  • Dislike or allergy for walnuts or walnut products
  • Self-reported use of daily anticoagulation agents including aspirin, NSAIDs
  • Vegan, Vegetarians, food faddists or those consuming a non-traditional diet
  • Fruit consumption ≥ 3 cups/day
  • Regular consumption of nuts (2-3 servings/week)
  • Vegetable consumption ≥ 4 cups/day for females
  • Coffee/tea ≥ 3 cups/day
  • Dark chocolate ≥ 3 oz/day
  • Self-reported restriction of physical activity due to a chronic health condition
  • Self-reported chronic/routine high intensity exercise
  • Self-reported diabetes
  • Blood pressure ≥ 140/90 mm Hg
  • Self-reported renal or liver disease
  • Self-reported heart disease, which includes cardiovascular events and stroke
  • Peripheral artery disease, Raynaud's syndrome or disease
  • Inability to properly place or wear the PAT probes or abnormal measurements on pre-screening PAT
  • Abnormal Metabolic or CBC panels (laboratory values outside the reference range) if determined to be clinically significant by the study physician.
  • Self-reported cancer within past 5 years
  • Self-reported malabsorption
  • Currently taking prescription drugs or supplements.
  • Supplement use other than a general formula of vitamins and minerals that meet the RDA
  • Not willing to stop any supplement use, including herbal, plant or botanical, fish oil, oil supplements a month prior to study enrollment.
  • Indications of substance or alcohol abuse within the last 3 years
  • Cannabis use
  • Screening LDL ≥ 190 mg/dl for those who have 0-1 major risk factors apart from LDL cholesterol (i.e. family history of premature coronary artery disease (male first degree relative < 55 years; CHD in female first degree relative < 65 years), cigarette smoker, HDL-C ≤ 40 mg/dL]. (using NCEP calculator http://cvdrisk.nhlbi.nih.gov/calculator.asp)
  • Screening LDL ≥ 160 mg/dl for those who have 2 major risk factors apart from LDL cholesterol [i.e. family history of premature coronary artery disease (male first degree relative < 55 years; CHD in female first degree relative < 65 years), cigarette smoker, HDL-C ≤ 40 mg/dL]. (using NCEP calculator http://cvdrisk.nhlbi.nih.gov/calculator.asp);
  • Screening LDL ≥ 130 mg/dl for those who have 2 major risk factors apart from LDL cholesterol [i.e. family history of premature coronary artery disease (male first degree relative < 55 years; CHD in female first degree relative < 65 years), cigarette smoker, HDL-C ≤ 40 mg/dL], and a Framingham 10-year Risk Score 10-20% (using NCEP calculator http://cvdrisk.nhlbi.nih.gov/calculator.asp).
  • Current enrollee in a clinical research study.

Sites / Locations

  • Department of Nutrition

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

Habitual Intake

Walnut Intake

Arm Description

This will be the comparative arm, of 6 weeks before and after the study participant is on their habitual diet

Experimental Arm of 12 weeks of Walnut Intake, with study visits at baseline (prior to walnut intake) and after 6 and 12 weeks of 40g of Walnut Intake.

Outcomes

Primary Outcome Measures

Reactive Hyperemia Index (RHI)
Digital microvascular function as measured by the EndoPAT2000
Framingham Reactive Hyperemia Index (fRHI)
Digital microvascular function as measured by the EndoPAT2000

Secondary Outcome Measures

Collagen-Induced Platelet Aggregation
Optical platelet aggregometry
ADP-Induced Platelet Aggregation
Optical platelet aggregometry
Plasma Fatty Acids
Circulating levels of non-esterified fatty acids
Plasma Oxylipins
Circulating levels of non-esterified oxylipins
Esterified Oxylipins
Lipoprotein esterified oxylipins
Esterified Fatty Acids
Lipoprotein esterified fatty acids
Urolithin Metabolites
Conjugated and unconjugated urolithins
Ellagitannin Metabolites
Conjugated and unconjugated Ellagitanin-derived metabolites
Total Nitrate and Nitrite
Total nitrate derived from the diet
Nitric Oxide metabolites (RNOX)
Nitric oxide metabolites produced from the intervention

Full Information

First Posted
March 31, 2019
Last Updated
August 30, 2023
Sponsor
University of California, Davis
search

1. Study Identification

Unique Protocol Identification Number
NCT03900403
Brief Title
Influence of Walnut Intake on Vascular Function and Metabolism
Official Title
The Influence of Daily Walnut Intake on Vascular Function and Associated Changes in Lipid Mediators and Primary Metabolites.
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
September 1, 2019 (Actual)
Primary Completion Date
June 14, 2023 (Actual)
Study Completion Date
June 14, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, Davis

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This study seeks to confirm and extend previous finding that four weeks of daily intake of 40 g of walnuts improve microvascular function, increasing the reactive hyperemia index (RHI), effects which were greatest in individuals with the worst initial RHI and correlating to circulating levels of vasoactive plasma epoxides. The current trial will enroll postmenopausal women who are at risk for cardiovascular disease due to their menopausal status and increased central adiposity. The initial trial focused on non-esterified (i.e. plasma) derived oxylipins, but substantial and unique changes were also observed in the esterified lipoprotein pool. The current study will add the esterified lipoprotein pool, important, as the mechanisms by which walnut intake influences endothelial function are currently undefined, but may include lipoprotein induced modulation of vascular hemostasis. As a secondary objective, primary metabolism and urolithin metabotype will be analyzed as a way to capture the influence of potential differences in habitual diet and metabolism on physiologic response. Therefore, this study will combine measures of cardiovascular physiology, metabolomics, and walnut-derived metabolite analyses to assess the 12 week influence of 40 g of daily walnut intake on the health of overweight and obese postmenopausal women.
Detailed Description
A dietary intervention trial will be conducted to achieve the following objectives and outcomes: Objective 1: Determine the 12 week change in bioactive lipid mediators, and their relationship to vascular function and platelet reactivity in overweight or obese postmenopausal women with walnut incorporation into their habitual diet. Objective 2: Assess the contribution of metabolic phenotype on the variance in biomarker response that includes both primary metabolism and urolithin metabotype. Expected Outcomes: Forty g of daily walnut intake for six- and 12- weeks is predicted to positively impact the production of bioactive lipid mediators known to favorably regulate cardiovascular and inflammatory signaling. AA derived oxylipins produced from COX, LOX, and CYP epoxygenases are known as regulators of inflammation, platelet activation and vascular function. Therefore, understanding how certain foods such as walnuts can change the relative ratio of PUFA substrates (i.e., AA, ALA, LA, EPA and DHA), and their subsequent bioactive species produced through these enzyme pathways is necessary for the refinement of dietary recommendations with regard to specific foods and dietary patterns aimed at reducing the risk of chronic disease. Although a positive outcome is predicted, there may be substantial variability in response. To explore potential genetic and dietary factors that may contribute to the variability in response to the above functional markers, primary metabolism and urolithin metabotype will be assessed. Objective 3: Assess the influence of 12 weeks of walnut intake on facial wrinkles in postmenopausal women. Expected Outcome: Tweleve weeks of 40 g of walnut intake will improve facial wrinkles and erythema in the study population, and the improvements will be related to changes in metabotype.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Overweight and Obesity, Endothelial Dysfunction, Cardiovascular Risk Factor

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
Open-arm study, comparing the effects of 12 weeks of 40g of walnut intake to 6 weeks of the study participant's habitual diet.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Habitual Intake
Arm Type
No Intervention
Arm Description
This will be the comparative arm, of 6 weeks before and after the study participant is on their habitual diet
Arm Title
Walnut Intake
Arm Type
Experimental
Arm Description
Experimental Arm of 12 weeks of Walnut Intake, with study visits at baseline (prior to walnut intake) and after 6 and 12 weeks of 40g of Walnut Intake.
Intervention Type
Other
Intervention Name(s)
Walnut Intake
Intervention Description
40g of daily walnut intake for 12 weeks
Primary Outcome Measure Information:
Title
Reactive Hyperemia Index (RHI)
Description
Digital microvascular function as measured by the EndoPAT2000
Time Frame
18 weeks
Title
Framingham Reactive Hyperemia Index (fRHI)
Description
Digital microvascular function as measured by the EndoPAT2000
Time Frame
18 weeks
Secondary Outcome Measure Information:
Title
Collagen-Induced Platelet Aggregation
Description
Optical platelet aggregometry
Time Frame
18 weeks
Title
ADP-Induced Platelet Aggregation
Description
Optical platelet aggregometry
Time Frame
18 weeks
Title
Plasma Fatty Acids
Description
Circulating levels of non-esterified fatty acids
Time Frame
18 weeks
Title
Plasma Oxylipins
Description
Circulating levels of non-esterified oxylipins
Time Frame
18 weeks
Title
Esterified Oxylipins
Description
Lipoprotein esterified oxylipins
Time Frame
18 weeks
Title
Esterified Fatty Acids
Description
Lipoprotein esterified fatty acids
Time Frame
18 weeks
Title
Urolithin Metabolites
Description
Conjugated and unconjugated urolithins
Time Frame
18 weeks
Title
Ellagitannin Metabolites
Description
Conjugated and unconjugated Ellagitanin-derived metabolites
Time Frame
18 weeks
Title
Total Nitrate and Nitrite
Description
Total nitrate derived from the diet
Time Frame
18 weeks
Title
Nitric Oxide metabolites (RNOX)
Description
Nitric oxide metabolites produced from the intervention
Time Frame
18 weeks
Other Pre-specified Outcome Measures:
Title
Blood Pressure
Description
Office blood pressure
Time Frame
18 weeks
Title
Complete Metabolic Panel
Description
Will include liver enzymes and glucose
Time Frame
18 weeks
Title
Complete Blood Cell Count
Description
w Will include total platelet number and mean platelet volume
Time Frame
18 weeks
Title
Lipid Panel
Description
Will assess fasting cholesterol and triglyceride levels
Time Frame
18 weeks
Title
Skin Health
Description
Will assess fine facial wrinkles and redness
Time Frame
18 weeks

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Postmenopausal female: 45-65 years Women: lack of menses for at least two years. Subject is willing and able to comply with the study protocols. Subject is willing to participate in all study procedures BMI 25.0 - 35 kg/m2 Exclusion Criteria: BMI ≥ 35 kg/m2 Visit 1 Reactive Hyperemia Index (RHI; EndoPAT 2000) ≥ 2.4 Dislike or allergy for walnuts or walnut products Self-reported use of daily anticoagulation agents including aspirin, NSAIDs Vegan, Vegetarians, food faddists or those consuming a non-traditional diet Fruit consumption ≥ 3 cups/day Regular consumption of nuts (2-3 servings/week) Vegetable consumption ≥ 4 cups/day for females Coffee/tea ≥ 3 cups/day Dark chocolate ≥ 3 oz/day Self-reported restriction of physical activity due to a chronic health condition Self-reported chronic/routine high intensity exercise Self-reported diabetes Blood pressure ≥ 140/90 mm Hg Self-reported renal or liver disease Self-reported heart disease, which includes cardiovascular events and stroke Peripheral artery disease, Raynaud's syndrome or disease Inability to properly place or wear the PAT probes or abnormal measurements on pre-screening PAT Abnormal Metabolic or CBC panels (laboratory values outside the reference range) if determined to be clinically significant by the study physician. Self-reported cancer within past 5 years Self-reported malabsorption Currently taking prescription drugs or supplements. Supplement use other than a general formula of vitamins and minerals that meet the RDA Not willing to stop any supplement use, including herbal, plant or botanical, fish oil, oil supplements a month prior to study enrollment. Indications of substance or alcohol abuse within the last 3 years Cannabis use Screening LDL ≥ 190 mg/dl for those who have 0-1 major risk factors apart from LDL cholesterol (i.e. family history of premature coronary artery disease (male first degree relative < 55 years; CHD in female first degree relative < 65 years), cigarette smoker, HDL-C ≤ 40 mg/dL]. (using NCEP calculator http://cvdrisk.nhlbi.nih.gov/calculator.asp) Screening LDL ≥ 160 mg/dl for those who have 2 major risk factors apart from LDL cholesterol [i.e. family history of premature coronary artery disease (male first degree relative < 55 years; CHD in female first degree relative < 65 years), cigarette smoker, HDL-C ≤ 40 mg/dL]. (using NCEP calculator http://cvdrisk.nhlbi.nih.gov/calculator.asp); Screening LDL ≥ 130 mg/dl for those who have 2 major risk factors apart from LDL cholesterol [i.e. family history of premature coronary artery disease (male first degree relative < 55 years; CHD in female first degree relative < 65 years), cigarette smoker, HDL-C ≤ 40 mg/dL], and a Framingham 10-year Risk Score 10-20% (using NCEP calculator http://cvdrisk.nhlbi.nih.gov/calculator.asp). Current enrollee in a clinical research study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Roberta R Holt, PhD
Organizational Affiliation
University of California, Davis
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Nutrition
City
Davis
State/Province
California
ZIP/Postal Code
95616
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
https://studypages.com/s/walnut-study-411535/
Description
Learn more or sign up for the study here!

Learn more about this trial

Influence of Walnut Intake on Vascular Function and Metabolism

We'll reach out to this number within 24 hrs