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CompletedNCT03900403Updated Aug 31, 2023

Influence of Walnut Intake on Vascular Function and Metabolism

An interventional study of Walnut Intake in Overweight and Obesity, Endothelial Dysfunction and Cardiovascular Risk Factor, sponsored by University of California, Davis. Completed at 1 site in United States. Open to female participants aged 45 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2023-08-31.

Sponsored by University of California, Davis · Not applicable, Interventional, and Basic science

Phase
Not applicable
Study type
Interventional
Enrollment
20
Allocation
Non-randomized
Ages
45 Years to 65 Years
Sex
Female
01

Study 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.

Read the 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.

02

Conditions studied

  • Overweight and Obesity
  • Endothelial Dysfunction
  • Cardiovascular Risk Factor

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03

In context

Overweight

3,670 studies on the registry are indexed under Overweight; 849 are open to participants now.

This study's enrollment of 20 is below the median of 73 across 3,175 interventional studies indexed under Overweight.

Browse Overweight studies →

Lead sponsor

University of California, Davis is the lead sponsor of 798 studies on the registry; 146 are open to participants now.

Of its 65 completed or terminated interventional studies of FDA-regulated products, 43 (66%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
45 Years to 65 Years
Sexes eligible
Female
Accepts healthy volunteers
Yes

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

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.
05

Study design

Phase
Not applicable
Primary purpose
Basic science
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
20 participants (actual)

Study arms

  • No intervention
    Habitual Intake

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

  • Experimental
    Walnut Intake

    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.

    Other: Walnut Intake

Interventions

  • OtherWalnut Intake

    40g of daily walnut intake for 12 weeks

06

What researchers measure

Primary outcomes

  1. Reactive Hyperemia Index (RHI)

    Digital microvascular function as measured by the EndoPAT2000

    Time frame: 18 weeks

  2. Framingham Reactive Hyperemia Index (fRHI)

    Digital microvascular function as measured by the EndoPAT2000

    Time frame: 18 weeks

Secondary outcomes

  1. Collagen-Induced Platelet Aggregation

    Optical platelet aggregometry

    Time frame: 18 weeks

  2. ADP-Induced Platelet Aggregation

    Optical platelet aggregometry

    Time frame: 18 weeks

  3. Plasma Fatty Acids

    Circulating levels of non-esterified fatty acids

    Time frame: 18 weeks

  4. Plasma Oxylipins

    Circulating levels of non-esterified oxylipins

    Time frame: 18 weeks

  5. Esterified Oxylipins

    Lipoprotein esterified oxylipins

    Time frame: 18 weeks

  6. Esterified Fatty Acids

    Lipoprotein esterified fatty acids

    Time frame: 18 weeks

  7. Urolithin Metabolites

    Conjugated and unconjugated urolithins

    Time frame: 18 weeks

  8. Ellagitannin Metabolites

    Conjugated and unconjugated Ellagitanin-derived metabolites

    Time frame: 18 weeks

  9. Total Nitrate and Nitrite

    Total nitrate derived from the diet

    Time frame: 18 weeks

  10. Nitric Oxide metabolites (RNOX)

    Nitric oxide metabolites produced from the intervention

    Time frame: 18 weeks

Other outcomes

  1. Blood Pressure

    Office blood pressure

    Time frame: 18 weeks

  2. Complete Metabolic Panel

    Will include liver enzymes and glucose

    Time frame: 18 weeks

  3. Complete Blood Cell Count

    w Will include total platelet number and mean platelet volume

    Time frame: 18 weeks

  4. Lipid Panel

    Will assess fasting cholesterol and triglyceride levels

    Time frame: 18 weeks

  5. Skin Health

    Will assess fine facial wrinkles and redness

    Time frame: 18 weeks

07

Study locations

1 site
  • Department of Nutrition
    Davis, California 95616, United States
08

References and documents

Individual participant data

Plan to share: No

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 31, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT03900403
Lead sponsor
University of California, Davis
Responsible party
Sponsor
First posted
Apr 3, 2019
Start date
Sep 1, 2019
Primary completion
Jun 14, 2023
Completion
Jun 14, 2023
Last update
Aug 31, 2023

Study contacts

Roberta R Holt, PhD
principal investigator · University of California, Davis

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Aug 2023. You cannot join it, but the record below documents what was studied.

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