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Completed

NCT Number: NCT03900403

Influence of Walnut Intake on Vascular Function and Metabolism

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.

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Key information

Age range

45 year–65 year

Sex eligibility

Female

Study type

Interventional

Phase

Not applicable

Primary location

Department of Nutrition

Davis, California, 95616, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Walnut intake

Other

40g of daily walnut intake for 12 weeks

Primary outcomes

  1. Reactive Hyperemia Index (RHI)

    Time frame: 18 weeks

    Digital microvascular function as measured by the EndoPAT2000

  2. Framingham Reactive Hyperemia Index (fRHI)

    Time frame: 18 weeks

    Digital microvascular function as measured by the EndoPAT2000

Secondary outcomes

  1. Collagen-Induced Platelet Aggregation

    Time frame: 18 weeks

    Optical platelet aggregometry

  2. ADP-Induced Platelet Aggregation

    Time frame: 18 weeks

    Optical platelet aggregometry

  3. Plasma Fatty Acids

    Time frame: 18 weeks

    Circulating levels of non-esterified fatty acids

  4. Plasma Oxylipins

    Time frame: 18 weeks

    Circulating levels of non-esterified oxylipins

  5. Esterified Oxylipins

    Time frame: 18 weeks

    Lipoprotein esterified oxylipins

  6. Esterified Fatty Acids

    Time frame: 18 weeks

    Lipoprotein esterified fatty acids

  7. Urolithin Metabolites

    Time frame: 18 weeks

    Conjugated and unconjugated urolithins

  8. Ellagitannin Metabolites

    Time frame: 18 weeks

    Conjugated and unconjugated Ellagitanin-derived metabolites

  9. Total Nitrate and Nitrite

    Time frame: 18 weeks

    Total nitrate derived from the diet

  10. Nitric Oxide metabolites (RNOX)

    Time frame: 18 weeks

    Nitric oxide metabolites produced from the intervention

Other outcomes

  1. Blood Pressure

    Time frame: 18 weeks

    Office blood pressure

  2. Complete Metabolic Panel

    Time frame: 18 weeks

    Will include liver enzymes and glucose

  3. Complete Blood Cell Count

    Time frame: 18 weeks

    w Will include total platelet number and mean platelet volume

  4. Lipid Panel

    Time frame: 18 weeks

    Will assess fasting cholesterol and triglyceride levels

  5. Skin Health

    Time frame: 18 weeks

    Will assess fine facial wrinkles and redness

Sponsors and collaborators

Lead sponsor

University of California, Davis

Other

Registry information

Official study title

The Influence of Daily Walnut Intake on Vascular Function and Associated Changes in Lipid Mediators and Primary Metabolites.

Important dates

Study start
2019
Primary completion
2023
Study completion
2023
First posted
Apr 3, 2019
Registry last updated
Aug 31, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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