Influence of Walnut Intake on Vascular Function and Metabolism

Overweight and Obesity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03900403
• Other study ID #: 1313232
• Status: Completed
• Phase: N/A
• Start date: September 1, 2019
• Est. completion date: June 14, 2023

Study information

• Verified date: August 2023
• Source: University of California, Davis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: June 14, 2023
• Est. primary completion date: June 14, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 45 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cardiovascular Risk Factor
• Endothelial Dysfunction
• Overweight
• Overweight and Obesity

Intervention

Other:
• Walnut Intake
40g of daily walnut intake for 12 weeks

Locations

Country	Name	City	State
United States	Department of Nutrition	Davis	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, Davis

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Blood Pressure	Office blood pressure	18 weeks
Other	Complete Metabolic Panel	Will include liver enzymes and glucose	18 weeks
Other	Complete Blood Cell Count	w Will include total platelet number and mean platelet volume	18 weeks
Other	Lipid Panel	Will assess fasting cholesterol and triglyceride levels	18 weeks
Other	Skin Health	Will assess fine facial wrinkles and redness	18 weeks
Primary	Reactive Hyperemia Index (RHI)	Digital microvascular function as measured by the EndoPAT2000	18 weeks
Primary	Framingham Reactive Hyperemia Index (fRHI)	Digital microvascular function as measured by the EndoPAT2000	18 weeks
Secondary	Collagen-Induced Platelet Aggregation	Optical platelet aggregometry	18 weeks
Secondary	ADP-Induced Platelet Aggregation	Optical platelet aggregometry	18 weeks
Secondary	Plasma Fatty Acids	Circulating levels of non-esterified fatty acids	18 weeks
Secondary	Plasma Oxylipins	Circulating levels of non-esterified oxylipins	18 weeks
Secondary	Esterified Oxylipins	Lipoprotein esterified oxylipins	18 weeks
Secondary	Esterified Fatty Acids	Lipoprotein esterified fatty acids	18 weeks
Secondary	Urolithin Metabolites	Conjugated and unconjugated urolithins	18 weeks
Secondary	Ellagitannin Metabolites	Conjugated and unconjugated Ellagitanin-derived metabolites	18 weeks
Secondary	Total Nitrate and Nitrite	Total nitrate derived from the diet	18 weeks
Secondary	Nitric Oxide metabolites (RNOX)	Nitric oxide metabolites produced from the intervention	18 weeks

External Links

•   Learn more or sign up for the study here!