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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Habitual Intake | No Intervention | This will be the comparative arm, of 6 weeks before and after the study participant is on their habitual diet | |
| Walnut Intake | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Walnut Intake | Other | 40g of daily walnut intake for 12 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Reactive Hyperemia Index (RHI) | Digital microvascular function as measured by the EndoPAT2000 | 18 weeks |
| Framingham Reactive Hyperemia Index (fRHI) | Digital microvascular function as measured by the EndoPAT2000 | 18 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Collagen-Induced Platelet Aggregation | Optical platelet aggregometry | 18 weeks |
| ADP-Induced Platelet Aggregation | Optical platelet aggregometry |
| Measure | Description | Time Frame |
|---|---|---|
| Blood Pressure | Office blood pressure | 18 weeks |
| Complete Metabolic Panel | Will include liver enzymes and glucose | 18 weeks |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Roberta R Holt, PhD | University of California, Davis | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Nutrition | Davis | California | 95616 | United States |
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| Label | URL |
|---|---|
| Learn more or sign up for the study here! | View source |
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| ID | Term |
|---|---|
| D050177 | Overweight |
| D009765 | Obesity |
| ID | Term |
|---|---|
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
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Open-arm study, comparing the effects of 12 weeks of 40g of walnut intake to 6 weeks of the study participant's habitual diet.
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| 18 weeks |
| Plasma Fatty Acids | Circulating levels of non-esterified fatty acids | 18 weeks |
| Plasma Oxylipins | Circulating levels of non-esterified oxylipins | 18 weeks |
| Esterified Oxylipins | Lipoprotein esterified oxylipins | 18 weeks |
| Esterified Fatty Acids | Lipoprotein esterified fatty acids | 18 weeks |
| Urolithin Metabolites | Conjugated and unconjugated urolithins | 18 weeks |
| Ellagitannin Metabolites | Conjugated and unconjugated Ellagitanin-derived metabolites | 18 weeks |
| Total Nitrate and Nitrite | Total nitrate derived from the diet | 18 weeks |
| Nitric Oxide metabolites (RNOX) | Nitric oxide metabolites produced from the intervention | 18 weeks |
| Complete Blood Cell Count | w Will include total platelet number and mean platelet volume | 18 weeks |
| Lipid Panel | Will assess fasting cholesterol and triglyceride levels | 18 weeks |
| Skin Health | Will assess fine facial wrinkles and redness | 18 weeks |
| D012816 |
| Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |