Influence of Walnut Intake on Vascular Function and Metabolism
Condition: Overweight and Obesity; Endothelial Dysfunction; Cardiovascular Risk Factor
MeSH terms: Overweight
Study type: Interventional

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.
    

Intervention name(s): Walnut Intake
Intervention type(s): Other
Intervention description(s): 40g of daily walnut intake for 12 weeks
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Intervention 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)
Primary purpose: Basic Science