Muscadine Grape Seed Supplementation and Vascular Function
Condition: Dietary Supplements
Study type: Interventional

Summary: 
      The investigators sought to evaluate the effect of muscadine grape seed supplementation on
      brachial diameter and flow-mediated vasodilator responses in subjects with, or at risk for
      cardiovascular disease.

      Methods: In a randomized, double-blind, placebo-controlled crossover trial, 50 adults (25
      men, 25 women) with one or more cardiac risk factors were randomized to muscadine grape seed
      (MGS) supplement 1300mg daily vs.. placebo for 4 weeks each, with a 4-week washout between
      study periods. Resting diameter and endothelial function measured using brachial
      flow-mediated dilation (FMD) were determined at the beginning and end of each study period.
    

Detailed description: 
      Study Participants Participants were adult male and non-pregnant female outpatients ages
      18-65 with one or more of the following cardiovascular risk factors: hypertension (blood
      pressure ≥ 140/90 or current treatment for hypertension); dyslipidemia (total cholesterol >
      220 mg/dL + LDL cholesterol > 130 mg/dL, or current use of lipid-lowering medications); or
      controlled type 2 diabetes mellitus (glycated hemoglobin < 8.0 % with or without medication).
      Subjects with a history of coronary artery disease (any history of myocardial infarction or
      coronary revascularization) were also eligible for participation. Subjects were excluded if
      they had a history of congestive heart failure (any classification), unstable angina or acute
      coronary syndrome within the last 30 days, uncontrolled hypertension (blood pressure ≥
      170/100 mm/Hg), type 1 diabetes mellitus, uncontrolled type 2 diabetes mellitus (HbA1C ≥
      8.0%), history of gastrointestinal disease or surgery affecting absorption, peripheral
      arterial disease, diagnosis of active cancer (excluding squamous cell or basal cell skin
      cancer), current use of long-acting nitrate compounds such as isosorbide dinitrate or
      nitroglycerin, recent change in any medications (last 30 days), active plan to change diet or
      exercise patterns, history of hypersensitivity to any compound in the intervention or
      placebo, or history of intolerance to nitrates.

      Study Design The study was a double-blind, randomized crossover design to evaluate the
      effects of muscadine grape seed supplementation (Nature's Pearl 650 mg, two capsules daily.)
      The phytochemical profile of the supplement is presented in Table 1. The trial consisted of a
      screening visit followed by baseline and closeout visits for two study treatment periods (4
      weeks each), separated by a 4-week washout period (total of 5 visits over 14
      weeks).Endothelial function was assessed at the beginning and end of each study period using
      brachial artery flow-mediated dilation (brachial FMD - described below). A fasting blood
      sample was obtained at the open and close of each study period for measurement of lipids,
      inflammatory markers, and markers of antioxidant capacity and oxidative stress. Participants
      were asked to abstain from red wine, antioxidant vitamin supplements (including vitamin E,
      vitamin C, and beta-carotene supplements, more than 1 cup of black or green tea daily, and
      other grape seed supplements. Multivitamin supplements were permitted as long as they were
      taken for the study duration.

      Endothelial Function Study Protocol Details for the brachial FMD protocol, automated analysis
      and reproducibility have been published previously {Herrington 2001}. Briefly, subjects
      rested in a quiet, temperature-controlled room for 15 minutes. A standard (pediatric) cuff
      was placed on the right forearm 2 inches (5 cm) below the antecubital fossa. Once the
      transducer position was established over the left brachial artery, continuous scanning of the
      brachial artery was obtained for 2 minutes before the cuff occlusion, 4 minutes of cuff
      occlusion, and 2 minutes immediately after cuff release. Data were analyzed with an automated
      analysis system that determines changes in brachial artery diameter for 2 minutes after cuff
      release.

      Statistical Analysis The effects of supplementation with muscadine grape seeds and placebo
      were compared using paired t-tests and mixed linear models to take into account treatment
      order and period effects. The mixed linear models were also used to formally test for a
      residual effect of treatment in those subjects receiving active treatment in the first
      treatment period. Stratified analyses were performed to look for evidence of differential
      effects by age, gender, prevalent heart disease or heart disease risk factors. Nominal
      2-tailed p-values are presented for the primary outcome (percent change in brachial diameter)
      and for all secondary outcomes. All analyses were performed using SAS v. 9.1 (Cary, NC).
    

Intervention name(s): Muscadine grape seed supplement
Intervention type(s): Dietary Supplement
Intervention description(s): Nature's Pearl 650 mg, two capsules daily
Other intervention name(s): Nature's Pearl 650 mg, two capsules daily
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Other
Keywords: muscadine grapes; endothelial function