Effects of Dark Chocolate on Insulin Sensitivity in People With High Blood Pressure
Condition: Hypertension
MeSH terms: Hypertension; Insulin Resistance
Study type: Interventional
Phase: Phase 1

Summary: 
      This study will examine whether dark chocolate affects the way patients with hypertension
      (high blood pressure) respond to insulin, a hormone secreted by the pancreas that regulates
      blood glucose (sugar) levels. In many people with hypertension, insulin is not as effective
      in helping the body use glucose. This is called insulin resistance. Insulin also increases
      blood flow into muscle by opening inactive blood vessels. Laboratory studies suggest that
      eating dark chocolate may improve blood pressure. This study will determine whether dark
      chocolate improves insulin resistance or changes how blood vessels react to insulin in
      hypertensive people.

      People between 21 and 65 years of age who have high blood pressure and are not pregnant may
      be eligible for this study. Candidates are screened with a medical history, physical
      examination, and blood and urine tests.

      Participants refrain from eating foods containing chocolate or cocoa for 1 week and then come
      to the clinic on three separate occasions 3 weeks apart for a glucose clamp test and contrast
      ultrasound, described below. At the first glucose clamp test, subjects are randomly assigned
      to drink either a cocoa drink with high anti-oxidant content or one with a very low content
      of anti-oxidant. Each drink will be taken twice a day for 2 weeks. At the end of the 2 weeks,
      they return for a second glucose clamp test. At the second test, they stop taking the cocoa
      drink for 1 week and then start again for another 2 weeks. For this 2-week period, those who
      were given the high anti-oxidant content cocoa drink the first 2 weeks will take the placebo,
      very low anti-oxidant drink this time, and those who took the placebo will now have the high
      anti-oxidant cocoa drink. After this 2 weeks of taking the cocoa drink or placebo, they then
      take the third and last glucose clamp test.

      Glucose clamp test: This test measures how the body responds to insulin. Subjects fast the
      night before each test and do not eat until the test is over, usually in the early afternoon.
      For the test, the subject lies in a bed or reclines in a chair. A needle is placed in a vein
      in each arm - one for collecting blood samples and the other for infusing glucose, insulin,
      and a potassium solution. Blood glucose and insulin levels are measured frequently during the
      test and the rate of the glucose infusion is adjusted to keep blood glucose at the baseline
      (fasting) level. Blood samples are tested for blood count, electrolytes, liver function...
    

Detailed description: 
      Dark chocolate and other cocoa products contain antioxidants including the polyphenol
      epicatechin that have beneficial effects on vascular function. Oral consumption of dark
      chocolate lowers blood pressure in elderly subjects with isolated systolic hypertension while
      drinking cocoa acutely improves flow-mediated vasodilation in subjects with cardiovascular
      risk factors. Work from our lab and elsewhere has shown that regulation of hemodynamic and
      metabolic homeostasis are coupled such that subjects with essential hypertension are also
      insulin resistant. Therefore, we hypothesize that cocoa consumption will improve both blood
      pressure and insulin sensitivity in subjects with essential hypertension. To test this
      hypothesis, we will conduct a randomized double-blind, crossover study in subjects with
      essential hypertension to evaluate the effects of cocoa versus placebo on blood pressure,
      insulin sensitivity, and insulin-mediated capillary recruitment in skeletal muscle. After a 7
      day cocoa-free run-in period, subjects will be randomized to receive 15 consecutive daily
      doses of either cocoa drink (150 ml twice a day with a total of 900 mg of polyphenols and 237
      kcal) or polyphenol poor placebo drink (150 ml twice a day with a total of 36 mg of
      polyphenols and 234 kcal). After the 15 day treatment period, the subjects will enter a 1
      week cocoa-free washout period followed by cross-over to the other treatment. Subjects will
      be counseled to maintain an isocaloric diet during the study. Blood pressure, insulin
      sensitivity, and insulin-mediated capillary recruitment will be assessed in each subject
      after the run-in period, after 15 days of treatment, and after completion of the cross-over.
      Blood pressure will also be measured every Monday, Wednesday, and Friday for the duration of
      the study. Insulin sensitivity will be measured using the hyperinsulinemic euglycemic glucose
      clamp technique. Insulin-stimulated capillary recruitment in forearm skeletal muscle will be
      measured by ultrasound with "microbubble" contrast during the glucose clamp studies. Peak and
      trough plasma epicatechin levels will be measured prior to each glucose clamp study using an
      HPLC assay. This study will determine if short-term oral administration of cocoa is effective
      at lowering blood pressure, improving insulin sensitivity, and restoring vascular function in
      subjects with essential hypertension. This is highly relevant to major public health problems
      such as diabetes, obesity, hypertension, and cardiovascular diseases where insulin resistance
      and vascular dysfunction are important pathophysiological components.
    

Intervention name(s): Effects of dark chocolate
Intervention type(s): Behavioral
Primary purpose: Treatment
Keywords: Epicatechin; Polyphenols; Chocolate; Insulin Resistance; Endothelial Dysfunction; Hypertension