Role of Flavanols In Cardiovascular Function in Healthy Aging
Condition: Aging
Study type: Interventional

Summary: 
      Groups of naturally occurring compounds called flavonoids are found in foods such as fruits
      and vegetables, red wine, tea, dark chocolate and cocoa products. Diets rich in flavonoids
      are associated with decreased risk for cardiovascular disease and major cardiovascular events
      (i.e. myocardial infarction) and have been shown to improve blood pressure, insulin
      sensitivity, and vascular function in a variety populations (Type II diabetes, elderly,
      smokers, etc.). The presumed beneficial effects of these compounds are thought to act through
      their inherent ability to scavenge free radicals. Specifically flavonoids scavenge superoxide
      anions which are free radicals that react with nitric oxide (NO) to produce peroxynitrite.
      The formation of peroxynitrite ultimately reduces the bioavailability of NO which is
      essential for vasodilation and thus vascular health and function. Normal aging is associated
      with impaired endothelial function, which presumably is due to less than optimal levels of NO
      bioavailability. Therefore, interventions that can increase NO bioavailability would be
      expected to improve microvascular function and vascular health in this population. The
      purpose of this study is to investigate the effects of dietary flavonoid supplementation on
      the vasodilatory capacity of the cutaneous vasculature, as well as on cerebral vascular
      reactivity and arterial stiffness in young and old humans. This study will test the
      hypothesis that acute dietary flavonoid treatment will improve impaired cutaneous
      vasodilatory capacity, cerebral vasomotor reactivity, and reduce arterial stiffness in older
      but not young humans.
    

Detailed description: 
      Role of nitric oxide in vascular function. Nitric oxide (NO) is an important signaling
      molecule involved in many physiological processes. Of particular interest is its role in
      endothelial function and blood flow regulation. In response to heat or sheer stress against
      the walls of blood vessels, the endothelial layer of blood vessels releases NO, which causes
      smooth muscle in the vessel wall to relax and the vessel to dilate. Environmental heat-stress
      leads to an increase in skin blood flow to allow for improved heat loss from the body surface
      to the environment, and relies on NO. Normal aging reduces NO bioavailability leading to an
      impaired ability to increase skin blood flow in response to environmental heat-stress.
      Additionally, cerebral blood flow is reduced and arterial stiffness is increased in the
      normal aging process which is at least partially attributed to reductions in NO
      bioavailability.

      Effects of dietary flavonoids. As previously mentioned Flavonoids are a group of natural
      compounds found in vegetables, fruits, wine, tea, and cocoa. Flavanols are a subfamily of
      flavonoids, and are quantitatively the most important compound in flavonoid family in western
      diets. Flavanol intake has been shown to improve vascular health, as well as increase insulin
      sensitivity, decrease blood pressure, reduce platelet aggregation, and enhance cerebral blood
      flow. The basic chemical features of flavanol allows them to act as classic antioxidants to
      scavenge free-radicals decreasing oxidant level in cells. High levels of free radicals,
      especially superoxide, can reduce the bioavailability of NO and thus any NO-mediated actions.
      Cocoa and cocoa products are potent sources of flavanols, and therefore have been used
      extensively as a dietary intervention to study the effects of flavanol supplementation on
      various disease states.

      Impairments in vascular health in the normal aging process. The ability to increase skin
      blood flow in response to environmental heat-stress is lost with normal aging, especially
      when individuals exceed 65 years of age. An attenuated skin blood flow response during
      exposure to environmental heat stress would place these older individuals at an increased
      risk for heat-related illness or death. The ability to raise skin blood flow with rising skin
      temperature has been demonstrated to have a large nitric oxide component, so a deficit in NO
      bioavailability, which is also consistently observed in aging populations, could presumably
      lead to the attenuated skin blood flow response to heat stress. Furthermore, it is well
      documented that cerebral blood flow is reduced while arterial stiffness is increased in the
      normal aging process. In regard to the reduction in NO in aging populations, flavanol
      supplementation has been shown to decrease production of free radicals, which can scavenge
      and reduce NO levels thereby improving indices of vascular health including flow mediated
      vasodilation. Therefore, flavanol supplementation may maintain NO bioavailability at optimal
      levels, and provide a feasible way for aging populations to maintain vascular health and
      prevent heat-related illness and death.

      Significance:

      This study will address the mechanisms of impaired cutaneous and cerebral blood flow as well
      as increased arterial stiffness that can occur in aging populations. Furthermore, if the
      hypothesis is correct, findings from this study will provide evidence for the efficacy of
      flavanols to be used (as a simple and safe lifestyle intervention) to reverse or combat
      impaired vascular function that commonly occurs in older individuals.
    

Intervention name(s): High Flavanol first then Low Flavanol; Low Flavanol first then High Flavanol
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): The high flavanol trial will be performed following consumption of a beverage containing 1,050 mg of commercially available Cocoa Flavanols which will be mixed into 250 ml of distilled water. The subjects will consume this beverage and measurements will be performed 2 hours after consumption. The low flavanol trial will be performed following consumption of a beverage containing 0 mg of Cocoa Flavanols which will be mixed into 250 ml of distilled water. The subjects will consume this beverage and measurements will be performed 2 hours after consumption.; The low flavanol trial will be performed following consumption of a beverage containing 0 mg of Cocoa Flavanols which will be mixed into 250 ml of distilled water. The subjects will consume this beverage and measurements will be performed 2 hours after consumption. The high flavanol trial will be performed following consumption of a beverage containing 1,050 mg of commercially available Cocoa Flavanols which will be mixed into 250 ml of distilled water. The subjects will consume this beverage and measurements will be performed 2 hours after consumption.
Other intervention name(s): dark chocolate beverage; chocolate; Mars Incorporated
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: Nitric Oxide; Vascular Function; Aging; Blood Pressure; Arterial Stiffness; Cardiovascular Disease; Cerebral Blood Flow