Role of Flavanols In Cardiovascular Function in Healthy Aging

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Robert M. Brothers, University of Texas at Austin
ClinicalTrials.gov Identifier:
NCT01395277
First received: July 13, 2011
Last updated: May 20, 2014
Last verified: May 2014
  Purpose

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 vasomotor 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.


Condition Intervention
Aging
Dietary Supplement: CocoaVia Dark Chocolate Flavored Drink
Dietary Supplement: Placebo Trial: CocoaVia Dark Chocolate Flavored Drink

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single Blind (Subject)
Primary Purpose: Basic Science
Official Title: Effects of Dietary Flavanols on Cutaneous, Peripheral, and Cerebral Vascular Function in Young and Old Humans

Further study details as provided by University of Texas at Austin:

Primary Outcome Measures:
  • Cutaneous blood flow response to local heating of the skin. [ Time Frame: prior to (baseline) and 2 hours post beverage consumption ] [ Designated as safety issue: No ]
    Local heating of the cutaneous vasculature to 42 degree C is commonly used to evoke a maximal skin blood flow response (only at the site of local heating). This response is almost entirely dependent on nitric oxide mediated vasodilation.


Secondary Outcome Measures:
  • Pulse Wave Velocity / Arterial Stiffness [ Time Frame: Prior to (baseline) and 2 hours following beverage consumption ] [ Designated as safety issue: No ]
    Assessment of pulse wave velocity in the common carotid artery and the femoral artery provides an index of arterial stiffness.


Enrollment: 45
Study Start Date: September 2011
Study Completion Date: May 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Experimental Trial: High Flavanol Trial
The measurements will be made on all study participants on two separate occasions; 1) before and 2 hours following consumption of a beverage with "high" flavanol content (experimental trial), and 2) before and 2 hours following consumption of a beverage with "low" flavanol content (placebo trial).
Dietary Supplement: CocoaVia Dark Chocolate Flavored Drink
The experimental trial (high flavanol group) will be performed following consumption of a beverage containing 1,050 mg of Cocoa Flavanols. This cocoa flavanol powder will be purchased from Mars Incorporated (Hackettstown, New Jersey) and 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 Names:
  • chocolate
  • Mars Incorporated
Placebo Comparator: Placebo Trial: Low Flavanol Trial
The measurements will be made on all study participants on two separate occasions; 1) before and 2 hours following consumption of a beverage with "high" flavanol content (experimental trial), and 2) before and 2 hours following consumption of a beverage with "low" flavanol content (placebo trial).
Dietary Supplement: Placebo Trial: CocoaVia Dark Chocolate Flavored Drink
The placebo trial (low flavanol content) will be performed following consumption of a beverage containing 75 mg of Cocoa Flavanols. This cocoa flavanol powder will be purchased from Mars Incorporated (Hackettstown, New Jersey) and 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 Names:
  • chocolate
  • Mars Incorporated

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 of 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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Males and Females between 18 - 26 years old
  • Males and Females between 65 - 80 years old

Exclusion Criteria:

  • cardiovascular disease
  • metabolic disease
  • neurological disease
  • Pregnant lady
  • Current smoker (or regularly smoked within last year)
  • Currently taking medications known to effect the autonomic nervous system
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01395277

Locations
United States, Texas
University of Texas at Austin: Environmental and Autonomic Physiolgy Laboratory
Austin, Texas, United States, 78712
Sponsors and Collaborators
University of Texas at Austin
Investigators
Principal Investigator: R. Matthew Brothers, PhD University of Texas at Austin
  More Information

No publications provided

Responsible Party: Robert M. Brothers, Assistant Professor, University of Texas at Austin
ClinicalTrials.gov Identifier: NCT01395277     History of Changes
Other Study ID Numbers: 2011-05-0029
Study First Received: July 13, 2011
Last Updated: May 20, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Texas at Austin:
Nitric Oxide
Vascular Function
Aging
Blood Pressure
Arterial Stiffness
Cardiovascular Disease
Cerebral Blood Flow

ClinicalTrials.gov processed this record on October 02, 2014