Role of Flavanols In Cardiovascular Function in Healthy Aging
| Status: | Completed |
|---|---|
| Conditions: | Healthy Studies |
| Therapuetic Areas: | Other |
| Healthy: | No |
| Age Range: | 18 - 80 |
| Updated: | 4/21/2016 |
| Start Date: | September 2011 |
| End Date: | May 2014 |
Effects of Dietary Flavanols on Cutaneous, Peripheral, and Cerebral Vascular Function in Young and Old Humans
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.
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.
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.
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.
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
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