Mars Flavanol Exercise and Cognitive Function Study

• Sponsor: New York State Psychiatric Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT01180127
• Collaborator: Mars, Inc. (Industry)
• Enrollment: 41
• Arms: 4
• Duration (Months): 46

Study Details

Study Description

Brief Summary

This is a randomized controlled trial to test the impact of a flavonol containing food product and aerobic exercise on cognitive function and brain structure.

Condition or Disease	Intervention/Treatment	Phase
Cognitive Function	Dietary Supplement: Flavanol containing food product; Behavioral: Aerobic training; Dietary Supplement: Food product lacking flavanol; Behavioral: Wait list control	N/A

Detailed Description

1. Background and Significance A. The epidemiology of cognitive aging. Encompassing multiple cognitive domains, higher order thinking includes memory, language, abstract reasoning, and visuospatial ability. A range of studies have established that memory is a cognitive domain differentially targeted by the normal aging process. With an increase in lifespan and a decrease in co-morbid diseases, aging individuals expect to lead cognitively-challenging lives. Even mild forgetfulness, therefore, is no longer considered 'benign'. Indeed, with the exponential growth of the aging population, and since memory decline will occur in all of us as we age, age-related memory decline has emerged as a major societal problem.

1. The anatomy of cognitive aging. A range of studies in humans, non-human primates and rodents have established that the hippocampal formation, a brain circuit vital for memory, is targeted by the aging process. Age-related hippocampal dysfunction is therefore a major contributor to age-related memory decline.

The hippocampal formation is organized as a circuit, made up of separate but interconnected regions, including the entorhinal cortex, the dentate gyrus, the CA subfields, and the subiculum. Because of hippocampal circuit properties, dysfunction in one subregion will affect the function of neighboring subregions and the hippocampal circuit as a whole. Thus, when confronted with any process that causes the hippocampal circuit to malfunction, pinpointing the subregion that is most effected becomes an important goal.

In the case of age-related memory decline, a range of studies in humans, non-human primates, and rodents, have suggested that normal aging causes hippocampal dysfunction by differentially targeting the dentate gyrus.

1. Imaging cognitive aging. The anatomical organization of the hippocampal circuit and the differential vulnerability of the dentate gyrus to cognitive aging imposes specific requirements on brain imaging techniques. Specifically, an imaging technique must be able to assess the functional integrity of the multiple hippocampal subregions, in particular the dentate gyrus. With this in mind, our lab has been dedicated to optimizing a functional brain imaging approach applicable to both the human and rodent hippocampal formation. We have recently achieved this goal, and have been applying our cross-species imaging capabilities to investigate a range of process that affect hippocampal function.

2. Flavanols, exercise, and cognitive aging. Previous studies have established that physical exercise improved hippocampal function. We have recently exploited our cross-species imaging techniques to show, that within the hippocampal circuit, exercise has a selective effect on dentate gyrus function, in humans and in mice. Independently, a recent study has shown that the flavanol epichatechin improves hippocampal function, and importantly, within the hippocampal circuit, epichatechin was found to differentially target the dentate gyrus. Moreover, this study showed that epichatechin coupled with exercise had its greatest effect on dentate gyrus function.

3. Summary. Starting at around 30 years of age, all of us will begin experiencing the insidious cognitive slide of age-related memory decline. With the expansion of aging, age-related memory decline is swelling to epidemic proportions, and ameliorating age-related memory decline has emerged as major societal goal.

This proposal is designed to test the following hypothesis: That flavanols with or without physical exercise will ameliorate age-related memory decline. This hypothesis is informed by two sets of interleaving findings: First, a range of studies have pinpointed dysfunction in the dentate gyrus as a specific brain region contributing to age-related memory decline; and second, flavanol consumption with or without physical exercise enhances memory performance by improving dentate gyrus function.

In order to experimentally test this hypothesis an imaging technique is required that can assess the functional integrity of the dentate gyrus, techniques that are now available. Importantly, these imaging techniques have been developed so that can they can be applied not only to humans but also to animal models, generating the same 'imaging readout'. Cross-species imaging is particularly important for translational studies.

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Single (Investigator)
• Primary Purpose: Basic Science
• Official Title: Study of the Impact of a Flavanol Containing Food Product and Exercise on Cognitive Function and Brain Structure
• Study Start Date: Dec 1, 2009
• Actual Primary Completion Date: Oct 1, 2013
• Actual Study Completion Date: Oct 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: exercise, dietary intervention aerobic training and flavanol containing food product for 12 weeks	Dietary Supplement: Flavanol containing food product; 12 weeks, 2X/day, 20g serving; Behavioral: Aerobic training; 4X/week, 1 hour/session at 75% maximum HR
Active Comparator: no exercise, dietary intervention wait list control plus flavanol containing food product for 12 weeks	Dietary Supplement: Flavanol containing food product; 12 weeks, 2X/day, 20g serving; Behavioral: Wait list control; 12 week wait list control condition during which participants abstain from aerobic exercise
Active Comparator: exercise, food product lacking flavanol aerobic training plus food product without flavanol for 12 weeks	Behavioral: Aerobic training; 4X/week, 1 hour/session at 75% maximum HR; Dietary Supplement: Food product lacking flavanol; 20 g serving, 2X/day, food additive lacking flavonol
Placebo Comparator: wait list control food additive without flavanol wait list control plus food product without flavanol for 12 weeks	Dietary Supplement: Food product lacking flavanol; 20 g serving, 2X/day, food additive lacking flavonol; Behavioral: Wait list control; 12 week wait list control condition during which participants abstain from aerobic exercise

Outcome Measures

Primary Outcome Measures

1. CBV-fMRI (Cerebral Blood Volume-functional Magnetic Resonance Imaging) [Up to 12 weeks after exercise/dietary intervention exposure]

   In steady state conditions, CBV is an indirect measure of basal metabolism in the brain. CBV-fMRI is a technique that generates maps of basal metabolism across different brain regions

2. ModBent (Modified Benton Visual Retention Test) [Up to 12 weeks after exercise/dietary intervention exposure]

   This is an object recognition task. Participants view a complex stimulus, then are asked to select which one of two objects was identical to the studied stimulus. After a series of these matching trials, during the subsequent recognition trials participants are shown serially individual complex objects and asked to indicate whether the object was identical to any of the target stimuli viewed during the matching trials. Their reaction time for correct responses, measured in milliseconds, is the unit of measurement.

Secondary Outcome Measures

1. Modified Rey Auditory Verbal Learning Test [Up to 12 weeks after exercise/dietary intervention exposure]

   Participants are read a list of words over three learning trials and the subject is asked to free recall as many words as possible after each trial. These 3 trials are followed by 1 learning trial of a distracter list and then a short delayed free recall trial of the initial list. After approximately 60-minutes, subjects are asked to freely recall words from the initial list, then to recall words form the distracter list, and then complete a forced-choice recognition trial. A source memory trial is administered in which subjects are read each presented word and then asked to identify whether they were initially presented during the 3 learning trials or during the distracter trial. Measured as a retention score (ratio) for which the number of words recalled after the short delay is divided by the number of words recalled on the third learning trial.

2. VO2max [Up to 12 weeks after exercise/dietary intervention exposure]

   measured at randomization, i.e., before exposure to the intervention, and then again after completion of the 12-week intervention

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Age 50-75

2. English-speaking

3. Ambulatory

4. BMI < 32

5. Post-menopausal (women only), no estrogen replacement therapy

6. VO2max < 36 and 33 ml/kg/min for men age 50-59 and 60-69 respectively; < 29 and 27 ml/kg/min for women age 50-59 and 60-75 respectively.

7. Baecke Physical Activity Sports Score ≤ 2

8. Medical clearance to participate in the study (normal serum electrolyte, BUN, creatinine levels, normal blood pressure and resting cardiogram)

Exclusion Criteria:

1. Use of psychotropic medications

2. Current psychiatric disorder

3. Any condition for which aerobic training is counter-indicated

4. Habitual consumers of dietary or herbal supplements, including Gingko, flavonoid, and dietary herbal or plant extracts

5. Lactose Intolerance

6. Individuals who report directly to any of the study investigators

7. Diabetes

Exclusion Criteria (MRI-related)

1. Cardiac Pacemaker

2. Internal Pump

3. Insulin Pump

4. Tattoo eyeliner

5. Wire Sutures

6. Internal Metal Objects

7. Metal Slivers in Eye

8. Prosthesis

9. Hearing Aid Implants

10. Neurostimulator

11. Metal Fragments

12. Brain Aneurysm Clips

13. Vascular Clips

14. Breast Expander

15. Vena Cava Filter

16. Heart Valve

17. Metal Stents

18. Asthma

19. Hay-Fever

20. Sickle Cell Disease

21. Kidney Disease

22. Pregnant

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• New York State Psychiatric Institute
• Mars, Inc.

Investigators

• Principal Investigator: Scott A Small, MD, Columbia University

Study Documents (Full-Text)

None provided.

More Information

Publications

• Pereira AC, Huddleston DE, Brickman AM, Sosunov AA, Hen R, McKhann GM, Sloan R, Gage FH, Brown TR, Small SA. An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus. Proc Natl Acad Sci U S A. 2007 Mar 27;104(13):5638-43. Epub 2007 Mar 20.

• Responsible Party: Richard Sloan, Research Scientist, New York State Psychiatric Institute
• ClinicalTrials.gov Identifier: NCT01180127
• Other Study ID Numbers: 5804
• First Posted: Aug 11, 2010
• Last Update Posted: Dec 5, 2018
• Last Verified: Nov 1, 2018

• Keywords provided by Richard Sloan, Research Scientist, New York State Psychiatric Institute: flavonol; exercise; dentate gyrus; cerebral blood volume; dentate gyrus CBV

Study Results

Participant Flow

Arm/Group Title	Exercise, Dietary Intervention	no Exercise, Dietary Intervention	Exercise, Food Additive Lacking Flavanol	Wait List Control Food Additive Without Flavanol
Arm/Group Description	aerobic training and flavanol containing food product Flavanol containing food product: 12 weeks, 2X/day, 20g serving Aerobic training: 4X/week, 1 hour/session at 75% maximum HR	wait list control plus flavanol containing food product for 12 weeks Flavanol containing food product: 12 weeks, 2X/day, 20g serving Wait list control: 12 week wait list control condition during which participant abstain from aerobic exercise	aerobic training plus food additive without flavanol Aerobic training: 4X/week, 1 hour/session at 75% maximum HR Placebo food additive: 20 g serving, 2X/day, food additive lacking flavanol	12 weeks of wait list control status plus food additive without the flavanol containing food product Placebo food additive: 20 g serving, 2X/day, food additive lacking flavanol Wait list control: 12 week wait list control condition during which participant abstain from aerobic exercise
Period Title: Overall Study
STARTED	10	11	10	10
COMPLETED	8	11	9	9
NOT COMPLETED	2	0	1	1

Baseline Characteristics

Arm/Group Title	Exercise, Dietary Intervention	no Exercise, Dietary Intervention	Exercise, Food Additive Lacking Flavonol	Wait List Control Food Additive Without Flavonol	Total
Arm/Group Description	aerobic training and flavanol containing food product Flavanol containing food product: 12 weeks, 2X/day, 20g serving Aerobic training: 4X/week, 1 hour/session at 75% maximum HR	wait list control plus flavanol containing food product for 12 weeks Flavanol containing food product: 12 weeks, 2X/day, 20g serving Wait list control: 12 week wait list control condition during which participant abstain from aerobic exercise	aerobic training plus food additive without flavanol Aerobic training: 4X/week, 1 hour/session at 75% maximum HR Placebo food additive: 20 g serving, 2X/day, food additive lacking flavanol	12 weeks of wait list control status plus food additive without the flavanol containing food product Placebo food additive: 20 g serving, 2X/day, food additive lacking flavanol Wait list control: 12 week wait list control condition during which participant abstain from aerobic exercise	Total of all reporting groups
Overall Participants	10	11	10	10	41
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.4 (4.9)	57.5 (5.34)	56.6 (5.56)	56.6 (3.7)	57.5 (4.89)
Sex: Female, Male (Count of Participants)
Female	8 80%	7 63.6%	7 70%	7 70%	29 70.7%
Male	2 20%	4 36.4%	3 30%	3 30%	12 29.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 10%	2 18.2%	3 30%	4 40%	10 24.4%
Not Hispanic or Latino	9 90%	9 81.8%	7 70%	6 60%	31 75.6%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	1 10%	0 0%	0 0%	1 10%	2 4.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	1 10%	2 18.2%	2 20%	2 20%	7 17.1%
White	7 70%	6 54.5%	6 60%	4 40%	23 56.1%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	1 10%	3 27.3%	2 20%	3 30%	9 22%
Region of Enrollment (participants) [Number]
United States	10 100%	11 100%	10 100%	10 100%	41 100%

Outcome Measures

1. Primary Outcome

Title	CBV-fMRI (Cerebral Blood Volume-functional Magnetic Resonance Imaging)
Description	In steady state conditions, CBV is an indirect measure of basal metabolism in the brain. CBV-fMRI is a technique that generates maps of basal metabolism across different brain regions
Time Frame	Up to 12 weeks after exercise/dietary intervention exposure

Outcome Measure Data

Analysis Population Description

One subject in the exercise, food additive lacking flavanol arm, and one subject in the wait list control food additive without flavanol arm had non useable data for this outcome which is why there are only 8 subjects analyzed in those two arms rather than 9.

Arm/Group Title	Exercise, Dietary Intervention	no Exercise, Dietary Intervention	Exercise, Food Additive Lacking Flavanol	Wait List Control Food Additive Without Flavanol
Arm/Group Description	aerobic training and flavanol containing food product Flavanol containing food product: 12 weeks, 2X/day, 20g serving Aerobic training: 4X/week, 1 hour/session at 75% maximum HR	wait list control plus flavanol containing food product for 12 weeks Flavanol containing food product: 12 weeks, 2X/day, 20g serving Wait list control: 12 week wait list control condition during which participant abstain from aerobic exercise	aerobic training plus food additive without flavanol Aerobic training: 4X/week, 1 hour/session at 75% maximum HR Placebo food additive: 20 g serving, 2X/day, food additive lacking flavanol	12 weeks of wait list control status plus food additive without the flavanol containing food product Placebo food additive: 20 g serving, 2X/day, food additive lacking flavanol Wait list control: 12 week wait list control condition during which participant abstain from aerobic exercise
Measure Participants	8	11	8	8
Baseline	3.43 (1.43)	2.55 (0.45)	2.89 (0.70)	3.38 (0.52)
12 weeks	4.58 (1.66)	4.48 (1.31)	2.91 (0.81)	2.60 (0.59)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exercise, Dietary Intervention, no Exercise, Dietary Intervention, Exercise, Food Additive Lacking Flavanol, Wait List Control Food Additive Without Flavanol
	Comments	Repeated measures ANOVA for the interaction of time (baseline vs 12 week) and flavanol group.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.0001
	Comments
	Method	Repeated measures ANOVA
	Comments

2. Primary Outcome

Title	ModBent (Modified Benton Visual Retention Test)
Description	This is an object recognition task. Participants view a complex stimulus, then are asked to select which one of two objects was identical to the studied stimulus. After a series of these matching trials, during the subsequent recognition trials participants are shown serially individual complex objects and asked to indicate whether the object was identical to any of the target stimuli viewed during the matching trials. Their reaction time for correct responses, measured in milliseconds, is the unit of measurement.
Time Frame	Up to 12 weeks after exercise/dietary intervention exposure

Outcome Measure Data

Analysis Population Description

One subject in the exercise, dietary intervention and one subject in the no exercise, dietary intervention group had outlying (larger than 3 standard deviation from mean) ModBent values that were deleted and hence those groups have 7 and 10 subjects analyzed rather than 8 and 11 respectively.

Arm/Group Title	Exercise, Dietary Intervention	no Exercise, Dietary Intervention	Exercise, Food Additive Lacking Flavonol	Wait List Control Food Additive Without Flavonol
Arm/Group Description	aerobic training and flavonol containing food product Flavonol containing food product: 12 weeks, 2X/day, 20g serving Aerobic training: 4X/week, 1 hour/session at 75% maximum HR	wait list control plus flavonol containing food product for 12 weeks Flavonol containing food product: 12 weeks, 2X/day, 20g serving Wait list control: 12 week wait list control condition during which participant abstain from aerobic exercise	aerobic training plus food additive without flavonol Aerobic training: 4X/week, 1 hour/session at 75% maximum HR Placebo food additive: 20 g serving, 2X/day, food additive lacking flavonol	12 weeks of wait list control status plus food additive without the flavonol containing food product Placebo food additive: 20 g serving, 2X/day, food additive lacking flavonol Wait list control: 12 week wait list control condition during which participant abstain from aerobic exercise
Measure Participants	7	10	9	9
Baseline	1945 (584)	2296 (1056)	2291 (515)	2347 (919)
12 weeks	1867 (478)	2009 (815)	2560 (1086)	2794 (1298)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exercise, Dietary Intervention, no Exercise, Dietary Intervention, Exercise, Food Additive Lacking Flavanol, Wait List Control Food Additive Without Flavanol
	Comments	ANCOVA used to test main effect of flavanol
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.038
	Comments	The ANCOVA model included a main effect for both flavanol and exercise, so this p-value is for the effect of flavanol on Modbent controlling for baseline Modbent and exercise
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exercise, Dietary Intervention, no Exercise, Dietary Intervention, Exercise, Food Additive Lacking Flavanol, Wait List Control Food Additive Without Flavanol
	Comments	ANCOVA used to test main effect of exercise
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.815
	Comments	The ANCOVA included both a main effect for flavanol and exercise, so this p-value is for the test of exercise controlling for baseline Modbent and flavanol
	Method	ANCOVA
	Comments

3. Secondary Outcome

Title	Modified Rey Auditory Verbal Learning Test
Description	Participants are read a list of words over three learning trials and the subject is asked to free recall as many words as possible after each trial. These 3 trials are followed by 1 learning trial of a distracter list and then a short delayed free recall trial of the initial list. After approximately 60-minutes, subjects are asked to freely recall words from the initial list, then to recall words form the distracter list, and then complete a forced-choice recognition trial. A source memory trial is administered in which subjects are read each presented word and then asked to identify whether they were initially presented during the 3 learning trials or during the distracter trial. Measured as a retention score (ratio) for which the number of words recalled after the short delay is divided by the number of words recalled on the third learning trial.
Time Frame	Up to 12 weeks after exercise/dietary intervention exposure

Outcome Measure Data

Analysis Population Description

There were 4 subjects (1 in exercise, dietary intervention; 2 in no exercise, dietary intervention, and 1 in exercise, food additive lacking flavanol) who did not have useable data and are thus not included in analyses.

Arm/Group Title	Exercise, Dietary Intervention	no Exercise, Dietary Intervention	Exercise, Food Additive Lacking Flavanol	Wait List Control Food Additive Without Flavanol
Arm/Group Description	aerobic training and flavanol containing food product Flavanol containing food product: 12 weeks, 2X/day, 20g serving Aerobic training: 4X/week, 1 hour/session at 75% maximum HR	wait list control plus flavanol containing food product for 12 weeks Flavanol containing food product: 12 weeks, 2X/day, 20g serving Wait list control: 12 week wait list control condition during which participant abstain from aerobic exercise	aerobic training plus food additive without flavanol Aerobic training: 4X/week, 1 hour/session at 75% maximum HR Placebo food additive: 20 g serving, 2X/day, food additive lacking flavanol	12 weeks of wait list control status plus food additive without the flavanol containing food product Placebo food additive: 20 g serving, 2X/day, food additive lacking flavanol Wait list control: 12 week wait list control condition during which participant abstain from aerobic exercise
Measure Participants	7	9	8	9
Baseline	0.76 (0.21)	0.69 (0.19)	0.80 (0.19)	0.89 (0.11)
12 weeks	0.83 (0.08)	0.65 (0.25)	0.76 (0.23)	0.87 (0.21)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exercise, Dietary Intervention, no Exercise, Dietary Intervention, Exercise, Food Additive Lacking Flavanol, Wait List Control Food Additive Without Flavanol
	Comments	ANCOVA for testing main effect of flavanol
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.853
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exercise, Dietary Intervention, no Exercise, Dietary Intervention, Exercise, Food Additive Lacking Flavanol, Wait List Control Food Additive Without Flavanol
	Comments	ANCOVA for testing main effect of exercise
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.581
	Comments
	Method	ANCOVA
	Comments

4. Secondary Outcome

Title	VO2max
Description	measured at randomization, i.e., before exposure to the intervention, and then again after completion of the 12-week intervention
Time Frame	Up to 12 weeks after exercise/dietary intervention exposure

Outcome Measure Data

Analysis Population Description

One subject in the exercise, dietary intervention and one subject in the exercise, food additive lacking flavanol group had unusable data for this outcome and thus are not included in these analyses.

Arm/Group Title	Exercise, Dietary Intervention	no Exercise, Dietary Intervention	Exercise, Food Additive Lacking Flavanol	Wait List Control Food Additive Without Flavanol
Arm/Group Description	aerobic training and flavanol containing food product Flavanol containing food product: 12 weeks, 2X/day, 20g serving Aerobic training: 4X/week, 1 hour/session at 75% maximum HR	wait list control plus flavanol containing food product for 12 weeks Flavanol containing food product: 12 weeks, 2X/day, 20g serving Wait list control: 12 week wait list control condition during which participant abstain from aerobic exercise	aerobic training plus food additive without flavanol Aerobic training: 4X/week, 1 hour/session at 75% maximum HR Placebo food additive: 20 g serving, 2X/day, food additive lacking flavanol	12 weeks of wait list control status plus food additive without the flavanol containing food product Placebo food additive: 20 g serving, 2X/day, food additive lacking flavanol Wait list control: 12 week wait list control condition during which participant abstain from aerobic exercise
Measure Participants	7	11	8	9
Baseline	25.6 (3.77)	26.26 (4.62)	25.1 (4.36)	23.94 (3.81)
12 weeks	27.8 (4.33)	25.36 (3.66)	25.98 (6.57)	25.44 (5.51)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Exercise, Dietary Intervention, no Exercise, Dietary Intervention, Exercise, Food Additive Lacking Flavanol, Wait List Control Food Additive Without Flavanol
	Comments	ANCOVA was used to test for an exercise effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.237
	Comments
	Method	ANCOVA
	Comments

Adverse Events

Arm/Group Title	Exercise, Dietary Intervention		no Exercise, Dietary Intervention		Exercise, Food Additive Lacking Flavonol		Wait List Control Food Additive Without Flavonol
Arm/Group Description	aerobic training and flavanol containing food product Flavanol containing food product: 12 weeks, 2X/day, 20g serving Aerobic training: 4X/week, 1 hour/session at 75% maximum HR		wait list control plus flavanol containing food product for 12 weeks Flavanol containing food product: 12 weeks, 2X/day, 20g serving Wait list control: 12 week wait list control condition during which participant abstain from aerobic exercise		aerobic training plus food additive without flavanol Aerobic training: 4X/week, 1 hour/session at 75% maximum HR Placebo food additive: 20 g serving, 2X/day, food additive lacking flavanol		12 weeks of wait list control status plus food additive without the flavanol containing food product Placebo food additive: 20 g serving, 2X/day, food additive lacking flavanol Wait list control: 12 week wait list control condition during which participant abstain from aerobic exercise
All Cause Mortality
	Exercise, Dietary Intervention		no Exercise, Dietary Intervention		Exercise, Food Additive Lacking Flavonol		Wait List Control Food Additive Without Flavonol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Exercise, Dietary Intervention		no Exercise, Dietary Intervention		Exercise, Food Additive Lacking Flavonol		Wait List Control Food Additive Without Flavonol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/11 (0%)		0/10 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Exercise, Dietary Intervention		no Exercise, Dietary Intervention		Exercise, Food Additive Lacking Flavonol		Wait List Control Food Additive Without Flavonol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/11 (0%)		0/10 (0%)		0/10 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.