Cocoa Flavanol Intake and Exercise in Hypoxia

Study Overview
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Brief Summary
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Not uncommonly, sports events take place or finish at high altitude, where physical and cognitive (e.g. decision-making, motor control) performance in hypoxia is determining the outcome of sports performance. With nutritional supplements growing in popularity in the athletic and non-athletic population, research is increasingly focussing on dietary constituents which can improve cognitive and exercise performance. Flavonoids, a subgroup of polyphenols, are a class of natural compounds found in the human diet and include subcategories of flavanols, flavonols, iso-flavones, flavones, and anthocyanidins. Intake of flavanols, found in grapes, tea, red wine, apples and especially cocoa, causes an nitric oxide (NO)-mediated vasodilatation and can improve peripheral and cerebral blood flow (CBF). For cocoa flavanol (CF), there is evidence that both long term and acute intake can improve cognitive function, with the quantity and bioavailability of the consumed CF highly influencing its beneficial effects and with higher doses eliciting greater effects on cognition. Increased CBF following acute and chronic (3 months) CF intake has been demonstrated in healthy young subjects. Moreover, cognitive performance and mood during sustained mental efforts are improved after acute CF intake in healthy subjects and CF intake can increase prefrontal oxygenation during cognitive tasks in well-trained athletes. Moreover, CF intake is not only associated with an improved blood flow, but it might also improve exercise performance following 2 weeks of dark chocolate intake. On top of that, CF is known to have anti-oxidant properties and 2 week CF intake has been associated with reduced oxidative-stress markers following exercise. In hypoxic conditions, arterial pressure of oxygen (PaO2) and arterial saturation of O2 (SaO2) are decreased, compromising tissue oxygen delivery. Since brain function and brain integrity are dependent on continuous oxygen supply, brain desaturation may result in an impaired cognitive function in hypoxia. The severity of the impairment is related to the extent of high altitude, with at 3000m (=14.3 % oxygen (O2); = 71% of oxygen available at sea level) psychomotor impairments being visible. Cerebral oxygenation, which can be measured by Near-infrared spectroscopy, is lowered in hypoxia. It remains unclear whether CF intake can influence cerebral oxygenation and perfusion in hypoxic conditions and whether CF intake could (partially) counteract hypoxia-induced cognitive impairments. Therefore, the first aim of this study was to investigate whether cognitive function and prefrontal oxygenation during a mental demanding task will be impaired by hypoxic conditions (3000m altitude; 14.3% O2) and whether these impairments can be partially restored by subchronic CF intake (7 days, 900 mg/day). Hypoxia also impairs physical performance. Hypoxia-induced reductions in cerebral oxygenation may favour central fatigue, i.e. the failure of the central nervous system to excite the motoneurons adequately, hence impairing exercise performance in hypoxic conditions. Since hypoxia also impairs oxygen delivery to muscle tissue, the decreased oxygen supply to and impaired oxidative energy production in the exercising muscle is a second factor negatively affecting exercise performance. Besides the aforementioned effects of altitude on O2 delivery, hypoxia also results in increased oxidative stress. Oxidative stress refers to the imbalance between prooxidant and antioxidant levels in favor of prooxidants in cells and tissues and can result from diminished antioxidant levels or increased production of reactive oxygen species. The latter can be induced by both exhaustive exercise and high altitude. Since oxidative stress can be counteracted by CF, we also aim to investigate how markers of oxidative stress can be affected by CF intake by exercise in hypoxia. Therefore, the second aim of this study was to investigate possible beneficial effects of CF intake on changes in cerebral and muscle vasoreactivity and oxidative stress during exercise in hypoxia and its implications on exercise performance.

Official Title
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The Effect of Cocoa Flavanol Intake on Cerebral and Muscle Perfusion and Oxygenation in Hypoxia - Implications for Cognitive and Exercise Performance

Conditions
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Hypoxia, Altitude

Intervention / Treatment
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* Dietary Supplement: cocoa flavanol
* Dietary Supplement: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: train more than 10 hours/week Exclusion Criteria: severe head injuries in the past hypertensive with cardiovascular disease / take medication for cardiovascular disease smokers take nutritional supplements had stayed at high altitude (>3000m) for 3 weeks during the last 6 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 36 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Hypoxia Cocoa flavanol<br>Exercise or cognitive test in (acute) hypoxic condition after 7 days of cocoa flavanol intake | Dietary Supplement: cocoa flavanol<br>* 7 days intake of cocoa flavanol supplement (naturex)<br>|
| Placebo Comparator: Hypoxia Placebo<br>Exercise or cognitive test in (acute) hypoxic condition after 7 days of placebo intake | Dietary Supplement: placebo<br>* 7 days of placebo intake<br>|
| Active Comparator: Normoxia Cocoa flavanol<br>Exercise or cognitive test in normoxic condition after 7 days of cocoa flavanol intake | Dietary Supplement: cocoa flavanol<br>* 7 days intake of cocoa flavanol supplement (naturex)<br>|
| Placebo Comparator: normoxia placebo<br>Exercise or cognitive test in normoxic condition after 7 days of placebo intake | Dietary Supplement: placebo<br>* 7 days of placebo intake<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| prefrontal/muscular oxygenation |  | change from baseline (pre-exercise) at post-exercise after 7 days of intake | 
| work (kj) performed during 20 minute time trial |  | after 7 days of intake | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Flow mediated dilation |  | after 6 days of intake | 
| oxidative stress |  | change from baseline (pre-exercise) at post-exercise after 7 days of intake |