Date of Award
Master of Science (MS)
blood flow, cognitive function, hypoxia, Nitrate
Medicine and Health Sciences
Acute high altitude (HA) exposure compromises cognitive function thus posing a significant risk to personnel safety in a HA environment, particularly when performing tasks that requires cognitive vigilance. Normal cerebral function, and thus cognitive function, is dependent upon oxygen supply. At HA there is reduced oxygen availability results in compensatory increases in cerebrovascular blood flow which may be related to nitric oxide (NO), a primary signaling molecule that acts to increase blood flow and ensure an optimal neurovascular coupling (NVC). Upon initial ascent to HA, however, there may be reductions in NO production which may play a role in acute decrements in cerebrovascular/cognitive function at HA. Dietary nitrate may serve as a means to replenish NO availability. Increasing NO in this manner could have positive effects on NVC during increased cognitive demand. Purpose: To investigate the effects of acute nitrate supplementation on 1) cognitive and 2) cerebrovascular function compared to an inert placebo at HA. Hypotheses: It was hypothesized that compared to placebo at HA, nitrate supplementation would 1) increase cognitive function, and 2) increase cerebral blood flow. Methods: 20 healthy men (23 ± 3 yrs, BMI 24.3 ± 3.0 kg∙m-2) participated in this randomized, double-blind, crossover design study on two separate days. Following sea level (SL) cognitive/NVC testing, participants consumed either nitrate (NIT) or a NIT-depleted placebo (PLA). Participants then underwent 120 minutes of HA (11.5 ± 0.2% O2) and all cognitive/NVC testing was repeated. NVC was assessed by measuring the change in mean middle cerebral artery (MCA) and common carotid artery (CCA) blood flow during a cognitive challenge (incongruent Stroop task) using Doppler ultrasound. Brachial artery flow-mediated dilation (FMD), salivary nitrite, and exhaled NO (in a subset of participants) were assessed as systemic proxies of NO-metabolism. A computerized testing battery was used to assess cognitive function across a variety of cognitive domains including memory, executive function, cognitive flexibility, sensorimotor, and attention. Results: Salivary nitrite and exhaled NO significantly increased following supplementation at HA for NIT compared to PLA (p < 0.05). FMD significantly decreased and MCA and CCA blood flow increased at HA in both conditions (p < 0.05). Measures of NVC were unchanged at HA in both conditions. Memory performance significantly decreased at HA in both conditions (p < 0.05), while all other domains were unaffected. Conclusions: NIT significantly increased markers of NO-metabolism at HA compared to PLA. Cerebrovascular blood flow increased at HA compared to SL in both conditions at rest. NIT, however, was unable to prevent reductions in FMD or memory at HA nor was NIT able to augment NVC at HA compared to SL.
Lefferts, Wesley K., "Effects of Nitrate Supplementation on Cognitive and Cerebrovascular Function at Simulated High Altitude" (2014). Theses - ALL. 73.