Tactical aviators rely on elevated inspired oxygen concentrations (hyperoxia) to mitigate risks associated with hypoxia and decompression stress; however, hyperoxia can negatively impact cerebral physiology by reducing cerebral blood flow (CBF). This study sought to characterize the relationship between fraction of inspired oxygen (FiO₂) and CBF, and to identify the threshold at which reductions in cerebral perfusion occur. Healthy participants underwent MRI-based arterial spin labeling while exposed to stepwise increases in FiO₂ ranging from 30% to 100%. The results demonstrated that lower levels of hyperoxia (≤50% FiO₂) did not significantly affect CBF, whereas higher levels (≥60% FiO₂) produced significant reductions in cerebral perfusion in a clear dose-dependent manner. Exposure to 100% FiO₂ resulted in the greatest reductions, but importantly, CBF returned to baseline levels once subjects were returned to normoxic conditions (21% FiO₂). Overall, these findings establish a threshold near 60% FiO₂ at which hyperoxia begins to impair cerebral perfusion, highlighting the importance of optimizing oxygen delivery strategies in aviation environments to balance protection from hypoxia while minimizing unintended reductions in brain blood flow.

Damato, et al. Int J Mol Sci (2024).

Funding Source: Department of Defense, Naval Medical Research Center, N3239819P0321

Tactical aviators require administration of enhanced inspired oxygen concentrations (hyperoxia) to reduce risk of hypobaric hypoxia and decompression injuries.  Hyperoxia is not without consequence; it reduces cerebral perfusion (CBF).  Characterizing the relationship between FiO2 and CBF is necessary to establish FiO2 levels that do not reduce CBF yet are sufficient to mitigate risk of in-flight physiological stressors.  To achieve that goal, this study’s objective was to determine whether a dose-response relationship exists between FiO2 and CBF and, if so, the FiO2 at which CBF significantly declines.  We found that the neurovascular system appears to respond to increasing FiO2 levels in a dose dependent manner, with significant reductions in CBF with FiO2 exposures ≥ 60%.  

Damato, et al. Aerosp Med Hum Perform (2022).

Funding Source: Department of Defense-US Navy Bureau of Medicine and Surgery, N3239819P0321

Tactical aviation imposes unprecedented physical challenges including repetitive exposure to hypergravity, hyperoxia, increased work of breathing, and profound cognitive workloads.  Each stressor evokes outcomes ranging from musculoskeletal duress and atelectasis to physical and cognitive fatigue, the latter among the foremost threats to aviators.  Whereas sleep loss is traditionally considered the primary cause of fatigue in aviators, converging experimental, observational, and medical studies have identified biochemical mechanisms promoting onset of fatigue.  Those mechanisms, which fundamentally differ from sleep loss, revolve around increased proinflammatory cytokines, produced and released in response to tissue injury, chronic inflammatory disorders, allergens, or physical duress.  This study’s objective was to inform our understanding of potential relationships between serum levels of proinflammatory cytokines and onset of fatigue within a cohort of aviators who experience multiple high-performance sorties on a daily basis.  While fatigue in aviators has been attributed almost solely to sleep loss, nocturnal sorties, or disrupted circadian rhythmicity, our study findings suggest an alternative mechanism that can promote onset of fatigue: increased blood levels of proinflammatory cytokines.

Damato, et al. Front Physiol (2022).

Funding Source: Department of Defense – 711th Human Performance Wing Studies and Analyses Program, F4F4FE0163G001

Disorientation, dizziness, and fatigue can rapidly occur, unprecipitated, during high-performance aviation.  When unnoticed, the outcome can be catastrophic.  Our ongoing studies are defining mechanisms that may contribute to the onset of those symptoms.  The objective of this study was to characterize the neurovascular effects of breathing high concentrations of oxygen, a prerequisite during high-speed and very high altitude aviation, upon overall brain function.  Our study found that high levels of inspired oxygen significantly reduced brain perfusion.  This was accompanied by electroencephalographic (EEG) signatures of enhanced vigilance.  We also found cognitive processes were heightened.  Our data may suggest that the brain's "alerting" mechanisms are activated by a drop in perfusion.

Damato, et al. J Physiol (2020).

Funding Source: Air Force Research Laboratory (AFRL) under the Human Performance Aerospace Physiology Program (contract FA8650-17-F-6822, T.O.  0052)

Newborns exposed to hypoxia, especially in the days following birth, are at risk to become sleepy adolescents who are hyperactive while awake and also have poor working memory.  By characterizing the neurochemical and neuroanatomic structure and function, we found suboptimal performance within the dopaminergic networks.  Those studies formed the scientific structure premise for this project, employing magnetic resonance imaging, high-density electroencephalography, and other techniques to measure brain structure and function in children who were prematurely born and may have been exposed to hypoxia. 

Decker, et al. Sleep Breath (2018).

Funding Source: National Institutes of Health, R21NR017235-01

We describe, in Ethiopia, a third successful pattern of human adaptation to high-altitude hypoxia that contrasts with both the Andean “classic” (erythrocytosis with arterial hypoxemia) and the more recently identified Tibetan (normal venous hemoglobin concentration with arterial hypoxemia) patterns.  A field survey of 236 Ethiopian native residents at 3,530 m (11,650 feet), 14–86 years of age, without evidence of iron deficiency, hemoglobinopathy, or chronic inflammation, found an average hemoglobin concentration of 15.9 and 15.0 g/dl for males and females, respectively, and an average oxygen saturation of hemoglobin of 95.3%.  Thus, Ethiopian highlanders maintain venous hemoglobin concentrations and arterial oxygen saturation within the ranges of sea level populations, despite the unavoidable, universal decrease in the ambient oxygen tension at high altitude.

Beall, et al. Proc Natl Acad Sci USA (2002).

Funding Source: National Geographic Society, Grant 5520-95

Breathing patterns were compared in Tibetan and Andean (Aymara) high‑altitude natives to explain population differences in ventilation at altitude.  Resting ventilation and hypoxic ventilatory response (HVR) were measured in over 800 individuals aged 9–94 years living at 3,800–4,065 m.  Tibetans exhibited ~50% higher resting ventilation and nearly double the HVR compared with Aymara.  These differences were not explained by age or environmental factors and did not increase with lifelong exposure to hypoxia.  Genetic influences were stronger in Tibetans, indicating greater evolutionary potential. Two distinct high‑altitude ventilation phenotypes emerge: Tibetans maintain lifelong high ventilation with moderate HVR, whereas Aymara show slightly elevated ventilation with low HVR.

Beall, et al. Am J Phys Anthropol (1997).

Funding Source: National Science Foundation, Award No. SBR92-21724

Genetic influences on arterial oxygen saturation (SaO₂) were evaluated in 354 healthy, nonpregnant Tibetan high‑altitude residents living at 3,800–4,065 m. Average SaO₂ was 89.4% (range 76–97%).  Family‑based analyses showed that additive genetic effects accounted for 44% of individual variation in SaO₂, with a single major gene explaining 21% of total variation.  Individuals carrying the high‑SaO₂ allele had substantially higher oxygen saturation than those homozygous for the low‑SaO₂ allele.  These findings confirm and extend evidence for a major genetic determinant of oxygen saturation in Tibetans and suggest a selective advantage for higher SaO₂ in chronic high‑altitude hypoxia.

Beall, et al. Hum Biol (1997).

Funding Source: HL43850/HL/NHLBI NIH HHS/United States

Background

Tactical aviation presents multiple physiologic stressors that may compromise a pilot’s ability to effectively accomplish their mission. Among such factors, cognitive fatigue (CF) has been identified as one of the major threats to aviator performance and safety. Although the etiology of CF is multifaceted, prior literature and experimental data suggest a myriad of biochemical mechanisms that promote neuroinflammation and peripheral accumulation of cytokines are all critical elements in the onset of CF. However, the effects of specific nutrients in modulating neuroinflammation and potentially the symptomology of CF is yet to be determined. 

Research Question

Do certain dietary macro/micronutrients exacerbate or attenuate CF?

Methods

Forty-six active duty and reservist T-6A Texan II instructor pilots from Air Force Base #1 (n=24) and Air Force Base #2 (n=22) were studied across a total of twelve days, which included their week-long flight operations. Self-reported 24-hour diet recalls were collected from study participants daily, as were daily multidimensional fatigue inventory (MFI) tests to assess cognitive performance. Additionally, select neuroinflammatory serum analytes were measured at six timepoints over the duration of the study.

Results/Conclusions 

Preliminary data indicates that higher processed food consumption and hence increased saturated fat and trans fat intake is associated with a higher CF level. Further assessment of dietary data will include an index of nutrient quantities that will be compared against MFI results as well as select neuroinflammatory serum analytes to evaluate the presence of a statistical significance association. Additional investigation into possible underlying neural/inflammatory mechanisms will also be conducted to find a plausible biochemical explanation for any uncovered associations. These findings will provide vital insight into the intricate relationship between diet and performance and help inform dietary guidelines for tactical aviators and even other aviators, to reduce CF and optimize mental acuity. 

Conference Poster

Bachra A., Boehringer H., O’Neill S., Damato L., Decker M. Food for better thought: Dietary effects on cognitive fatigue in military pilots. (2025). Midwest/Great Lakes Undergraduate Research Symposium in Neuroscience; Oberlin, OH.

Introduction (Excerpt)

Fatigue outcomes, both cognitive and physical, arise from the unprecedented challenges of tactical and commercial aviation and pose unrelenting threats to pilots, their crew, and passengers. The insidious and progressive onset of fatigue impairs one’s self-awareness, increasing vulnerability towards brain fog, inattention, reduced executive function, situational awareness, and responsiveness. Fatigue’s impact upon a pilot’s performance, as well as overall health, has been well-documented and studied since the mid-1940s, if not earlier. At that time, as today, the challenge has been to develop a definition of aviation-induced fatigue that is synergistic with other definitions used by other occupations and medical disciplines.

Damato, E. G., Boehringer, H. E., Ramakrishnan, N., & Decker, M. J. (2025). Fatigue in aviators: it is not sleepiness. In The Scientific Basis of Fatigue (Chapter 11). Academic Press. https://doi.org/10.1016/B978-0-443-24080-5.00037-0