Study for U.S. Air Force Research Lab tracks impact of ketones on pilot ventilation

Military aviators breathe rarefied air — figuratively and literally.

They operate elite aircraft at altitude in stressful conditions with protections in place to ensure that the atmosphere they breathe in flight helps ensure their physical and cognitive performance doesn’t suffer in the extreme conditions they are asked to navigate.

Finding ways to ensure proper ventilation in pilots is what underlies an ongoing research project at the Florida Institute for Human and Machine Cognition sponsored by the U.S. Air Force Research Laboratory. It aims to assess the effects of exogenous ketones on operator ventilation.

“When you’re dealing with these oxygen delivery systems in the aircraft, typically the failures are intermittent,” says Research Scientist Dr. David Morris, part of the study team led by Senior Research Scientist Dr. Jeff Phillips. “It’s not total failure of the system, but because of the way they’re designed, you can get reductions in oxygen flow from time to time for periods of time.”

For nearly two decades, unexplained physiological episodes (UPEs) have been a challenge to aviators. Studies have identified a few factors that may play a role in UPEs:

  • Hypobaria (low ambient pressures)
  • Breathing hyperoxic (high oxygen level) gas
  • Obstructive breathing resistance
  • Hypocapnia (low blood carbon dioxide levels) associated with hypobaria, hyperoxia, and breathing resistance.

Military aviators wear oxygen masks that allow them to breathe hyperoxic air, a standard operating strategy that provides adequate oxygen in flight and protects against decompression sickness in case of sudden depressurization of the aircraft.

Breathing this hyperoxic air causes hyperventilation, breathing out more carbon dioxide than the body produces. Since carbon dioxide helps regulate blood flow to the brain, a deficit of it in the bloodstream can reduce blood flow to the brain. It also raises your blood’s pH which makes the affinity of oxygen to hemoglobin so high that the oxygen doesn’t get released from the red blood cells to get to the actual tissue to support metabolic processes. Paradoxically, breathing hyperoxic gas may result in reduced oxygen delivery to the brain and lead to a UPE.

The hypothesis for the ongoing IHMC study is that drinking exogenous ketones will lower the body’s pH and increase metabolic production of carbon dioxide when compared to a placebo and mitigate the potential impacts on aviators’ physiology.

The early results are promising.

“We believe that this could be a way to help make our aviators safer and offer them some metabolic protection, if you will, from the effects of hypocapnia at altitude,” Morris says. “By helping maintain carbon dioxide levels in the blood, we hope that we can offer a buffer for aviators to help protect them against possible UPEs.”

Morris says that participants on the ketones were able to maintain more normal breathing. On the placebo, participants’ breathing just stayed flat even after they transition from hyperoxia to hypoxia and their blood oxygen levels dropped.

“On the ketones, not only did they maintain higher ventilation volumes during hypoxia, that hypoxic ventilatory response happened almost immediately. On the carbohydrates, it was delayed,” Morris says.

The findings could be applicable to other warfighters who work at altitude as well as have impacts mitigating the risk of frostbite and freeze-related injuries.

“From a physical standpoint, if you have more oxygen in the blood, typically you’re going to maintain better blood flow to your fingers and toes, especially in cold environments” Morris says.

Some evidence also suggests that exogenous ketones may help to alleviate a condition known as hypoxic pulmonary vasoconstriction.

In this condition, the blood vessels in the lungs constrict in response to hypoxia which causes the blood pressure in the lungs to rise. This causes a couple of problems. In the short term, fluid is forced from the bloodstream and into the lungs, causing a potentially deadly condition known as high-altitude pulmonary edema.

If the person’s hypoxia is caused by a chronic lung disease such as chronic obstructive pulmonary disease, the pulmonary hypertension can become chronic and lead to heart failure.

“We’re currently looking for funding to pursue this line of research,” Phillips says. “We think the possibilities are exciting.”

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