Effects of Pre-dive Ketone Food Products on Latency to CNS Oxygen Toxicity (Aim 2)

Overview

The purpose of this study is to understand how ketogenic food products affect oxygen toxicity in undersea divers. Oxygen toxicity affecting the central nervous system, mainly the brain, is a result of breathing higher than normal oxygen levels at elevated pressures as can be seen in SCUBA diving or inside a hyperbaric (pressure) chamber. This is a condition that may cause a wide variety of symptoms such as: vision disturbances, ear-ringing, nausea, twitching, irritability, dizziness, and potentially loss of consciousness or seizure. Because nutritional ketosis has been used to reduce or eliminate seizures in humans, it may be beneficial to reduce oxygen toxicity as well. The investigators hope this study will provide a help to develop practical and useful methods for improving the safety of undersea Navy divers, warfighters and submariners.

Central nervous system (CNS) oxygen toxicity continues to be a risk for military divers and constrains their operations. Manifestations of this condition range from nausea, twitching, and tinnitus to seizures and unresponsiveness, and the latter may lead to death by drowning. The NAVY has a need for better methods to prevent or delay the onset of CNS oxygen toxicity (CNSOT) and to safely expand the scope of diving operations. It is the broad objective of this study to generate information that will enhance warfighter safety and performance in relevant NAVY operations by reducing the risk of CNS oxygen toxicity. It is known that nutritional ketosis through a diet with a high fat-to-carbohydrate ratio (ketogenic diet) can reduce the frequency and severity of epileptic seizures in humans, and a recent animal study has shown that dietary ketosis also delays the onset of CNSOT. In recent years, ketone ester food products ketone esters have been made commercially available which may elevate circulating ketone levels. The investigators aim to investigate whether ketosis from commercially available ketogenic food products prior to a dive will delay the onset of CNSOT. The first aim of this study will be to determine the effect of ketone food product ingestion on serum ketone levels, and document any relevant side effects. Post-ingestion ketone levels will be trended for 3 different ketone food product regimens in 15 total subjects. Data will be used to select the optimal ketone food product strategy to investigate in the second aim. This second aim will be to evaluate the primary hypothesis, that pre-dive ketone food products will prolong latency to CNSOT. To assess this, 20 subjects will be studied in a randomized, controlled, double-blind, crossover methodology. After consuming either the ketone food product or placebo, each subject will complete an immersed, head out hyperbaric oxygen exposure while exercising on an underwater cycle ergometer at 2.06 ATA (35 fsw) until oxygen toxicity symptoms develop or the maximum time limit of 120 minutes is reached. The experiment will be repeated on a different day by each subject after consuming the opposite (ketone food products or placebo). Primary outcome will be time to manifestation of CNSOT. Physiologic monitoring throughout the study will provide secondary endpoints such as cognitive performance, sympathetic nervous system stimulation via electrodermal activity, electroencephalography, cardiorespiratory measures and end-tidal CO2/O2/N2; all adding to our understanding of CNSOT physiology which may guide future mitigation and monitoring strategies.