Ketone Esters for Optimization of Cognitive Performance in Hypoxia

In the setting of altitude-induced hypoxia, cognitive capacity degrades and can compromise both individual and team performance. This degradation is linked to falling brain energy (ATP) levels and an increased reliance on anaerobic energy production from glucose. Ketone bodies are the evolutionary alternative substrate to glucose for brain metabolic requirements; previous studies have shown that the presence of elevated ketone bodies (ketosis) maintains brain ATP levels and reduce cerebral anaerobic glycolysis during hypoxia. Ketosis can be achieved when fasting or following a ketogenic diet; however, these approaches are impractical. Exogenous ketone ester supplementation allows for rapid (< 30 mins) and significant elevation of blood ketone levels without the need to maintain a diet or fast. HVMN, in collaboration with researchers at IHMC, proposes a study to investigate the effects of consuming an FDA-approved ketone ester 'food' on cognitive performance in the setting of hypoxia. For the proposed 4-arm within-subject study, participants will complete a cognitive performance test battery under the conditions of normoxia and then hypoxia following consumption of a ketone ester drink or a placebo drink (N.B for each study drink cognitive performance in both hypoxia and normoxia will be assessed in ONE visit): VISIT A: Arm1: Normoxia + Placebo Arm 2: Hypoxia + Placebo VISIT B: Arm 3: Normoxia + Ketone ester Arm 4: Hypoxia + Ketone ester The investigators hypothesize that ketone ester supplementation will attenuate hypoxia-induced deterioration of operator cognitive performance.

Study drinks will be matched for taste and appearance. Investigator preparing and administering the drink will not carry out the testing.

Flavored sports drink containing deltaG (betahydroxybutyrate monoester) as the sole active ingredient, diluted with water.

Participants will breath through a mask to provide the amount of oxygen typically seen at 16-17,000ft of altitude.

Cognitive performance (visual acuity) will be assessed using the RightEye testing system (https://www.righteye.com).

Measured 3 times (baseline [time = 0 min], during normoxia [time = 30-60 min post study drink 1] and during hypoxia [30-60 min post study drink 2]) in each of the two test visits.

Cognitive performance (contrast sensitivity) will be assessed using the RightEye testing system (https://www.righteye.com).

Measured 3 times (baseline [time = 0 min], during normoxia [time = 30-60 min post study drink 1] and during hypoxia [30-60 min post study drink 2]) in each of the two test visits.

Cognitive performance (choice reaction time) will be assessed using both the RightEye testing system (https://www.righteye.com) and the DANA testing system (http://www.danabrainvital.com).

Measured 3 times (baseline [time = 0 min], during normoxia [time = 30-60 min post study drink 1] and during hypoxia [30-60 min post study drink 2]) in each of the two test visits.

Cognitive performance (eye tracking) will be assessed by looking for smooth pursuit (horizontal and vertical) using the RightEye testing system (https://www.righteye.com).

Measured 3 times (baseline [time = 0 min], during normoxia [time = 30-60 min post study drink 1] and during hypoxia [30-60 min post study drink 2]) in each of the two test visits.

Cognitive performance (eye tracking) will be assessed by looking at saccade speed (horizontal and vertical) using the RightEye testing system (https://www.righteye.com).

Measured 3 times (baseline [time = 0 min], during normoxia [time = 30-60 min post study drink 1] and during hypoxia [30-60 min post study drink 2]) in each of the two test visits.

Cognitive performance (simple reaction time) will be assessed using both the RightEye testing system (https://www.righteye.com) and the DANA testing system (http://www.danabrainvital.com).

Measured 3 times (baseline [time = 0 min], during normoxia [time = 30-60 min post study drink 1] and during hypoxia [30-60 min post study drink 2]) in each of the two test visits.

Measured 3 times (baseline [time = 0 min], after normoxia [60 min post study drink 1] and after hypoxia [60 min post study drink 2]) in each of the two test visits.

Blood ketone levels will be measured in a finger prick blood samples using a clinical grade, handheld glucose/ketone meter (Abott Diabetes Care).

Measured 5 times at regular intervals through each of the two study visits. [time (min) = 0, 30, 75, 105, 150]

Blood glucose levels will be measured in a finger prick blood samples using a clinical grade, handheld glucose/ketone meter (Abott Diabetes Care).

Measured 5 times at regular intervals through each of the two study visits. [time (min) = 0, 30, 75, 105, 150]

Inclusion Criteria: * Pass medical examination on enrollment. Exclusion Criteria: * Active smoker, substance abuse.

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