Ketone Conferred Resiliency Against Sleep Restriction With Nutritional Intervention.

Sleep deprivation is a major problem in military populations. Some major consequences of sleep loss are inability to concentrate, poor work efficiency, and increase in errors during daily tasks. Ketogenic supplementation is speculated to alleviate some sleep deprivation issues via action of ketones. Ketones are small molecules that appear in the blood when following a ketogenic diet or consuming ketone supplements. The goal of this project is to find out if diet and/or ketones can improve sleep deprivation detriments over 5 days of sleep restriction (-50% from habitual sleep).

We will conduct a double-blind, randomized and balanced 3-arm intervention (n = 20 x 3 conditions). Diet randomization will be determined by using an online randomization tool (www.randomizer.org). Participants (total n = 60-80) will be familiarized with all the physical performance tests to minimize learning effects and undergo baseline assessments. On the morning of Day 1 subjects will undergo Pre-Testing inclusive of a blood draw, physical, and cognitive performance. For that night, and the next 4 nights, all subjects will restrict their sleep by 50%. After Day 5, a six-week feeding period will begin according to the participant randomization: ketogenic diet (KD), mixed diet + placebo (MD+PL) or mixed diet + ketone ester (MD+KE). After a six-week feeding period, during which time participants return to their normal sleep and exercise habits, they will replicate the exact same 5-day sleep deprivation protocol before finishing all the study duties.

Test Day 1 \& 5: Participants will arrive at the testing lab between 6:00-9:00h, hydrated and after an overnight fast (\<8h). Hydration/Surveys: Hydration will be measured non-invasively in a fasted urine sample via light refractometry. Well-being will be assessed using questionnaires. Blood Draws: After 10 minutes of rest, a trained phlebotomist will perform an intravenous blood draw from the antecubital fossa using a 21G butterfly needle. Total blood collected will be limited to two test tubes (total volume 2 x 10mL): EDTA plasma and serum. Supplement Ingestion: The first supplement dose (either KE or PL) will be consumed before commencing the cognitive testing battery. DXA: One, 7-minute whole-body scan will be conducted to assess lean-body mass and fat mass changes pre- to post-diet. This will occur on day 1 testing only during the first and second sleep deprivation protocol. Cognitive Tests: A series of computer and iPad-based cognitive tests will be administered to each participant to measure their attention, information processing, memory, function, inhibition, and social and emotional domains. VirTra: Participants will be tested on shooting competency using compressed gas weapons. Measures of reaction time, accuracy, precision, and spread will be recorded by a trained team member present in the room. Power/Strength: Whole body power and strength will be assessed using a 3 (trial) x 2 (L/R hand) manual handgrip testing, 3 (consecutive jump) x 3 (set) countermovement jump (CMJ) while on an electronic force plate, and lastly, a maximal isometric mid-thigh pull, also on the force plate. Participants will undergo testing in this order to minimize total body fatigue. All exercises will be demonstrated by a team physiologist. Response time: Upper body and lower body reaction time will be measured using the Quick Board. The Quick Board system is comprised of an iPad Quick Board application and a footpad with 5 sensors placed equidistant from each other, with two at the front of the footpad, two at the back of the footpad, and one in the middle of the footpad. Upper and lower body reaction time will be measured using hands and legs, respectively. After Day 1, participants will be instructed to restrict their sleep to 50% of their habitual sleeping duration. After testing on Day 5 (i.e. after 4 nights of consecutive sleep restriction) the participants will start the diet that they were assigned to and can resume regular sleeping habits ; after six weeks, they will return to the lab to begin their second sleep deprivation battery. During the study, participants will record daily morning fasting capillary ketone and glucose. Additionally, the Polar Watch/Chest Strap will measure activity and heart rate, and the Oura ring will measure sleep quality and architecture.

Test Days 2/3/4: Exercise habits will be assessed using a previously validated survey. We will then provide a structured workout program to follow on Days 2, 3, and 4. The program emphasizes strength, power, and hypertrophy. Using the provided Excel sheet, all the exercise repetitions and sets will be recorded during each training day. The Excel sheet will be returned to the study team on Day 5.

Six-Week Feeding Intervention: All food items will be provided to the participants. Food will arrive in cold, vacuum sealed containers that are microwave-safe and ready-to-eat. Each item is labeled in accordance with USDA rules and regulations. Participants will be responsible for picking food up from the testing center on a weekly basis. Depending on calorie needs, some participants may receive more food than just pre-packaged breakfast, lunch, and dinner to cover their total daily energy requirements.

Eligibility Criteria:
Inclusion Criteria:

* Healthy, 18-40 years old.
* BMI: 20-35 kg/m2
* Sleep at least 7h per night.
* Willing to participate in \~9-weeks of testing and provided food.
* Willing to adhere to all study procedures.

Exclusion Criteria:

* \<18 or \>40 years of age
* \>35 body mass index (BMI).
* Diagnosed sleeping disorders (i.e., sleep apnea, insomnia).
* Gastrointestinal disorders or food allergies that would interfere with consuming the study supplements.
* Drink alcohol in excess of 3 drinks/day or 14 drinks/week
* Have any conditions or contraindications to blood draws.
* Have been diagnosed with diabetes, liver, kidney, or other metabolic or endocrine dysfunction, or use diabetic medications other than metformin
* Currently consume a low carbohydrate or ketogenic diet or have done so in the last 3 months
* Have experienced weight loss of \>10% of your body weight within the last 6 months
* Are pregnant, lactating, or planning on becoming pregnant during the study
* Have any major psychiatric disorders (e.g., schizophrenia, bipolar disorder)