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~21 spots leftby Jun 2026

Ketone Ester + Nutritional Intervention for Sleep Deprivation

Recruiting in Palo Alto (17 mi)

Overseen byJeff S Volek, PhD

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Ohio State University

Must not be taking: Diabetic medications

Disqualifiers: Sleeping disorders, Diabetes, Liver, others

Trial Summary

What is the purpose of this trial?

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).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are using diabetic medications other than metformin, you may not be eligible to participate.

What data supports the effectiveness of the treatment Ketone Ester + Nutritional Intervention for Sleep Deprivation?

Research suggests that ketone bodies, which can be increased through ketone ester intake, may improve sleep quality and counteract sleep disruptions, especially after strenuous exercise. This indicates potential benefits for sleep deprivation.¹ ² ³ ⁴ ⁵

Is the Ketone Ester + Nutritional Intervention safe for humans?

Research shows that ketone esters, like bis-hexanoyl-(R)-1,3-butanediol and (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, are generally safe and well-tolerated in healthy adults, with no significant changes in vital signs or lab measurements. Some mild gastrointestinal effects were reported at high doses, but overall, these supplements are considered safe for increasing blood ketone levels.² ³ ⁴ ⁵ ⁶

How does the Ketone Ester + Nutritional Intervention treatment for sleep deprivation differ from other treatments?

This treatment is unique because it uses ketone esters to quickly induce a state of ketosis, which may improve sleep quality by counteracting disruptions caused by factors like strenuous exercise. Unlike traditional methods that require dietary changes, this approach allows for rapid ketosis through oral supplementation, potentially offering a novel way to enhance sleep without significant lifestyle alterations.¹ ² ³ ⁴ ⁷

Research Team

Jeff S Volek, PhD

Principal Investigator

Ohio State University

Eligibility Criteria

This trial is for healthy adults aged 18-40 with a BMI of 20-35, who sleep at least 7 hours nightly and are willing to undergo about 9 weeks of testing with provided food. Excluded are those with sleeping or major psychiatric disorders, certain dietary habits or conditions, recent significant weight loss, pregnancy, excessive alcohol consumption, or metabolic/endocrine dysfunctions.

Inclusion Criteria

You need to sleep for at least 7 hours each night.

Willing to adhere to all study procedures

I am healthy and between 18 to 40 years old.

See 2 more

Exclusion Criteria

Have any conditions or contraindications to blood draws

You have a BMI over 35.

Gastrointestinal disorders or food allergies that would interfere with consuming the study supplements

See 8 more

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo baseline assessments including familiarization with physical performance tests and baseline cognitive and physical testing

1 day

1 visit (in-person)

Sleep Restriction and Testing

Participants undergo a 5-day sleep restriction protocol with cognitive and physical performance testing

5 days

5 visits (in-person)

Feeding Intervention

Participants follow a 6-week diet intervention with either ketogenic diet, Mediterranean diet with ketone ester, or Mediterranean diet with placebo

6 weeks

Weekly food pickup

Second Sleep Restriction and Testing

Participants replicate the 5-day sleep restriction protocol with cognitive and physical performance testing after the feeding intervention

5 days

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the intervention

4 weeks

Treatment Details

Interventions

Ketogenic Intervention (Other)
Ketone Ester (Dietary Supplement)
Mediterranean Intervention (Other)
Placebo (Dietary Supplement)

Trial OverviewThe study investigates if diets (Mediterranean or Ketogenic) or ketone supplements can mitigate the negative effects of sleep deprivation over five days where participants get half their usual amount of sleep. Participants will receive either a ketone ester supplement, Mediterranean diet intervention, ketogenic diet intervention, or placebo.

Participant Groups

3Treatment groups

Experimental Treatment

Active Control

Placebo Group

Group I: Ketogenic Diet ArmExperimental Treatment1 Intervention

The goal of the KD is to have participants achieve consistent blood BHB ≥0.5 mM; preferably in the range of \>1 to 3 mM. We will measure ketones daily via finger stick to provide individual feedback and provide a quantitative measure of compliance. The KD will consist of approximately 50 g carbohydrate and 1.5 g/kg reference weight protein. These may be adjusted based on daily BHB readings. Fat will comprise the remaining calories with an emphasis on monounsaturated and saturated sources from whole foods. A wide range of foods will be incorporated including non-starchy vegetables, fruits (berries, olives, tomatoes, lemons/limes), meats (beef, chicken, pork, fish, lamb), nuts and seeds, oils (olive, canola, coconut), cheese, butter, cream, eggs, and fatty fish (salmon, sardines). Nutritional ketosis is associated with natriuresis that will lead to sodium and fluid loss if the extra sodium excreted is not compensated, thus slightly higher sodium and potassium intakes will be required.

Group II: Mediterranean Diet + Ketone EsterActive Control2 Interventions

The MD+KE arm will consume the exact same diet as the MD+PL group with the exception they will consume two daily doses of KE instead of the placebo.

Group III: Mediterranean Diet + PlaceboPlacebo Group2 Interventions

The MD+PL arm will be modeled after a Mediterranean style eating pattern. It will contain the same amount of protein as the KD, but with slight variations in protein sources, including limiting red meat to 1x/wk. The diet will provide unprocessed, higher-fiber foods with emphasis on vegetables, fruits, nuts and seeds, legumes, tubers, whole grains, and fish and seafood. Poultry, eggs, cheese, and yogurt will be included in moderate amounts. Use of olive oil and other monounsaturated fat sources (e.g., avocados and olives) will be encouraged while keeping added sugars to a minimum and avoiding highly processed foods (refined grains, fruit juice, processed meats). Saturated fat will be \<10% of energy. We will include adequate omega-3 fats (e.g., salmon). No alcohol will be included in both diets, but we will track consumption. This group will also consume two daily doses of placebo.

Find a Clinic Near You

Research Locations NearbySelect from list below to view details:

The Ohio State UniversityColumbus, OH

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Who Is Running the Clinical Trial?

Ohio State University

Lead Sponsor

Trials

891

Patients Recruited

2,659,000+

Findings from Research

A one-day ketogenic diet significantly increased total energy expenditure by about 110 calories compared to an isocaloric control diet, suggesting it may help with energy balance.

Supplementation with exogenous ketone salts did not enhance energy expenditure or appetite regulation compared to the isocaloric control diet, indicating that they may not provide additional benefits in energy balance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of one-day fasting, ketogenic diet or exogenous ketones on control of energy balance in healthy participants.Hägele, FA., Dörner, R., Koop, J., et al.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exogenous Ketosis Improves Sleep Efficiency and Counteracts the Decline in REM Sleep after Strenuous Exercise.Robberechts, R., Albouy, G., Hespel, P., et al.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and Safety of a Novel Ketogenic Ester, Bis-Hexanoyl (R)-1,3-Butanediol: A Randomized Controlled Trial in Healthy Adults.Chen, O., Blonquist, TM., Mah, E., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of exogenous ketone supplementation on blood ketone, glucose, triglyceride, and lipoprotein levels in Sprague-Dawley rats.Kesl, SL., Poff, AM., Ward, NP., et al.[2020]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketogenic diets and Ketone suplementation: A strategy for therapeutic intervention.Saris, CGJ., Timmers, S.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kinetics, safety and tolerability of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in healthy adult subjects.Clarke, K., Tchabanenko, K., Pawlosky, R., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ingested Ketone Ester Leads to a Rapid Rise of Acetyl-CoA and Competes with Glucose Metabolism in the Brain of Non-Fasted Mice.Suissa, L., Kotchetkov, P., Guigonis, JM., et al.[2021]