Ketone Supplement for Sleep Deprivation
(STAK-Sleep Trial)
Recruiting in Palo Alto (17 mi)
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Ohio State University Comprehensive Cancer Center
Must not be taking: Diabetic medications
Disqualifiers: Sleeping disorders, Diabetes, Liver dysfunction, others
No Placebo Group
Approved in 1 Jurisdiction
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. There is some evidence that ketone ester supplements may lessen the adverse effects of sleep restriction. The main purpose of these supplements is to raise your blood concentration of ketones, which are safe, small molecules that appear in the blood during fasting, when following a ketogenic diet, or consuming ketone supplements. The main purpose of this study is to examine if ingesting a ketone ester supplement, twice daily, can improve cognitive and physical performance during short-term sleep restriction.
Do I have to stop taking my current medications for the trial?
The trial protocol does not specify if you need to stop taking your current medications, but it does require you to maintain your medication habits throughout the study.
What evidence supports the effectiveness of the ketone supplement treatment for sleep deprivation?
Research suggests that ketone bodies, like those in ketone supplements, may improve sleep quality by enhancing sleep efficiency and counteracting sleep disruptions, especially after strenuous activities. Additionally, ketone bodies have been linked to better sleep regulation and have shown potential benefits in treating sleep disorders.12345
Is the ketone supplement safe for humans?
How does the ketone supplement treatment for sleep deprivation differ from other treatments?
The ketone supplement treatment for sleep deprivation is unique because it uses ketone bodies, like β-hydroxybutyrate and acetoacetate, to provide an alternative energy source for the brain, potentially improving sleep regulation. Unlike traditional methods that may focus on sleep aids or lifestyle changes, this treatment elevates blood ketone levels through a meal replacement drink, offering a novel approach to managing sleep deprivation.146910
Eligibility Criteria
This trial is for healthy adults aged 18-40, with a BMI of ≤35, who can follow study procedures like fasting and controlled feeding. It's not for those with psychiatric disorders, recent significant weight loss, sleep or gastrointestinal disorders, heavy alcohol use, metabolic diseases (except metformin users), current/recent ketogenic dieters, or pregnant/lactating women.Inclusion Criteria
Participant understands the study procedures and signs forms providing informed consent to participate in the study and authorizes the release of relevant protected health information to the Investigator
Participant has no health conditions that would prevent completion of the study requirements as judged by the Investigator based on health history
Participant is willing and able to comply with all study procedures including fasting (>10 h; water only), no alcohol (>24 h), no exercise (>24 h), no acute illness and controlled feeding before each Test Day, maintain diet, exercise, medication, and supplement habits throughout the study
Exclusion Criteria
Gastrointestinal disorders or food allergies that would interfere with consuming the study supplements
You drink more than 3 drinks a day or 14 drinks a week.
Have any major psychiatric disorders (e.g., schizophrenia, bipolar disorder)
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive either a ketone ester or placebo supplement twice daily during short-term sleep restriction
4 weeks
Multiple visits for assessments and interventions
Washout
A 2-week washout period between crossover interventions
2 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Treatment Details
Interventions
- Ketone Supplement (Ketone Ester Supplement)
Trial OverviewThe study tests if a ketone ester supplement taken twice daily can boost cognitive and physical performance when sleep is restricted. Participants will undergo various assessments including sleep monitoring, heart rate tracking, diet control and performance tests while experiencing short-term sleep deprivation.
Participant Groups
2Treatment groups
Experimental Treatment
Active Control
Group I: Ketone Ester FirstExperimental Treatment13 Interventions
Patients will be randomize to take the ketone ester for the first trial of the intervention, then after a 2 week washout, participants will perform the same intervention but with a placebo
Group II: Placebo FirstActive Control13 Interventions
Patients will be randomize to take the placebo for the first trial of the intervention, then after a 2 week washout, participants will perform the same intervention but with a ketone ester.
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 Comprehensive Cancer CenterLead Sponsor
Ohio State UniversityLead Sponsor
References
Kinetics, safety and tolerability of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in healthy adult subjects. [2022]Induction of mild states of hyperketonemia may improve physical and cognitive performance. In this study, we determined the kinetic parameters, safety and tolerability of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, a ketone monoester administered in the form of a meal replacement drink to healthy human volunteers. Plasma levels of β-hydroxybutyrate and acetoacetate were elevated following administration of a single dose of the ketone monoester, whether at 140, 357, or 714 mg/kg body weight, while the intact ester was not detected. Maximum plasma levels of ketones were attained within 1-2h, reaching 3.30 mM and 1.19 mM for β-hydroxybutyrate and acetoacetate, respectively, at the highest dose tested. The elimination half-life ranged from 0.8-3.1h for β-hydroxybutyrate and 8-14 h for acetoacetate. The ketone monoester was also administered at 140, 357, and 714 mg/kg body weight, three times daily, over 5 days (equivalent to 0.42, 1.07, and 2.14 g/kg/d). The ketone ester was generally well-tolerated, although some gastrointestinal effects were reported, when large volumes of milk-based drink were consumed, at the highest ketone monoester dose. Together, these results suggest ingestion of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate is a safe and simple method to elevate blood ketone levels, compared with the inconvenience of preparing and consuming a ketogenic diet.
Is there a relationship between the ketogenic diet and sleep disorders? [2022]Sleep disorders are very often underestimated and, consequently, not treated with due priority. Common sleep disorders include insomnia disorders, sleep-related breathing disorders, central disorders of hypersomnolence, circadian rhythm sleep-wake disorders, sleep-related movement disorders, parasomnias, and other sleep disorders. The ketogenic diet (KD) is rich in fat, low in carbohydrates (CHO), and adequate in protein. The KD has shown several applications in treating medical conditions, such as epilepsy, neurodegenerative disorders, obesity with its comorbidities, and sleep disorders, with encouraging results. Therefore, the purpose of this review is to address the primary sleep disorders and their respective standard therapeutic approaches, analyse the effect of ketone bodies (KBs) on sleep homeostasis, and the effects of KD on sleep disorders and in particular on obstructive sleep apnoea (OSA) syndrome. The goal is to summarise the evidence existing up to now on the subject, to provide a starting point for further investigations.
Exogenous Ketosis Improves Sleep Efficiency and Counteracts the Decline in REM Sleep after Strenuous Exercise. [2023]Available evidence indicates that ketone bodies may improve sleep quality. Therefore, we determined whether ketone ester (KE) intake could counteract sleep disruptions induced by strenuous exercise.
Ketone body metabolism and sleep homeostasis in mice. [2015]A link has been established between energy metabolism and sleep homeostasis. The ketone bodies acetoacetate and β-hydroxybutyrate, generated from the breakdown of fatty acids, are major metabolic fuels for the brain under conditions of low glucose availability. Ketogenesis is modulated by the activity of peroxisome proliferator-activated receptor alpha (PPARα), and treatment with a PPAR activator has been shown to induce a marked increase in plasma acetoacetate and decreased β-hydroxybutyrate in mice, accompanied by increased slow-wave activity during non-rapid eye movement (NREM) sleep. The present study investigated the role of ketone bodies in sleep regulation. Six-hour sleep deprivation increased plasma ketone bodies and their ratio (acetoacetate/β-hydroxybutyrate) in 10-week-old male mice. Moreover, sleep deprivation increased mRNA expression of ketogenic genes such as PPARα and 3-hydroxy-3-methylglutarate-CoA synthase 2 in the brain and decreased ketolytic enzymes such as succinyl-CoA: 3-oxoacid CoA transferase. In addition, central injection of acetoacetate, but not β-hydroxybutyrate, markedly increased slow-wave activity during NREM sleep and suppressed glutamate release. Central metabolism of ketone bodies, especially acetoacetate, appears to play a role in the regulation of sleep homeostasis.
A ketogenic diet containing medium-chain triglycerides reduces REM sleep duration without significant influence on mouse circadian phenotypes. [2023]Ketogenic diets (KDs) affect the circadian rhythms of behavior and clock gene expression in experimental animals. However, these diets were designed to simulate a fasting state; thus, whether these effects are caused by diet-induced ketogenesis or persistent starvation is difficult to distinguish. The present study aimed to define the effects of a KD containing medium-chain triglycerides (MCT-KD) that increase blood ketone levels without inducing carbohydrate starvation, on circadian rhythms and sleep regulation. Mice were fed with a normal diet (CTRL) or MCT-KD for 2 weeks. Blood β-hydroxybutyrate levels were significantly increased up to 2 mM by the MCT-KD, whereas body weight gain and blood glucose levels were identical between the groups, suggesting that ketosis accumulated without carbohydrate starvation in the MCT-KD mice. Circadian rhythms of wheel-running activity and core body temperature were almost identical, although wheel-running was slightly reduced in the MCT-KD mice. The circadian expression of the core clock genes, Per1, Per2, Bmal1, and Dbp in the hypothalamus, heart, liver, epididymal adipose tissues, and skeletal muscle were almost identical between the CTRL and MCT-KD mice, whereas the amplitude of hepatic Per2 and adipose Per1 expression was increased in MCT-KD mice. The MCT-KD reduced the duration of rapid-eye-movement (REM) sleep without affecting the duration of non-REM sleep and the duration of wakefulness. These findings suggested that the impact of ketone bodies on circadian systems are limited, although they might reduce locomotor activity and REM sleep duration.
Tolerability and Safety of a Novel Ketogenic Ester, Bis-Hexanoyl (R)-1,3-Butanediol: A Randomized Controlled Trial in Healthy Adults. [2021]Nutritional ketosis is a state of mildly elevated blood ketone concentrations resulting from dietary changes (e.g., fasting or reduced carbohydrate intake) or exogenous ketone consumption. In this study, we determined the tolerability and safety of a novel exogenous ketone diester, bis-hexanoyl-(R)-1,3-butanediol (BH-BD), in a 28-day, randomized, double-blind, placebo-controlled, parallel trial (NCT04707989). Healthy adults (n = 59, mean (SD), age: 42.8 (13.4) y, body mass index: 27.8 (3.9) kg/m2) were randomized to consume a beverage containing 12.5 g (Days 0-7) and 25 g (Days 7-28) of BH-BD or a taste-matched placebo daily with breakfast. Tolerability, stimulation, and sedation were assessed daily by standardized questionnaires, and blood and urine samples were collected at Days 0, 7, 14, and 28 for safety assessment. There were no differences in at-home composite systemic and gastrointestinal tolerability scores between BH-BD and placebo at any time in the study, or in acute tolerability measured 1-h post-consumption in-clinic. Weekly at-home composite tolerability scores did not change when BH-BD servings were doubled. At-home scores for stimulation and sedation did not differ between groups. BH-BD significantly increased blood ketone concentrations 1-h post-consumption. No clinically meaningful changes in safety measures including vital signs and clinical laboratory measurements were detected within or between groups. These results support the overall tolerability and safety of consumption of up to 25 g/day BH-BD.
Safety and tolerability of sustained exogenous ketosis using ketone monoester drinks for 28 days in healthy adults. [2020]Throughout history, the only way humans could raise their blood ketone levels was by several days of fasting or by following a strict low-carb, high-fat diet. A recently developed, dietary source of ketones, a ketone monoester, elevates d-β-hydroxybutyrate (βHB) to similar concentrations within minutes, with βHB remaining raised for several hours. To date, the longest human safety study of the exogenous ketone ester was for 5 days, but longer consumption times may be desired. Here we report results for 24 healthy adults, aged 18-70 years, who drank 25 ml (26.8 g) of the ketone monoester, (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, three times a day for 28 days (a total of 2.1 L). Anthropomorphic measurements, plus fasting blood and urine analyses were made weekly. It was found that elevating blood βHB concentrations from 0.1 to 4.1 (±1.1) mM three times a day for 28 days had no effect on body weights or composition, fasting blood glucose, cholesterol, triglyceride or electrolyte concentrations, nor blood gases or kidney function, which were invariably normal. Mild nausea was reported following 6 of the 2,016 drinks consumed. We conclude that sustained exogenous ketosis using a ketone monoester is safe and well-tolerated by healthy adults.
(R)-3-oxobutyl 3-hydroxybutanoate (OBHB) induces hyperketonemiain Alzheimer's disease. [2020]The present study demonstrates the effect of (R)-3-oxobutyl 3-hydroxybutanoate (OBHB) on hyperketonemia in 2 patients with Alzheimer's disease dementia who were performed a mini-mental state examination score of above 11 and 10. The patients were treated with OBHB for 24 months and received usual diet. The patients were administered 15 g of OBHB three times per day for two days. The dosage of OBHB was increased to 30 g three times daily from the day 4. OBHB was always taken after adding with soda-flavoured syrups in order to mask the bitter taste. The measurement of plasma β-hydroxybutyrate (βHB) levels after every week was performed to determine OBHB plasma βHB dose-response relationships. Precision Xtra Glucose and Ketone Monitoring System (Abbott Diabetes Care, Inc., Alameda, CA, USA) was used to measure βHB levels in the blood samples. We did not observe any adverse effects of OBHB in any of the patients and it was well tolerated throughout the 24 months treatment period. Both of the patients showed marked improvement in mood, behaviour, self-care, cognitive and daily activity performance. The results revealed a marked improvement in conversation and interaction after administration of OBHB doses. The biochemical investigation of the blood samples before, during OBHB treatment and after 24 months of the treatment revealed only minor changes in the plasma lipids. There was a decrease in cholesterol level from 251 to 158 and 247 to 152 mg/dL in the two patients respectively after 24 months of the treatment. Similarly the level of high-density lipoprotein cholesterol was found to decrease from 157 to 79 and 149 to 76 mg/dL, respectively in two patients. Thus OBHB can be a promising agent in the treatment of hyperketonemia and can be taken as an oral supplement without changing the habitual diet.
The effect of a 2 week ketogenic diet, versus a carbohydrate-based diet, on cognitive performance, mood and subjective sleepiness during 36 h of extended wakefulness in military personnel: An exploratory study. [2023]Extended wakefulness, or sleep deprivation, impairs cognitive performance and brain glucose metabolism. A ketogenic diet (KD) provides an alternative fuel source, ketone bodies, that could elicit a metabolic benefit during sleep deprivation. A randomised, cross-over trial was conducted with seven male military personnel. Participants ingested an iso-energetic ketogenic diet or carbohydrate-based diet for 14 days, immediately followed by 36 h of extended wakefulness and separated by a 12 day washout. Cognitive performance, mood, subjective sleepiness, capillary blood glucose, and D-β-hydroxybutyrate concentrations were measured every 2 h during extended wakefulness. Linear mixed models were used to analyse data. D-β-hydroxybutyrate was higher (p
A Novel Powder Formulation of the Ketone Ester, Bis Hexanoyl (R)-1,3-Butanediol, Rapidly Increases Circulating ß-Hydroxybutyrate Concentrations in Healthy Adults. [2023]Objective: Growing interest in the metabolic state of ketosis has driven development of exogenous ketone products to induce ketosis without dietary changes. Bis hexanoyl (R)-1,3-butanediol (BH-BD) is a novel ketone ester which, when consumed, increases blood beta-hydroxybutyrate (BHB) concentrations. BH-BD is formulated as a powder or ready-to-drink (RTD) beverage; the relative efficacy of these formulations is unknown, but hypothesized to be equivalent.Methods: This randomized, observer-blinded, controlled, crossover decentralized study in healthy adults (n = 15, mean age = 33.7 years, mean BMI = 23.6 kg/m2) aimed to elucidate blood BHB and glucose concentrations before and 15, 30, 45, 60, 90 and 120 minutes following two serving sizes of reconstituted BH-BD powder (POW 25 g, POW 12.5 g), compared to a RTD BH-BD beverage (RTD 12.5 g), and a non-ketogenic control, all taken with a standard meal.Results: All BH-BD products were well tolerated and increased BHB, inducing nutritional ketosis (BHB ≥0.5 mM) after ∼15 minutes, relative to the control. BHB remained elevated 2 h post-consumption. The control did not increase BHB. Ketosis was dose responsive; peak BHB concentration and area under the curve (AUC) were two-fold greater with POW 25 g compared to POW 12.5 g and RTD 12.5 g. There were no differences in peak BHB and AUC between matched powder and RTD formulas. Blood glucose increased in all conditions following the meal but there were neither significant differences in lowest observed concentrations, nor consistent differences at each time point between conditions. These results demonstrate that both powdered and RTD BH-BD formulations similarly induce ketosis with no differences in glucose concentrations in healthy adults.