Ketone Supplementation for Enhancing Ketosis

(STAK: OK'd Trial)

Overseen by Jeff S Volek, PhD

Age: 18 - 65

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Ohio State University

Disqualifiers: Hypertension, Diabetes, Neurologic, Psychiatric, others

Trial Summary

What is the purpose of this trial?

This trial tests different types of ketone supplements and a precursor to see how they affect metabolism. The study involves participants who meet specific health and dietary criteria. These supplements increase ketone levels in the blood, offering an alternative energy source to glucose.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires that you maintain your medication habits throughout the study. If you have unstable use of a medication that might affect the trial outcomes, you may be excluded.

What data supports the effectiveness of the treatment Ketone Supplementation for Enhancing Ketosis?

Research shows that ketone esters, like the ones in this treatment, can increase blood ketone levels, which may help reduce seizures in epilepsy and decrease body weight and liver fat in mice. Additionally, ketone drinks have been shown to effectively induce ketosis in humans, which is linked to various health benefits. ^{1 2 3 4 5}

Is ketone supplementation safe for humans?

Research shows that ketone supplementation, such as (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, is generally safe and well-tolerated in humans, although some people may experience mild stomach issues when consuming large amounts. ^{1 2 3 6 7}

How does the ketone supplementation treatment differ from other treatments for enhancing ketosis?

This treatment is unique because it uses ketone esters and diesters to induce ketosis without requiring dietary changes, unlike traditional methods that rely on a high-fat, low-carbohydrate diet. It elevates blood ketone levels quickly and is generally well-tolerated, offering a practical alternative to achieve ketosis. ^{4 5 6 8 9}

Research Team

Jeff S Volek, PhD

Principal Investigator

Ohio State University

Eligibility Criteria

This trial is for healthy males aged 20-30, with a BMI of 18-29 kg/m^2 who don't smoke or use cannabis, haven't used ketone supplements or followed a low-carb diet recently, and aren't taking part in other studies. They must be able to fast and avoid alcohol before test days.

Inclusion Criteria

I understand the study and have signed the consent forms.

I am male.

Your body mass index (BMI) is between 18 and 29.

Exclusion Criteria

Participant has a known allergy, intolerance, or sensitivity to any of the ingredients in the study beverages

Participant has had a blood draw or donation in the last 8 weeks

I have a serious stomach or intestine condition that could affect the study.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants consume different ketone esters and precursors, with repeated blood sampling and metabolic measurements

6 weeks

Multiple visits (in-person) every 2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• AcAc Diester (Ketone Supplement)
• BDO (Dietary Supplement)
• BHB Monoester (Ketone Supplement)
• C6 Diester (Ketone Supplement)

Trial Overview The study compares the effects of different Ketone Ester (KE) compounds and Butanediol (BDO), which are believed to affect metabolism differently. It's a full crossover study where participants will try all KE types at two serving sizes to see how they impact ketones, glucose, and acid-base balance.

Participant Groups

Group I: C8 Ketone Di-ester 360mg/kg Experimental Treatment 7 Interventions

Group II: C8 Ketone Di-ester 180mg/kg Experimental Treatment 7 Interventions

Group III: BHB mono-ester 360mg/kg Experimental Treatment 7 Interventions

Group IV: BHB Mono-ester 180mg/kg Experimental Treatment 7 Interventions

Group V: AcAc Di-ester 360mg/kg Experimental Treatment 7 Interventions

Group VI: AcAc Di-ester 180mg/kg Experimental Treatment 7 Interventions

Group VII: (R)-1,3 butanediol 360mg/kg Experimental Treatment 7 Interventions

Group VIII: (R)-1,3 butanediol 180mg/kg Experimental Treatment 7 Interventions

Group IX: Control Placebo Group 8 Interventions

Who Is Running the Clinical Trial?

Ohio State University

Lead Sponsor

Trials

891

Recruited

2,659,000+

Dr. John J. Warner

Ohio State University

Chief Executive Officer since 2023

MD, MBA

Dr. Peter Mohler

Ohio State University

Chief Medical Officer since 2023

PhD in Molecular Biology

Ohio State University Comprehensive Cancer Center

Lead Sponsor

Trials

350

Recruited

295,000+

Dr. David Cohn

Ohio State University Comprehensive Cancer Center

Interim Chief Executive Officer since 2022

MD, MBA

Dr. David Cohn

Ohio State University Comprehensive Cancer Center

Chief Medical Officer since 2018

MD

Findings from Research

A synthetic ketone ester (BD-AcAc2) was found to effectively raise the seizure threshold in a rat model, indicating its potential as an anti-seizure treatment by elevating blood ketone levels.

The study showed that BD-AcAc2 increased blood β-hydroxybutyrate levels significantly compared to the control, suggesting that this compound could serve as a pharmacological alternative to the ketogenic diet for managing epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anticonvulsant properties of an oral ketone ester in a pentylenetetrazole-model of seizure. Viggiano, A., Pilla, R., Arnold, P., et al.[2015]

In a study involving 16 male mice on a high-fat, high-sugar diet, the addition of the ketone diester BD-AcAc2 significantly reduced weight gain (only 13% increase compared to 56% in the control group) and markers of liver disease, indicating its potential efficacy in managing obesity-related liver issues.

The KE group showed significantly lower levels of hepatic inflammation and fibrosis compared to the control group, suggesting that BD-AcAc2 can effectively mitigate liver damage even when carbohydrate intake is not restricted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary ketone ester attenuates the accretion of adiposity and liver steatosis in mice fed a high-fat, high-sugar diet. Rushing, KA., Bolyard, ML., Kelty, T., et al.[2023]

A diet with 30% energy from the ketone ester BD-AcAc2 led to a significant 12% reduction in energy intake compared to the control group, resulting in lower body weight and fat mass in mice.

Diets with 20% and 25% energy from BD-AcAc2 also reduced body weight and fat mass without affecting energy intake or expenditure, suggesting that these concentrations can effectively promote weight loss independently of calorie consumption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concentration-Dependent Effects of a Dietary Ketone Ester on Components of Energy Balance in Mice. Deemer, SE., Davis, RAH., Gower, BA., et al.[2022]

Exogenous ketone drinks, such as ketone esters and ketone salts, effectively raise blood D-β-hydroxybutyrate (D-βHB) levels, with significant increases observed in a study of 15 participants, indicating a practical alternative to traditional ketogenic diets.

Both types of ketone drinks lowered blood glucose and triglyceride levels without causing adverse effects on blood electrolytes, suggesting they are safe and beneficial for metabolic health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

On the Metabolism of Exogenous Ketones in Humans. Stubbs, BJ., Cox, PJ., Evans, RD., et al.[2022]

A novel ketone di-ester, bis hexanoyl (R)-1,3-butanediol (BH-BD), effectively raises blood levels of beta-hydroxybutyrate (BHB) to 0.8-1.7 mM in healthy adults, indicating successful induction of ketosis without dietary changes.

The study showed that higher doses of BH-BD (25g) resulted in greater increases in BHB levels compared to lower doses (12.5g), while also decreasing plasma glucose and free fatty acids, suggesting potential metabolic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bis Hexanoyl (R)-1,3-Butanediol, a Novel Ketogenic Ester, Acutely Increases Circulating r- and s-ß-Hydroxybutyrate Concentrations in Healthy Adults. Crabtree, CD., Blade, T., Hyde, PN., et al.[2023]

Oral administration of the ketone ester BD-AcAc(2) significantly delayed the onset of CNS oxygen toxicity seizures in rats by increasing levels of acetoacetate and acetone, demonstrating a potential new strategy for seizure mitigation.

In contrast, another compound, 1,3-butanediol, induced ketosis but did not delay seizures, highlighting the specific efficacy of BD-AcAc(2) in enhancing seizure latency through its unique metabolic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic ketosis with ketone ester delays central nervous system oxygen toxicity seizures in rats. D'Agostino, DP., Pilla, R., Held, HE., et al.[2020]

In a 28-day study involving 59 healthy adults, the novel exogenous ketone diester bis-hexanoyl-(R)-1,3-butanediol (BH-BD) was found to be well-tolerated and safe, with no significant differences in tolerability scores compared to a placebo.

BH-BD effectively increased blood ketone levels one hour after consumption, indicating its potential for promoting nutritional ketosis without adverse effects on vital signs or laboratory measures.

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]

In a study with conscious dogs, the ingestion of R,S-1,3-butanediol diacetoacetate induced ketosis, but the achieved level (0.8 mM) was lower than the levels (1-3 mM) seen in children on a ketogenic diet for epilepsy.

The study suggests that while the ketosis level in dogs was lower, humans might experience higher ketone body concentrations from the same doses of the ester, potentially making it a viable option for managing seizures in children with intractable epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dog model of therapeutic ketosis induced by oral administration of R,S-1,3-butanediol diacetoacetate. Puchowicz, MA., Smith, CL., Bomont, C., et al.[2022]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Anticonvulsant properties of an oral ketone ester in a pentylenetetrazole-model of seizure. [2015]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Dietary ketone ester attenuates the accretion of adiposity and liver steatosis in mice fed a high-fat, high-sugar diet. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Concentration-Dependent Effects of a Dietary Ketone Ester on Components of Energy Balance in Mice. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

On the Metabolism of Exogenous Ketones in Humans. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Bis Hexanoyl (R)-1,3-Butanediol, a Novel Ketogenic Ester, Acutely Increases Circulating r- and s-ß-Hydroxybutyrate Concentrations in Healthy Adults. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Kinetics, safety and tolerability of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in healthy adult subjects. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Therapeutic ketosis with ketone ester delays central nervous system oxygen toxicity seizures in rats. [2020]

8. Switzerland 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. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Dog model of therapeutic ketosis induced by oral administration of R,S-1,3-butanediol diacetoacetate. [2022]