Ketone Supplements for Ketosis

(STAK-VKM Trial)

Recruiting at1 trial location

Overseen by Jeff Volek, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Ohio State University

Disqualifiers: Diabetes, Hypertension, Psychiatric, GI, others

No Placebo Group

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial studies how different ages and overall health affect the body's response to a special drink. Participants will consume the drink, and researchers will measure how their bodies process it by checking blood and urine levels.

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 your medication use is unstable and might affect the trial outcomes, you may be excluded from participating.

What data supports the effectiveness of the treatment Ketone Supplements for Ketosis?

Research shows that ketone supplements, like the ones used in the trial, can safely increase blood ketone levels, which is a state known as ketosis. This state has been associated with potential benefits for physical and cognitive performance, making ketone supplements a practical way to achieve ketosis without dietary changes. ^{1 2 3 4 5}

Is it safe for humans to consume ketone supplements?

Research shows that ketone supplements, like ketone esters and monoesters, are generally safe and well-tolerated in healthy adults. Some mild gastrointestinal effects, like nausea, may occur, especially at higher doses, but no significant changes in vital signs or lab tests were observed. ^{1 3 4 5 6}

How is the ketone supplement treatment different from other treatments for ketosis?

The ketone supplement, specifically bis hexanoyl (R)-1,3-butanediol, is unique because it induces ketosis without requiring dietary changes, unlike traditional methods that rely on high-fat, low-carbohydrate diets. It is available in novel forms like powder and ready-to-drink beverages, which rapidly increase blood ketone levels, making it a convenient option for achieving nutritional ketosis. ^{3 4 5 7 8}

Research Team

Jeff Volek, PhD

Principal Investigator

Ohio State University

Eligibility Criteria

This trial is for individuals aged 20-70 who can fast, avoid alcohol and exercise before testing, and maintain consistent diet and medication habits. They must not have health issues that could affect study participation or interpretation of results as determined by the Investigator.

Inclusion Criteria

I am between 20 and 70 years old.

Participant has no health conditions that would prevent completion of the study requirements as judged by the Investigator based on health history

I understand the study and have signed consent forms.

Exclusion Criteria

You drink more than 3 drinks every day or more than 18 drinks each week.

I have a significant digestive condition that could affect the study's results.

My health allows me to fully participate in and understand this study.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Testing

Participants undergo a series of tests including dietary assessment, body composition measurement, and a submaximal exercise test to determine eligibility and baseline metrics.

1 day

1 visit (in-person)

Test Day

Participants consume the C8 Ketone Diester Study Product and undergo blood and urine sampling to assess ketone metabolism and tolerability.

4-5 hours

1 visit (in-person)

Follow-up

Participants are monitored for any adverse effects and overall health status after the test day.

1-2 weeks

Treatment Details

Interventions

• Beverage Tolerability Questionnaire (BTQ) and satiety visual analogue scale (Other)
• Blood Draw (Other)
• Ketone Supplement (Dietary Supplement)
• Urine Analysis (Other)

Trial Overview The study examines how different people metabolize a ketone supplement across various ages and metabolic health statuses. It involves questionnaires on beverage tolerability, blood draws to measure ketones, urine analysis, and monitoring satiety levels.

Participant Groups

Group I: C8 Ketone Supplement Experimental Treatment 4 Interventions

360mg/kg of supplement will be given on a singular testing day.

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

Buck Institute for Research on Aging

Collaborator

Trials

6

Recruited

1,200+

Findings from Research

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]

Both powdered and ready-to-drink (RTD) formulations of the novel ketone ester BH-BD effectively induce ketosis in healthy adults, increasing blood beta-hydroxybutyrate (BHB) levels within approximately 15 minutes after consumption.

The study found that a higher dose of the powdered formulation (25g) resulted in significantly greater BHB concentrations compared to lower doses and the RTD version, but both formulations were equally effective in raising BHB levels without affecting blood glucose concentrations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel Powder Formulation of the Ketone Ester, Bis Hexanoyl (R)-1,3-Butanediol, Rapidly Increases Circulating ß-Hydroxybutyrate Concentrations in Healthy Adults. Nieman, KM., Anthony, JC., Stubbs, BJ.[2023]

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]

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]

A study involving 24 healthy adults showed that consuming a ketone monoester three times a day for 28 days safely elevated blood ketone levels without affecting body weight, blood glucose, cholesterol, or kidney function.

The only reported side effect was mild nausea in a small number of instances, indicating that the ketone monoester is well-tolerated for sustained use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of sustained exogenous ketosis using ketone monoester drinks for 28 days in healthy adults. Soto-Mota, A., Vansant, H., Evans, RD., et al.[2020]

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]

Inducing experimental ketosis in calves through a diet of 1,3 butanediol for 9 to 10 days significantly raised blood levels of beta-hydroxybutyrate, indicating successful ketosis.

The ketosis led to a significant suppression of lymphocyte function, which persisted for 2 weeks, and was associated with increased susceptibility to upper respiratory infections in the calves.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suppression of mitogenic response of bovine lymphocytes during experimental ketosis in calves. Targowski, SP., Klucinski, W., Littledike, ET., et al.[2013]

References

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

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

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

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

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

A Novel Powder Formulation of the Ketone Ester, Bis Hexanoyl (R)-1,3-Butanediol, Rapidly Increases Circulating ß-Hydroxybutyrate Concentrations in Healthy Adults. [2023]

4. 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]

5. 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]

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

Safety and tolerability of sustained exogenous ketosis using ketone monoester drinks for 28 days in healthy adults. [2020]

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

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

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

Suppression of mitogenic response of bovine lymphocytes during experimental ketosis in calves. [2013]