Ketone Ester for Microbiome Health

(BREAK Trial)

Overseen By John C Newman, MD, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Francisco

Must not be taking: Opioids, Antidiarrheals, Antispasmodics, others

Disqualifiers: Cancer, Uncontrolled cardiac, Gastrointestinal, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 7 days

20 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this observational study is to learn if a ketone ester can improve the content of the gut microbiome. The main questions it aims to answer are: * Does a ketone ester reduce age-related signatures in the gut microbiome? * What changes occur in the gut microbiome after consuming a ketone ester? Participants will: * Take a ketone ester drink every day for seven (7) days * Collect and ship stool samples within seven (7) days before, during, and within seven (7) days after the study period * Measure their ketone levels with a urine strip every day after having the drink * Answer questions about their typical diet on a normal day * Record their symptoms, if any arise

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 does exclude those who have used medications affecting gut function within 30 days before starting. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the treatment exogenous ketone ester for microbiome health?

The research suggests that altering the gut microbiome can have health benefits, as seen in studies where dietary interventions and microbiome modulators like prebiotics improved gut health. Although not directly about ketone esters, these findings imply that similar treatments could potentially influence microbiome health. ^{1 2 3 4 5}

How does the ketone ester treatment differ from other treatments for microbiome health?

The ketone ester treatment is unique because it involves the use of exogenous ketones, specifically 3-hydroxybutyrate (3HB), which can improve gut health by altering the gut microbiome and systemic metabolic status. Unlike traditional dietary changes, this treatment directly donates ketones to the gut, acting as a prebiotic to enhance the gut environment. ^{6 7 8 9 10}

Research Team

John C Newman, MD, PhD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for healthy adults interested in the potential benefits of a ketone ester on gut health. Participants will need to be comfortable with daily drink consumption, urine testing, and stool sample collection over a week.

Inclusion Criteria

My BMI is between 18.5 and 39.9.

Subject has an email address and internet access via computer, phone, or other device, and is willing and able to maintain internet access throughout the trial to complete virtual visits via video conference and electronic questionnaires

Subject has no health conditions that would prevent them from fulfilling the study requirements as judged by the Clinical Investigator on the basis of medical history and routine laboratory test results

Exclusion Criteria

Subject has been hospitalized within 30 days of Virtual Visit 1

I am currently being treated for cancer, under surveillance, or was diagnosed within the last two years, excluding non-melanoma skin cancer.

I have taken antibiotics within the last 60 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

Treatment

Participants take a ketone ester drink every day for seven days and collect stool samples

7 days

Daily self-administration and sample collection

Follow-up

Participants are monitored for changes in microbiome composition and tolerability symptoms

2 weeks

Sample collection and symptom recording

Treatment Details

Interventions

• Exogenous ketone ester

Trial Overview The study investigates if consuming a ketone ester drink daily for six days can positively alter the gut microbiome and reduce age-related changes. It involves tracking diet, monitoring ketones via urine tests, and analyzing stool samples before, during, and after intake.

Participant Groups

Group I: 25g Bis-octanoyl-(R)-1,3-butanediol (C8) Experimental Treatment 1 Intervention

Participants will receive 25g of the ketone ester bis-octanoyl-(R)-1,3-butanediol (C8) daily.

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Findings from Research

3-Hydroxybutyrate (3HB) has the potential to enhance gut health by regulating the gut microbiome and promoting stem cell expansion, suggesting its role as a key player in gut physiology.

Using poly-hydroxybutyrate (PHB) as a prebiotic can effectively donate 3HB to the gut, potentially improving the gut environment and maintaining microbiome integrity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New prebiotics by ketone donation. Satoh, T.[2023]

Ketogenic diets (KDs) significantly alter gut microbiota composition, specifically leading to a depletion of bifidobacteria, which is distinct from the effects of high-fat diets (HFDs).

Ketone bodies produced during KDs inhibit the growth of bifidobacteria and are associated with a reduction in pro-inflammatory Th17 cells in the gut, suggesting that KDs may have anti-inflammatory effects through microbiome modulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketogenic Diets Alter the Gut Microbiome Resulting in Decreased Intestinal Th17 Cells. Ang, QY., Alexander, M., Newman, JC., et al.[2022]

The engineered probiotic Escherichia coli Nissle 1917 (EcN) successfully produced the ketone body (R)-3-hydroxybutyrate (3HB) in the guts of mice, significantly increasing levels of beneficial short-chain fatty acids and promoting the growth of healthy gut bacteria.

This modified EcN (EcNL4) effectively improved symptoms of colitis in mice, outperforming both wild-type EcN and direct 3HB administration in various health markers, suggesting a novel approach for treating colonic diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Construction of a sustainable 3-hydroxybutyrate-producing probiotic Escherichia coli for treatment of colitis. Yan, X., Liu, XY., Zhang, D., et al.[2023]

Two validated LC-MS methods were developed to accurately measure ketone ester and its metabolites in human plasma, ensuring reliable pharmacokinetic profiling for potential therapeutic use.

The study found that ketone ester undergoes non-saturable metabolism in human plasma, indicating its metabolic stability at high concentrations, and that human serum albumin plays a role in its metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative Determination of (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate (Ketone Ester) and Its Metabolites Beta-hydroxybutyrate, 1-3-Butanediol, and Acetoacetate in Human Plasma Using LC-MS. Panse, N., Halquist, M., Gerk, PM.[2023]

References

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

An In Vitro Batch-culture Model to Estimate the Effects of Interventional Regimens on Human Fecal Microbiota. [2021]

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

Bile acid sequestration reverses liver injury and prevents progression of nonalcoholic steatohepatitis in Western diet-fed mice. [2021]

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

Gut microbiome-targeted therapies in nonalcoholic fatty liver disease: a systematic review, meta-analysis, and meta-regression. [2023]

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

An Integrated Metabolomic and Microbiome Analysis Identified Specific Gut Microbiota Associated with Fecal Cholesterol and Coprostanol in Clostridium difficile Infection. [2020]

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

Individualized Responses of Gut Microbiota to Dietary Intervention Modeled in Humanized Mice. [2020]

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

New prebiotics by ketone donation. [2023]

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

Ketogenic Diets Alter the Gut Microbiome Resulting in Decreased Intestinal Th17 Cells. [2022]

8. China pubmed.ncbi.nlm.nih.gov

Construction of a sustainable 3-hydroxybutyrate-producing probiotic Escherichia coli for treatment of colitis. [2023]

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

Quantitative Determination of (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate (Ketone Ester) and Its Metabolites Beta-hydroxybutyrate, 1-3-Butanediol, and Acetoacetate in Human Plasma Using LC-MS. [2023]

10. Poland pubmed.ncbi.nlm.nih.gov

Effects of dietary components on intestinal short-chain fatty acids (SCFAs) synthesis in healthy adult persons following a ketogenic diet. [2022]