Ketone Supplement + Alcohol for Brain Metabolism

Overseen By Timothy Pond, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: University of Pennsylvania

Must not be taking: Anticholinergics, Antipsychotics, Psychotropics

Disqualifiers: Major psychiatric disorder, Epilepsy, Liver disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how ketones and alcohol affect brain function and metabolism. Participants will experience three different scenarios: drinking a ketone supplement (Kenetik), consuming an alcoholic beverage, and having no drink at all. Each participant will undergo these scenarios in a random order to assess their impact on the brain. Individuals who have consumed at least two alcoholic drinks in one day in the past month might be suitable for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking findings.

Do I need to stop taking my current medications for the trial?

You may need to stop taking certain medications, especially those that are psychoactive or could affect the study results, within 24 hours of the alcohol lab and MRI procedures. If you're currently taking medications that could interfere with the study or make it unsafe for you, you might not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous research has found ketone supplements to be safe and well-tolerated. Studies show that these supplements can help the body enter ketosis, where it uses ketones instead of sugar for energy. This change might improve brain function and metabolism. No major side effects were reported in these studies.

Regarding the alcoholic beverage, existing research shows that moderate alcohol consumption is generally safe for many people. However, it can affect the brain by impacting memory and problem-solving skills. The study uses a moderate amount of alcohol, designed to reach a breath alcohol level of 0.050%, considered safe for short-term use in a controlled setting.

Overall, past research has shown both the ketone supplement and the alcoholic beverage used in this study to be safe under similar conditions. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore how ketone supplements and alcohol might uniquely influence brain metabolism. Most current treatments for brain metabolism issues focus on altering neurotransmitter levels or enhancing blood flow to the brain. However, the ketone supplement, Kenetik, provides an alternative energy source for the brain, potentially bypassing some metabolic dysfunctions. Meanwhile, the alcohol treatment is carefully dosed to study its impact on metabolism without the typical negative effects of drinking. These novel approaches could offer new insights into brain energy use and potential treatment avenues.

What evidence suggests that this trial's treatments could be effective for brain metabolism?

Research has shown that ketone supplements, which participants in this trial may receive, can enhance brain function. Studies suggest that ketones improve communication between different parts of the brain. For example, one study found that a ketone drink improved thinking skills in people with mild memory issues. In contrast, alcohol, another treatment option in this trial, shows mixed results in research. Some studies suggest that moderate alcohol use might aid thinking skills, but heavy drinking can harm the brain and memory. Finding the right balance is important. ^{6 7 8 9 10}

Who Is on the Research Team?

Corinde Wiers, Ph.D.

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

This trial is for individuals who are interested in understanding how ketones and alcohol affect brain function. Participants will undergo MRI scans after consuming a ketone supplement, an alcoholic beverage, or having no intervention at all.

Inclusion Criteria

Able to provide written informed consent and commit to completing study procedures

I have had 2 or more drinks in one day in the last month.

Exclusion Criteria

I am claustrophobic.

Head trauma with loss of consciousness for more than 30 minutes (self-report, medical history)

Pregnant or breast-feeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Intervention

Participants undergo three identical MRI visits after three single-dose interventions: ketone supplement, alcoholic beverage, and no intervention.

3 visits

3 visits (in-person)

Follow-up

Participants receive a follow-up phone call to ask about any changes to their health and to ensure no side effects from the MRI scan or other procedures.

1 day

1 call (virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Alcohol beverage
• Kenetik

Trial Overview

The study tests the effects of a single dose of a ketone supplement (Kenetik) and an alcoholic beverage on brain metabolism by comparing them to no intervention using MRI technology. Each participant will experience all three scenarios in random order.

How Is the Trial Designed?

Group I: Ketone Supplement Experimental Treatment 1 Intervention

Subjects will receive ketone supplement once by mouth, 20g of kentones.

Group II: Alcohol beverage Experimental Treatment 1 Intervention

Alcohol lab, participants will receive ethanol drinks that are dose-adjusted for body weight and sex differences in pharmacokinetics and calculated to obtain a final breath alcohol concentration of 0.050%

Group III: No Intervention Active Control 1 Intervention

No intervention will be given

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Published Research Related to This Trial

In a study involving 33 inpatients with alcohol use disorder, those on a ketogenic diet (KD) required fewer benzodiazepines during detoxification compared to those on a standard American diet, suggesting that KD may help reduce withdrawal severity.

The KD not only altered brain metabolism by increasing ketones and glutamate while lowering neuroinflammatory markers but also showed potential in reducing alcohol cravings and consumption, as evidenced by a rat model of alcohol dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketogenic diet reduces alcohol withdrawal symptoms in humans and alcohol intake in rodents. Wiers, CE., Vendruscolo, LF., van der Veen, JW., et al.[2022]

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]

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]

The ketone monoester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate effectively elevates blood ketone levels in healthy volunteers, reaching maximum plasma concentrations of 3.30 mM for β-hydroxybutyrate within 1-2 hours after ingestion.

This ketone monoester was generally well-tolerated over a 5-day period, although some gastrointestinal side effects were noted at higher doses, indicating it is a safe alternative to traditional ketogenic diets for enhancing physical and cognitive performance.

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]

In a study with 10 healthy participants, ketone supplements (KS) significantly reduced breath alcohol concentration (BrAC) and blood alcohol levels (BAL) after alcohol consumption, indicating a potential to lessen the intoxicating effects of alcohol.

In a parallel study with rats, KS also lowered BAL more effectively than water or a sweetener, suggesting that ketones may alter both physiological and subjective responses to alcohol, making them a promising intervention for alcohol use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketone supplementation dampens subjective and objective responses to alcohol in rats and humans. Li, X., Shi, Z., Todaro, D., et al.[2023]

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]

In a study of obese adults consuming low-calorie ketogenic drinks for two weeks, both the 4:1 and 1.7:1 ketogenic ratios effectively maintained elevated blood ketone levels, indicating successful ketosis induction.

All groups experienced significant weight and body fat loss, while the ketogenic drink groups also showed improved blood lipid profiles and reduced appetite, suggesting potential for ketogenic nutrition in obesity treatment and other health conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-Week Exclusive Supplementation of Modified Ketogenic Nutrition Drink Reserves Lean Body Mass and Improves Blood Lipid Profile in Obese Adults: A Randomized Clinical Trial. Choi, HR., Kim, J., Lim, H., et al.[2023]

Oral administration of the ketone ester (KE) significantly increases ketosis levels in non-fasted mice, reaching a peak of 6.83 mmol/L within 30 minutes, indicating its rapid effectiveness in generating ketone bodies.

The study reveals that KE enhances brain metabolism by increasing acetyl-CoA and citric cycle intermediates, which may inhibit glycolysis and suggest a potential therapeutic role for KE in acute neurological diseases.

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]

A preclinical study using male Sprague Dawley rats indicated that a ketogenic diet significantly reduced symptoms of alcohol withdrawal, such as rigidity and irritability, after alcohol administration.

This research suggests that a ketogenic diet could be a novel and effective strategy for managing alcohol withdrawal symptoms during detoxification in humans, addressing a critical gap in current treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketogenic Diet Suppresses Alcohol Withdrawal Syndrome in Rats. Dencker, D., Molander, A., Thomsen, M., et al.[2019]

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