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

Trial Summary

What is the purpose of this trial?

The research study is being conducted to better understand the effects of ketones and alcohol on brain functioning and brain metabolism. Participants will be asked to undergo three identical MRI visits after three single-dose interventions: (1) drink a ketone supplement drink, (2) drink an alcoholic beverage, (3) no intervention. These interventions will be randomly assigned (meaning everyone receives all 3 interventions, but in different orders).

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.

What data supports the effectiveness of the treatment Ketone Supplement + Alcohol for Brain Metabolism?

Research shows that ketone supplements can reduce alcohol craving and consumption, and decrease the intoxicating effects of alcohol in both humans and rats. This suggests that ketone supplements might help manage alcohol use disorder by altering how the brain responds to alcohol. ^{1 2 3 4 5}

Is the combination of ketone supplements and alcohol safe for humans?

Research suggests that ketone supplements are generally safe for humans, with some studies showing they are well-tolerated and do not cause significant side effects. However, when combined with alcohol, ketone supplements may reduce the intoxicating effects of alcohol, but more research is needed to fully understand the safety of this combination. ^{1 3 6 7 8}

How does the ketone supplement and alcohol treatment differ from other treatments for alcohol use disorder?

This treatment is unique because it combines ketone supplements with alcohol to potentially reduce the intoxicating and rewarding effects of alcohol, which is different from traditional treatments that focus on abstinence or medication to manage cravings. The ketone supplement works by altering brain metabolism, which may help decrease alcohol craving and consumption. ^{1 6 9 10 11}

Research Team

Corinde Wiers, Ph.D.

Principal Investigator

University of Pennsylvania

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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 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]

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 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]

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]

References

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

Ketone supplementation dampens subjective and objective responses to alcohol in rats and humans. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Ketogenic Diet Suppresses Alcohol Withdrawal Syndrome in Rats. [2019]

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

Ketogenic diet reduces alcohol withdrawal symptoms in humans and alcohol intake in rodents. [2022]

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

Effects of ethanol on brain metabolism. [2019]

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

Pharmacokinetic effects of a single-dose nutritional ketone ester supplement on brain ketone and glucose metabolism in alcohol use disorder - a pilot study. [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. 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]

8. Switzerland 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. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

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

10. England pubmed.ncbi.nlm.nih.gov

Impact of one-day fasting, ketogenic diet or exogenous ketones on control of energy balance in healthy participants. [2023]

11. Switzerland 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. [2021]