Ketone Supplement for Alcohol Consumption Effects

Overseen By Corinde E Wiers, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: University of Pennsylvania

Must not be taking: Anticholinergics, Antipsychotics, Lithium, Psychotropics

Disqualifiers: Major psychiatric disorder, Epilepsy, Diabetes, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a ketone supplement can alter how people feel and react after consuming alcohol. Participants will visit the lab twice: once to consume a ketone supplement (known as Ketone Ester, DeltaG, or D-β-hydroxybutyric acid and R-1,3-butanediol) and once to consume a placebo. The researchers aim to determine if there is a difference in the alcohol experience. The trial seeks individuals who have consumed at least two alcoholic drinks in one sitting in the past month. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group.

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

Yes, you must refrain from using psychoactive medications or any medications that may affect study results within 24 hours of the alcohol lab procedures. If you're currently taking medications like anticholinergics, antipsychotics, lithium, or other psychotropic drugs, you may not be eligible to participate.

Will I have to stop taking my current medications?

The trial requires participants to refrain from using psychoactive medications or any medications that might affect the study results within 24 hours of the alcohol lab procedures. If you are currently taking medications that could interfere with the study or make participation hazardous, you may not be eligible to participate.

Is there any evidence suggesting that the ketone supplement is likely to be safe for humans?

Research has shown that ketone supplements are generally safe for most people. One study found that a specific type of ketone supplement, called BO-BD, was safe for older adults. It increased ketone levels without affecting blood sugar, indicating a positive safety profile.

However, some ketone supplements might not taste good and could pose challenges for individuals with liver problems. The ketone monoester, a type of supplement, contains alcohol, which might be concerning for those with liver issues.

Overall, evidence suggests that ketone supplements are safe for most people, but individuals should consider their own health conditions. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike the standard treatments for reducing alcohol consumption effects, which typically involve medications like naltrexone or acamprosate that focus on reducing cravings or withdrawal symptoms, the ketone supplement introduces a new approach. This supplement works by providing an alternative energy source for the brain through ketones, which may help stabilize mood and cognitive function after alcohol use. Researchers are excited because this method could potentially offer quicker relief and fewer side effects, tapping into the body's natural energy pathways rather than altering neurotransmitter activity. This could represent a significant shift in managing alcohol consumption effects, providing a novel option for individuals seeking support.

What evidence suggests that this ketone supplement is effective for alcohol consumption effects?

In earlier studies, ketone supplements have shown promise in reducing the urge to drink alcohol and the amount consumed. Research indicates that these supplements can ease alcohol withdrawal symptoms, making the need to drink feel less urgent. One study found that following a ketogenic diet along with ketone supplements helped lower alcohol use. This suggests that the supplement might change how the brain reacts to alcohol, possibly making it less appealing. In this trial, participants will receive either a ketone supplement or a placebo beverage. Overall, early findings suggest that ketone supplements could be a useful tool in managing the effects of alcohol. ^{3 4 6 7 8}

Who Is on the Research Team?

Corinde Wiers, PhD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

This trial is for healthy volunteers who've had at least two drinks on one occasion in the past month. They must be under 225lbs, not have a history of significant brain-related health issues, and can't be taking medications that affect brain function or interact with alcohol. Participants should not have any major psychiatric disorders (except nicotine or marijuana use disorders) and must agree to avoid psychoactive drugs before lab procedures.

Inclusion Criteria

All subjects must report at least one occasion in the prior month of drinking at least 2 drinks on a single day

Willingness to provide signed, informed consent and commit to completing the alcohol lab studies

Exclusion Criteria

Unwilling or unable to refrain from use, within 24 hours of alcohol lab procedures, psychoactive medications or medications that may affect study results

Current DSM-5 diagnosis of a major psychiatric disorder (other than nicotine use disorders, or marijuana use disorders) that could interfere with study participation or make it hazardous for the subject

Positive urine drug screen positive for all substances but marijuana on study visits (may be repeated once and if the result is negative on repeat it is not exclusionary)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive either a ketone supplement or placebo beverage followed by alcohol administration to assess subjective and objective responses

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for any side effects via phone call after each lab visit

1 day after each lab visit

2 calls (virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Ketone Supplement

Trial Overview

The study tests how a ketone supplement affects the body's response to alcohol compared to a placebo. It's conducted over two lab visits where participants consume alcohol to reach a specific breath alcohol concentration, receiving either the ketone supplement or placebo randomly during these visits.

How Is the Trial Designed?

Group I: ketone supplement Active Control 2 Interventions

Subjects will drink single dose of ketone supplement 25g

Group II: Placebo beverage Placebo Group 1 Intervention

Subjects will drink single dose of placebo beverage that will look and taste the same as ketone supplement.

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Published Research Related to This Trial

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 study involving 37 healthy volunteers revealed that the pharmacokinetics of D-β-hydroxybutyrate (BHB) from a ketone monoester drink is complex, influenced by factors such as formulation, dose, and individual characteristics like lean body weight and sex.

A population pharmacokinetic model showed that BHB absorption occurs through two phases and elimination involves both first-order and capacity-limited processes, indicating that understanding these mechanisms is crucial for optimizing ketone therapy for neurological disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Population Pharmacokinetics of D-β-hydroxybutyrate Following Administration of (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate. Shivva, V., Cox, PJ., Clarke, K., 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 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]

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 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]

Antarctic Krill Oil (AKO) significantly protects the liver from alcohol-induced injury in a rat model, as shown by improved liver histopathology and reduced serum biochemical markers after 16 weeks of alcohol administration.

AKO supplementation regulates bile acid metabolism by activating specific liver signaling pathways, leading to decreased bile acid production and altered gut microbiota, which may contribute to its protective effects against liver damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antarctic krill oil ameliorates liver injury in rats exposed to alcohol by regulating bile acids metabolism and gut microbiota. Guo, P., Xue, M., Teng, X., et al.[2022]

Nutritional ketosis, achieved through a ketogenic diet or ketone ester ingestion, may help reduce withdrawal symptoms and cravings in individuals with alcohol use disorder (AUD), based on both preclinical and clinical studies.

The mechanism behind this effect involves a shift in metabolism from glucose to acetate during alcohol intoxication, and a decline in acetate levels during withdrawal, which nutritional ketosis can help counteract.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nutritional Ketosis as a Potential Treatment for Alcohol Use Disorder. Mahajan, VR., Elvig, SK., Vendruscolo, LF., 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]

Citations

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10901540/

Ketone Supplementation Dampens Subjective and ...

A high-fat ketogenic diet and ketone supplements (KS) are efficacious in reducing alcohol craving, alcohol consumption, and signs of alcohol withdrawal.

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tandfonline.com

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1,3-Butanediol, and Its Acute Effect on ß-Hydroxybutyrate ...

The results of this study provide evidence to inform serving size selection for translation of exogenous ketone ester supplementation to target ...

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frontiersin.org

frontiersin.org/journals/physiology/articles/10.3389/fphys.2023.1195702/full

An open-label, acute clinical trial in adults to assess ketone ...

In this study, the administration of a single serving of 10 g of (R)-1,3-butanediol resulted in a peak blood BHB level of 1.2 mmol/L at 39 min, ...

4.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/38315678/

Evidence From a Preclinical Rat Study and a Randomized ...

A high-fat ketogenic diet and ketone supplements (KS) are efficacious in reducing alcohol craving, alcohol consumption, and signs of alcohol withdrawal.

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ahajournals.org

ahajournals.org/doi/10.1161/JAHA.120.020729

Ketone Ester D‐β‐Hydroxybutyrate‐(R)‐1,3 Butanediol ...

The aim of this study was to determine whether moderate elevation in D‐β‐hydroxybutyrate improves cardiac function in animals with type 2 diabetes mellitus.

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11009516/

Evaluation of the safety and tolerability of exogenous ketosis ...

On the other hand, the ketone monoester has an alcohol precursor that could limit its use in patients with liver disease and has poor palatability. More ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8234448/

Tolerability and Safety of a Novel Ketogenic Ester, Bis- ...

In this study, we determined the tolerability and safety of a novel exogenous ketone diester, bis-hexanoyl-(R)-1,3-butanediol (BH-BD), in a 28- ...

8.

sciencedirect.com

sciencedirect.com/science/article/pii/S0022227520350045

Ketone ester effects on metabolism and transcription

(R)-1,3-butanediol was chosen because this alcohol is readily converted in the liver to ketone bodies (17). This ester is readily hydrolyzed in the gut to ...