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

10 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a single blinded, randomized trial to evaluate the immediate subjective and objective effects of alcohol after a dose ketone supplement compared to a placebo in 10 health volunteers. Subjects will complete 2 lab visits where they consume a dose of alcohol (based on weight), to bring their breath alcohol concentration to about 0.050%. Participants will randomly receive ketone supplement at one lab and the placebo at the next lab.

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.

What data supports the idea that Ketone Supplement for Alcohol Consumption Effects is an effective treatment?

The available research shows that ketone supplements can reduce alcohol craving, consumption, and withdrawal symptoms. In a study with humans and rats, ketone supplements lowered blood alcohol levels and reduced the desire for alcohol. Another study found that a ketogenic diet, which increases ketone levels, helped reduce alcohol withdrawal symptoms and cravings. Compared to a standard diet, the ketogenic diet required fewer medications for withdrawal symptoms and reduced alcohol intake in rats. This suggests that ketone supplements could be a promising treatment for alcohol use disorder. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment Ketone Supplement for reducing alcohol consumption effects?

Research shows that ketone supplements can reduce alcohol craving, consumption, and withdrawal symptoms. In both humans and rats, ketone supplements lowered blood alcohol levels and reduced the desire for alcohol, suggesting they might help manage alcohol use disorder. ^{1 2 3 4 5}

What safety data exists for ketone supplements used to reduce alcohol consumption effects?

Several studies have evaluated the safety and tolerability of ketone supplements, including ketone esters and ketone salts. These studies generally show that ketone supplements are safe and well-tolerated in healthy adults. Mild gastrointestinal effects were reported at higher doses, but no clinically meaningful changes in safety measures such as vital signs and laboratory tests were observed. Ketone supplements have been shown to elevate blood ketone levels effectively without significant adverse effects, making them a practical option for achieving ketosis. ^{1 4 6 7 8}

Is the ketone supplement safe for human use?

Research shows that ketone supplements, including ketone esters and ketone salts, are generally safe and well-tolerated in healthy adults. Some mild side effects like gastrointestinal discomfort and nausea have been reported, but no serious safety concerns were identified in studies lasting up to 28 days. ^{1 4 6 7 8}

Is the ketone supplement a promising treatment for reducing the effects of alcohol consumption?

Yes, the ketone supplement shows promise as a treatment for reducing the effects of alcohol consumption. It can lower the levels of alcohol in the blood, make alcohol less enjoyable, and help reduce cravings and withdrawal symptoms. This suggests it could be a new way to help people with alcohol use disorder. ^{1 3 4 7 9}

How does ketone supplementation differ from other treatments for alcohol use disorder?

Ketone supplementation is unique because it reduces the intoxicating and rewarding effects of alcohol by altering physiological and subjective responses, unlike traditional treatments that may focus on withdrawal symptoms or liver protection. This approach uses ketones to potentially reduce alcohol craving and consumption, offering a novel intervention for alcohol use disorder. ^{1 3 4 7 9}

Research Team

Corinde Wiers, PhD

Principal Investigator

University of Pennsylvania

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

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]

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 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]

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]

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]

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]

References

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

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

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

Nutritional Ketosis as a Potential Treatment for Alcohol Use Disorder. [2022]

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

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

4. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

The Population Pharmacokinetics of D-β-hydroxybutyrate Following Administration of (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

On the Metabolism of Exogenous Ketones in Humans. [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. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

Antarctic krill oil ameliorates liver injury in rats exposed to alcohol by regulating bile acids metabolism and gut microbiota. [2022]