Ketogenic Diet for Alcohol Metabolism

(KAM Trial)

Overseen By Timothy S Pond, MPH

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

Compensation: Varies

Number of Visits: 6

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a ketogenic diet (a low-carb, high-fat diet) affects the brain, particularly after alcohol consumption. Researchers aim to understand brain function during ketosis (when the body burns fat for fuel) and after alcohol intake. Participants will follow different diets, including a control diet, a ketogenic diet, and a ketone supplement (a type of dietary supplement), while undergoing MRI brain scans. The study seeks individuals who have consumed two or more alcoholic drinks in a single day at least once in the past month. As a Phase 2, Phase 3 trial, it measures the ketogenic diet's effectiveness in an initial group and represents the final step before FDA approval, offering participants a chance to contribute to important research.

Will I have to stop taking my current medications?

The trial requires participants to refrain from using psychoactive medications or any medication that may affect study results within 24 hours of the alcohol lab procedures. Additionally, 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 this trial's treatments are likely to be safe?

Research has examined the ketogenic diet's impact on alcohol cravings and withdrawal symptoms during detox. It has been found to reduce cravings and lessen withdrawal severity. However, concerns exist about long-term effects, such as increased cholesterol levels and issues with fat metabolism. Additionally, prolonged use of a ketogenic diet with alcohol may affect blood sugar levels.

Studies on ketone supplements, which raise blood ketone levels without reducing carbs, indicate they are generally safe and well-tolerated in healthy adults. Some individuals have reported mild stomach issues with higher doses.

Overall, both the ketogenic diet and ketone supplements are considered relatively safe for short-term use in healthy adults, though some possible side effects should be noted. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike traditional treatments for alcohol use disorders that often involve medications like naltrexone or acamprosate, the ketogenic diet offers a dietary approach to influence alcohol metabolism. Researchers are excited about this because the ketogenic diet can potentially alter how the body processes alcohol by shifting energy sources from carbohydrates to fats. Additionally, the use of a ketone supplement alongside a control diet provides a novel way to examine the impact of ketones on alcohol metabolism. This could lead to new insights into non-pharmacological methods to manage alcohol consumption and its effects.

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

Research has shown that a ketogenic diet, which participants in this trial may follow, might help reduce the urge to drink and ease withdrawal symptoms in people with alcohol use problems. One study found that people on this diet had fewer cravings and milder withdrawal symptoms during detox. Another study discovered that being in a state of nutritional ketosis (a condition from eating a low-carb diet) could lower alcohol consumption in animals.

In this trial, some participants will receive ketone supplements, which have been found to reduce alcohol cravings and lessen alcohol's effects. Early evidence suggests these supplements might change how the brain uses sugar, potentially reducing alcohol's impact. This trial studies both the ketogenic diet and ketone supplements for their potential in addressing alcohol-related issues. ^{1 2 3 5 6}

Who Is on the Research Team?

Henry Kranzler, MD

Principal Investigator

University of Pennsylvania

Kyle Kampman, MD

Principal Investigator

University of Pennsylvania

Corinde Wiers, Ph.D.

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

This trial is for healthy individuals who have consumed at least two alcoholic drinks on one occasion in the past month. They must be willing to follow study procedures and diets, not exceed a weight of 225lbs, and can't be using medications or substances that affect the study. Pregnant or breastfeeding women, those with certain medical conditions or psychiatric disorders, and anyone with MRI contraindications are excluded.

Inclusion Criteria

Willingness to provide signed, informed consent and commit to completing study procedures.

You have consumed two or more alcoholic drinks in a day at least once in the month before agreeing to participate.

Exclusion Criteria

You weigh more than 225 pounds, and we need to limit the amount of alcohol you can have based on your weight.

I've had a severe head injury with loss of consciousness, skull fracture, or abnormal MRI results.

You have a major psychiatric disorder, like depression or schizophrenia, that could make it unsafe for you to take part in the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Dietary Intervention

Participants undergo three different 3-day dietary interventions, each followed by a lab visit on day 4

9 days (3 days per intervention, spaced 1 week apart)

3 lab visits (in-person)

Alcohol Intervention

Participants receive ethanol drinks to elevate breath alcohol levels to approximately 0.08% to measure acute effects

1 day per intervention

3 lab visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the interventions

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ethanol
• Ketogenic diet
• Ketone Supplement

Trial Overview The study tests how a ketogenic diet affects brain function during ketosis and after consuming alcohol (4-5 beverages). Participants will undergo three different dietary interventions over three days each: a ketogenic diet, ethanol intake, ketone supplements, versus a control diet. Brain activity is monitored using MRI scans.

How Is the Trial Designed?

Group I: Ketone supplement Experimental Treatment 2 Interventions

Eat a control diet for 3 days with a ketone supplement drink

Group II: Ketogenic diet Experimental Treatment 1 Intervention

Eat a ketogenic diet for 3 days

Group III: Alcohol Intervention Experimental Treatment 3 Interventions

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 0.08%

Group IV: Control Diet Placebo Group 1 Intervention

Eat a control diet for 3 days

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

Ketogenic diets, which are low in carbohydrates and high in fats, have been shown to be effective for weight loss and can improve triglyceride and HDL cholesterol levels compared to low-fat diets.

Despite concerns about their high fat content, the degree of carbohydrate restriction needed to achieve ketosis is still unclear, indicating a need for more standardized research on these diets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketogenic diets for weight loss: A review of their principles, safety and efficacy. Sumithran, P., Proietto, J.[2022]

The ketogenic diet, which is high in fat and low in carbohydrates and protein, has proven to be very effective in treating intractable epilepsy, particularly in children who do not respond to standard antiepileptic drugs.

There is emerging evidence that the ketogenic diet may also benefit infants, adolescents, and adults with drug-resistant epilepsy, suggesting its potential as a broader treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of the ketogenic diet as a treatment for epilepsy refractory to drug treatment. Murphy, P.[2007]

In a mouse model of malignant glioma, a ketogenic diet (KetoCal®) significantly increased survival by approximately 5 days compared to a standard diet, indicating its potential as a supportive treatment in cancer therapy.

The combination of the ketogenic diet and radiation therapy showed more than additive effects, with tumor growth significantly reduced in most mice on the ketogenic diet, suggesting that metabolic changes from the diet could enhance the effectiveness of conventional cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The ketogenic diet is an effective adjuvant to radiation therapy for the treatment of malignant glioma. Abdelwahab, MG., Fenton, KE., Preul, MC., et al.[2022]

In a study involving 10 subjects, intravenous alcohol infusion after a low-carbohydrate, high-fat diet resulted in significantly higher blood lactate/pyruvate ratios during fasting alcohol metabolism.

The findings suggest that the balance of carbohydrates and fats in the diet can influence how the body metabolizes alcohol, potentially affecting the transfer of NADH between the cytoplasm and mitochondria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of diet on [lactate]/[pyruvate] ratios during alcohol metabolism in man. Mascord, D., Rogers, J., Smith, J., et al.[2013]

A 4-year-old girl with a rare FBXL4 gene mutation and severe lactic acidosis was successfully treated with a ketogenic diet (KD) after standard treatments failed, highlighting the KD's potential in managing mitochondrial disorders.

This case represents the first documented use of parenteral KD to effectively reduce lactic acidosis in a patient with mitochondrial depletion syndrome, suggesting a promising nonpharmacological intervention for similar conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The first case with FBXL4 mutation successfully treated with a parenteral ketogenic diet for lactic acidosis. İnci, A., Aktaş, E., Cengiz Ergin, FB., et al.[2022]

While ketogenic diets are generally safe and effective for weight loss and diabetes management, they can lead to dangerous acid-base disturbances under stress due to excessive ketone production.

The article presents a unique case of ketoacidosis linked to the Atkins diet, raising concerns about the long-term safety of ketogenic diets and highlighting the need for awareness of potential risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Another "D" in MUDPILES? A Review of Diet-Associated Nondiabetic Ketoacidosis. Ullah, W., Hamid, M., Mohammad Ammar Abdullah, H., et al.[2019]

Ketogenic diets, which consist of over 70% fat and very low carbohydrates, may be more effective than low-fat diets for treating obesity and diabetes, showing potential benefits in reducing blood glucose and insulin levels.

A well-formulated ketogenic diet appears to be safe for the general public and could be considered a first-line treatment for obesity and diabetes, although more high-quality clinical trials are needed to explore its long-term effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Ketogenic Diet: Evidence for Optimism but High-Quality Research Needed. Ludwig, DS.[2023]

A case study of a 69-year-old woman on a ketogenic diet for nearly a year revealed severe hypoglycemia (blood glucose of 39 mg/dL) after alcohol consumption, highlighting potential risks associated with long-term adherence to this diet.

The case suggests that the ketogenic diet may disrupt normal glucose regulation, leading to hypoglycemia that might not present with typical symptoms, indicating a need for caution regarding alcohol intake while following this diet.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Case of Hypoglycemia Associated With the Ketogenic Diet and Alcohol Use. Spoke, C., Malaeb, S.[2020]

In a study of 200 older patients (median age 70) on a ketogenic diet, 67% reported beneficial outcomes, including significant weight loss for 79% of those seeking it, improved glucose control for 54% of those with diabetes, and positive effects on cancer outcomes for 63% of patients pursuing that goal.

While the ketogenic diet showed promise for various health issues in older adults, 15% of participants experienced adverse events, including dyslipidemia and constipation, highlighting the need for careful monitoring in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can older patients adopt and maintain a ketogenic diet? An observational study in support of clinical trials in older patients. Almodallal, Y., Cook, K., Lammert, LM., 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 11 healthy individuals, a high-fat diet (79% or 90% fat) significantly increased ketone levels during fasting compared to a mixed diet (29% fat), indicating that higher fat intake enhances the body's ability to produce ketones.

Participants with higher resting energy expenditure and lower body mass index showed a greater capacity for ketone buildup during fasting, suggesting that individual metabolic factors can influence the effectiveness of ketogenic diets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acetone as biomarker for ketosis buildup capability--a study in healthy individuals under combined high fat and starvation diets. Prabhakar, A., Quach, A., Zhang, H., et al.[2018]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK499830/

Ketogenic Diet - StatPearls - NCBI Bookshelf Compared to low-fat diets, the ketogenic diet demonstrated superior outcomes in terms of glycemic control, weight loss, and lipid markers.[23] ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2589004224025161

The impact of a ketogenic diet on weight loss, metabolism ... We found positive effects of KD in both intervention groups: significant weight loss was achieved by reducing body fat mass without affecting ...

3. frontiersin.org frontiersin.org/journals/nutrition/articles/10.3389/fnut.2024.1254341/full

Ketogenic diet reduces a neurobiological craving signature ... We recently found that a KD intervention reduced alcohol withdrawal severity and alcohol craving in individuals with an AUD undergoing inpatient detoxification, ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8670944/

Nutritional Ketosis as a Potential Treatment for Alcohol Use ... There is evidence that KD and KE reduce appetite and food intake (15, 46) and rodent studies have shown that nutritional ketosis reduces alcohol intake. Rats ...

5. nature.com nature.com/articles/s41392-021-00831-w

Ketogenic diet for human diseases: the underlying ... Very-low-carbohydrate diets could improve glycemic control, HbA1c levels, and lipid markers in obese individuals before obvious weight loss ...

6. academic.oup.com academic.oup.com/jes/article/4/6/bvaa045/5821589

A Case of Hypoglycemia Associated With the Ketogenic Diet ... This case illustrates that adherence to a ketogenic diet for a prolonged period of time, in combination with alcohol intake, can disrupt normal glucose ...