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

Trial Summary

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.

What data supports the effectiveness of the treatment Ketogenic Diet for Alcohol Metabolism?

Research suggests that a ketogenic diet may help manage alcohol withdrawal symptoms by altering brain metabolism, as seen in a study with rats. Additionally, ketogenic diets have shown benefits in weight loss and managing conditions like epilepsy and diabetes, indicating potential metabolic benefits that could be relevant for alcohol metabolism. ^{1 2 3 4 5}

Is the ketogenic diet generally safe for humans?

The ketogenic diet is generally considered safe for the general public, especially for weight loss and managing diabetes, but there are some concerns. It can cause low blood sugar (hypoglycemia) when combined with alcohol and may lead to acid-base imbalances in stressful situations. More research is needed to fully understand its long-term safety. ^{2 5 6 7 8}

How is the ketogenic diet treatment different for alcohol metabolism?

The ketogenic diet is unique because it shifts the body's energy source from glucose to ketones, which may help manage alcohol withdrawal symptoms by providing an alternative fuel for the brain. This approach is different from standard treatments that focus on medication, as it uses dietary changes to potentially improve metabolic processes affected by alcohol use. ^{2 3 9 10 11}

What is the purpose of this trial?

The research study is being conducted in health controls to better understand the effects of ketosis on brain functioning after 3 different, randomly assigned, 3-day dietary interventions and the acute effects of alcohol after consuming about 4-5 alcohol beverages. The labs visits will use magnetic resonance imaging (MRI) scans to study the brain, measuring levels of nicotinamide adenine dinucleotide (NAD), lactate, neurotransmitters glutamate, and Gamma-aminobutyric acid (GABA).

Research Team

Corinde Wiers, Ph.D.

Principal Investigator

University of Pennsylvania

Henry Kranzler, MD

Principal Investigator

University of Pennsylvania

Kyle Kampman, MD

Principal Investigator

University of Pennsylvania

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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 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]

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]

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]

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]

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]

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]

References

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

The ketogenic diet is an effective adjuvant to radiation therapy for the treatment of malignant glioma. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

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

3. England pubmed.ncbi.nlm.nih.gov

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

4. United States 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. [2023]

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

A Case of Hypoglycemia Associated With the Ketogenic Diet and Alcohol Use. [2020]

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

Another "D" in MUDPILES? A Review of Diet-Associated Nondiabetic Ketoacidosis. [2019]

7. England pubmed.ncbi.nlm.nih.gov

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

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

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

9. England pubmed.ncbi.nlm.nih.gov

Effect of diet on [lactate]/[pyruvate] ratios during alcohol metabolism in man. [2013]

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

The first case with FBXL4 mutation successfully treated with a parenteral ketogenic diet for lactic acidosis. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Acetone as biomarker for ketosis buildup capability--a study in healthy individuals under combined high fat and starvation diets. [2018]