Ketogenic Diet for Brain Cancer

Overseen By Madison Kackley, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Ohio State University Comprehensive Cancer Center

Disqualifiers: Whole brain radiation, Pregnancy, Small cell lung carcinoma, Leptomeningeal disease, Type 1 diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

24 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the ketogenic diet treatment for brain cancer?

Research suggests that a ketogenic diet, which is high in fat and low in carbohydrates, may help slow the growth of brain cancer by reducing the availability of glucose, which cancer cells need to grow. Some studies have shown that this diet can be effective in mice and has shown promise in human case reports, particularly when combined with other treatments. ^{1 2 3 4 5}

Is the ketogenic diet safe for humans?

The ketogenic diet has been studied in various conditions and is generally considered safe for humans, though some people may experience side effects like changes in cholesterol levels, constipation, and fatigue. In a study of older adults, 15% experienced adverse events, but many found the diet beneficial for weight loss, glucose control, and cancer outcomes. ^{3 6 7 8 9}

How does the ketogenic diet treatment differ from other treatments for brain cancer?

The ketogenic diet is unique because it targets the energy metabolism of brain cancer cells by restricting glucose, which these cells rely on for growth. Unlike standard treatments that may provide glucose, this high-fat, low-carb diet reduces glucose availability, potentially slowing tumor growth and improving patient outcomes. ^{1 3 10 11 12}

What is the purpose of this trial?

This pilot study will be a single center, randomized controlled study of 24 participants with diagnosed BM (various primary disease sites) comparing the effect of a ketogenic (n=12) and AICR (n=12) diet. Potential participants will be identified via medical record reviews and chart reviews. Eligibility of patients will be assessed via medical record review. Randomization will be balanced by blocks of random sizes but no stratification due to the small sample size. Both groups will undergo a 16-week diet intervention where research dietitians will provide educations, recipes and grocery lists on the participants assigned diet. Each group will receive 4-7 days worth of food prior to testing days to both aid in transitioning to each dietary arm and to ensure that the metabolic needs for each arm are met. In an effort to maintain a patient centric focus and monitor changes in quality of life (QOL) all patients will complete psychosocial and behavioral inventories. These inventories aim to capture a holistic view on the proposed nutritional intervention during treatment. Primary outcomes will be determined at baseline, 8 weeks, and 16 weeks while patient-centric outcomes will be assessed every four weeks. Participants will have counseling by the attending physician for additional applicable medications for any treatment related side effects or toxicities. The intervention groups will undergo their randomized dietary regimen for 16 weeks.

Research Team

Jeff Volek, PhD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Eligibility Criteria

This trial is for adults with brain tumors who have measurable lesions, are in good physical condition (able to perform normal activities or are mostly ambulatory), and can follow a special diet. They should not be undergoing whole brain radiation, pregnant, nursing, or have certain conditions like Type 1 diabetes or severe kidney issues.

Inclusion Criteria

My brain tumor prognosis score is above 1.5.

I am mostly active but may have some symptoms.

I am scheduled for stereotactic radiosurgery (SRS).

Exclusion Criteria

I have never had cancer spread to the lining of my brain and spinal cord.

I have diabetes and need insulin.

I am unable to understand or sign the consent form.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Diet Intervention

Participants undergo a 16-week diet intervention with either a ketogenic or AICR diet, including education, recipes, and grocery lists provided by research dietitians.

16 weeks

Regular visits for diet monitoring and support

Follow-up

Participants are monitored for safety, effectiveness, and quality of life after the diet intervention.

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• Ketogenic Diet

Trial Overview The Keto-Brain study compares the effects of a ketogenic diet versus an AICR diet on patients with brain metastases over 16 weeks. Participants will receive dietary guidance and food supplies from research dietitians and complete regular health questionnaires.

Participant Groups

Group I: Standard of Care + Ketogenic Diet Experimental Treatment 5 Interventions

(standard of care, ketogenic diet) Patients receive standard of care with SRS. Patients undergo a controlled feeding period ketogenic diet comprising of meals for the first week and then transition into a free living with guided support type of intervention.

Group II: Standard of Care Active Control 4 Interventions

Patients receive standard of care therapy with SRS and AICR Diet education.

Who Is Running the Clinical Trial?

Ohio State University Comprehensive Cancer Center

Lead Sponsor

Trials

350

Recruited

295,000+

Findings from Research

A ketogenic diet (KD) combined with standard treatments for aggressive primary brain tumors (APBT) showed promising results, with three younger patients surviving significantly longer (52-74 months) compared to older patients, who had an average survival of 8 months after diagnosis.

The study demonstrated that it is feasible to maintain dietary-induced ketosis in patients with APBT, suggesting that further research is needed to explore the potential benefits of KD, particularly in younger patients under 40.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long Term Survivals in Aggressive Primary Brain Malignancies Treated With an Adjuvant Ketogenic Diet. Schwartz, KA., Noel, M., Nikolai, M., et al.[2023]

The pilot study of a 4:1 ketogenic diet (KD) using a total meal replacement program for glioblastoma (GBM) patients showed that the diet was well tolerated, with mild and transient treatment-emergent adverse events, and 62.5% of participants completed the 6-month treatment.

Survival times were promising, with a mean of 20 months for newly diagnosed patients and 12.8 months for recurrent GBM patients after starting the KD, suggesting potential benefits, although the small sample size limits definitive conclusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of glioblastoma multiforme with "classic" 4:1 ketogenic diet total meal replacement. Klein, P., Tyrlikova, I., Zuccoli, G., et al.[2020]

The restricted ketogenic diet (RKD) targets energy metabolism in malignant brain cancer by reducing glucose and glutamine availability, which are crucial for tumor growth, and has shown anti-cancer effects in mouse models.

Case reports indicate that the RKD can be an effective non-toxic treatment option for malignant gliomas in humans, potentially enhancing the efficacy of existing therapies that also target glucose and glutamine metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is the restricted ketogenic diet a viable alternative to the standard of care for managing malignant brain cancer? Seyfried, TN., Marsh, J., Shelton, LM., et al.[2017]

A modified ketogenic diet (MKD) was well tolerated by glioma patients, with only minor side effects like constipation reported, and it was achievable within a standard healthcare service.

Out of 172 surveyed patients, 69% supported offering MKD as a treatment option, and 73% expressed willingness to try it for 3 months, indicating strong interest in future clinical trials to assess its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Modified Ketogenic Diet in Adults with Glioblastoma: An Evaluation of Feasibility and Deliverability within the National Health Service. Martin-McGill, KJ., Marson, AG., Tudur Smith, C., et al.[2022]

A review of 13 studies involving 187 glioma patients indicates that ketogenic diets (KD) may inhibit glioma growth and help manage symptoms, but there is significant variability in how these diets are implemented.

The lack of standardization in ketogenic diet protocols for glioma patients complicates comparisons of their effectiveness, highlighting the need for a consensus on dietary definitions and methods to optimize treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methodological Approaches to Ketogenic Dietary Treatments in Glioma Patients from a Nutritional Point of View. Guo, A., Asztely, F., Smits, A., et al.[2022]

The ERGO2 trial, involving 50 patients with recurrent brain tumors, found that a calorie-restricted ketogenic diet combined with intermittent fasting did not improve progression-free survival compared to a standard diet, despite achieving significant metabolic changes in those on the ketogenic diet.

Patients on the ketogenic diet successfully met their dietary goals, leading to notable decreases in leptin and insulin levels, while low glucose levels were identified as a potential marker for better prognosis, although quality of life and cognitive function remained unaffected.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term fasting in glioma patients: analysis of diet diaries and metabolic parameters of the ERGO2 trial. Voss, M., Wenger, KJ., von Mettenheim, N., et al.[2022]

The restricted KetoCal diet significantly reduced tumor growth in mouse models of malignant brain cancer, decreasing growth by about 65% for CT-2A tumors and 35% for U87-MG tumors, while also improving overall health and survival compared to a standard high carbohydrate diet.

KetoCal's effectiveness is attributed to its ability to lower plasma glucose levels and increase ketone bodies, exploiting the tumors' reliance on glucose for energy, suggesting that this diet could be a safe and effective alternative therapy for managing malignant brain cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer. Zhou, W., Mukherjee, P., Kiebish, MA., et al.[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]

The ketogenic dietary intervention, known as the Glioma Atkins-Based Diet (GLAD), was feasible and safe for 25 patients with glioma, with 84% completing the 8-week study and significant metabolic changes observed, including increased ketone levels in the brain.

The diet led to meaningful systemic changes, such as decreased insulin and hemoglobin A1c levels, and increased ketone concentrations in both the tumor and healthy brain tissue, suggesting that ketonuria is a reliable indicator of metabolic activity in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and Biological Activity of a Ketogenic/Intermittent-Fasting Diet in Patients With Glioma. Schreck, KC., Hsu, FC., Berrington, A., et al.[2022]

The calorically restricted ketogenic diet (CRKD) shows promise as an alternative therapy for brain cancer, effectively managing tumor growth in both animal models and patients.

The CRKD may work through several mechanisms, including reducing blood vessel formation (antiangiogenic), decreasing inflammation (anti-inflammatory), and promoting cell death in tumor cells (proapoptotic), which is particularly relevant since brain tumor cells struggle to use ketone bodies for energy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting energy metabolism in brain cancer with calorically restricted ketogenic diets. Seyfried, TN., Kiebish, M., Mukherjee, P., et al.[2017]

A ketogenic diet (KD) was found to be feasible and safe for patients undergoing standard chemoradiation treatment for glioblastoma multiforme, with no severe adverse effects reported during the study.

Of the 11 patients who started the study, 67% completed the KD protocol, and overall survival ranged from 9.8 to 19.0 months, suggesting potential benefits that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketogenic diet treatment as adjuvant to standard treatment of glioblastoma multiforme: a feasibility and safety study. van der Louw, EJTM., Olieman, JF., van den Bemt, PMLA., et al.[2022]

In a case series of 12 patients with central nervous system malignancies, those who followed a ketogenic diet for 120 days showed maintained ketone levels and decreased glucose levels, suggesting a potential metabolic advantage in managing their condition.

Patients reported improved symptoms and imaging indicated better disease control and reduced swelling, highlighting the need for further structured clinical trials to explore the efficacy of the ketogenic diet as an adjunct therapy for CNS tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploring the Feasibility and Effects of a Ketogenic Diet in Patients With CNS Malignancies: A Retrospective Case Series. Panhans, CM., Gresham, G., Amaral, LJ., et al.[2020]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Long Term Survivals in Aggressive Primary Brain Malignancies Treated With an Adjuvant Ketogenic Diet. [2023]

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

Treatment of glioblastoma multiforme with "classic" 4:1 ketogenic diet total meal replacement. [2020]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Is the restricted ketogenic diet a viable alternative to the standard of care for managing malignant brain cancer? [2017]

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

The Modified Ketogenic Diet in Adults with Glioblastoma: An Evaluation of Feasibility and Deliverability within the National Health Service. [2022]

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

Methodological Approaches to Ketogenic Dietary Treatments in Glioma Patients from a Nutritional Point of View. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

Short-term fasting in glioma patients: analysis of diet diaries and metabolic parameters of the ERGO2 trial. [2022]

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

The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer. [2020]

8. 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]

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

Feasibility and Biological Activity of a Ketogenic/Intermittent-Fasting Diet in Patients With Glioma. [2022]

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

Targeting energy metabolism in brain cancer with calorically restricted ketogenic diets. [2017]

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

Ketogenic diet treatment as adjuvant to standard treatment of glioblastoma multiforme: a feasibility and safety study. [2022]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Exploring the Feasibility and Effects of a Ketogenic Diet in Patients With CNS Malignancies: A Retrospective Case Series. [2020]