The Study

Glioblastoma multiforme (GBM) is the most common and malignant of the adult brain cancers. Generally, less than 20% of younger adults with this cancer survive beyond 24 months. Accumulating evidence suggests that two primary fuel sources, sugar (glucose) and glutamine (an amino acid that is a building block of protein) drives the rapid growth of most cancer tumors, including GBM. Waste products from consumption of these fuel sources also contributes to further tumor progression. Hence, the study’s authors believe that the effective management of GBM brain cancer will require restricted availability of the cancer’s fuel sources of glucose and glutamine. To compound the challenge, the current medical approach to battling brain cancer with surgery, radiation and chemotherapy can actually increase the local fuel source of glutamine for the cancer tumor.

This study examined the effect of ketogenic metabolic therapy (KMT) on a patient with glioblastoma multiforme brain cancer. A Ketogenic Diet reduces the sugar fuel needed by the cancer tumor to grow and the diet also elevates ketone bodies as fuel for normal cells, and a fuel that cancer cells cannot easily use for survival. While standard medical treatment is surgical removal of diseased cancer tissue with radiation and chemotherapy, the authors employed a different combination of metabolic therapies: namely diet, radiation, drugs and hyperbaric oxygen therapy with the elimination of steroids. A Ketogenic Diet was chosen to target the ability of cancer cells to convert glucose to energy in presence of air, as KD uses low carbohydrates, thus limiting the use of glucose by tumor cells.

 

Methods

A 38-year-old male patient with no history of cancer malignancy was subsequently diagnosed with Glioblastoma Multiforme (GBM), the most common and malignant of the primary adult brain cancers. The patient had chronic headaches, nausea, vomiting, weakness and seizures.

The patient was put on a restricted Ketogenic Diet with 900 calories per day, with a 4:1 ratio of fats, proteins: carbs which was eaten for 21 days before surgery to remove the tumor. The diet consisted of 71 grams of fat with 639 calories (33% olive/flaxseed oils, 33% medium-chain triglycerides ie. Coconut or MCT oil and 33% organic butter); 50 gram of protein with 200 calories (from eggs, fish and poultry with no more than 15% dairy); and 15 grams of carbs with 60 calories mainly from green leafy vegetables; plus 20 grams of fiber. Supplements were given to maintain nutrients.

Immediately after the surgery, the patient resumed the restricted Ketogenic Diet that also included 14 hours of intermittent fasting between dinner and breakfast each day. Two weeks after the surgery, green tea extract (epigallocatechin gallate) and chloroquine phosphate (an anti-malaria drug) were also given to help stop fuel consumption by the cancer cells. To increase stress on tumor cells, 20 sessions of hyperbaric oxygen therapy was given two weeks after the surgery, in addition to 30 sessions of brain radiation. Hyperbaric oxygen therapy (HBOT) involves exposing the body to 100% oxygen in a high-pressure chamber. Then for nine months the patient was placed a Ketogenic diet of 1,500 calories per day together with Hyperbaric oxygen therapy, radiation and an oral chemotherapy drug, and then followed by a Ketogenic diet only.

 

Results

Twenty-one days after the above diet, tissue examination of patient’s tumor resection craniotomy confirmed GBM. Notable changes were less spread of tumor cells and blood vessels with cartilage – all hallmarks of lower grade tumors, despite no further radiotherapy and chemotherapy given with excellent postoperative recovery. The study attributes this to the Ketogenic Diet before the surgery.

MRI after 3 months of Ketogenic Diet therapy and HBOT, showed no altered tumor size but decreased activity as seen by choline/N-acetylaspartate tests. The third MRI done 9 months later showed a significant reduction in tumor size and metabolism, with decreased BMI to 19.9 from 25.10 during his first presentation.

The fourth MRI done after 3 months of only 1500 kcal/day KD revealed a further decrease in tumor size (1.5 cm) and activity with no edema or midline shift. At the time of publishing, the authors report, “The patient remains in good health with no noticeable clinical or neurological deficits”.

 

Conclusion

The use of ketogenic metabolic therapy before surgery, radiotherapy and chemotherapy with hyperbaric oxygen therapy and lack of steroids caused “favorable therapeutic response” in the brain cancer patient. Lower blood sugar in the patient would reduce fuel in the tumor cells, while the elevation of ketone bodies from the Ketogenic Diet would fuel and protect normal body cells. Generally, the higher the blood sugar, the shorter is the survival from cancer due to faster tumor growth. Studies suggest that lower blood sugar can increase tumor cell death, reduce inflammation and edema in the tumor area thus reducing cancer tumor cell growth and invasion. The authors also believe it is necessary to deprive cancer cells of the fuel glutamine. Hence, the authors used non-toxic green tea extract, EGCG and the anti-malaria drug Chloroquine to attempt to limit glutamine availability to the tumor cells. The authors therefore conclude that a combination of limited availability of glutamine using EGCG and chloroquine along with the Ketogenic Diet metabolic therapy that reduces blood sugar with radiation therapy and chemotherapy, helped the patient’s survival. The author’s state, on a positive note, that “the patient is now 40 years old and remains in excellent health with no noticeable neurological issues (Karnofsky Score, 100%) after 24 months of treatment”. This is compared to less than 20% of younger adults surviving beyond 24 months with brain cancer.

Study Editor

Prerna Pandey holds a Ph.D. in Biotechnology with expertise in Molecular Biology, Microbiology, Virology, and Genomics. She had published several chapters, reviews, and books, and works as a full-time science editor and writer. She can be reached through email: prernapandey@hotmail.com

Citation

Elsakka, A.M.A., Bary, M.A., Abdelzaher, E., Elnaggar, M., Kalamian, M., Mukherjee, P., Seyfried, T.N. (2018). Management of Glioblastoma Multiforme in a Patient Treated with Ketogenic Metabolic Therapy and Modified Standard of Care: A 24-Month Follow-Up. Frontiers in Nutrition. 5:20.