Case study follows patient with brain cancer on ketogenic diet

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A British man who rejected the standard of care to treat his brain cancer has lived with the typically fatal glioblastoma tumor growing very slowly after adopting a ketogenic diet, providing a case study that researchers say reflects the benefits of using the body's own metabolism to fight this particularly aggressive cancer instead of chemo and radiation therapy. The case study was published recently in in the journal Frontiers in Nutrition.

The report is the first evaluation of the use of ketogenic metabolic therapy (KMT) without chemo or radiation interventions, on a patient diagnosed with IDH1-mutant glioblastoma (GBM). Ketogenic therapy is a non-toxic nutritional approach, viewed as complementary or alternative, that uses a low-carbohydrate, high-fat diet to manage a range of cancers, including glioblastoma.

In this particular case, the patient's tumor contained a mutation, known as the IDH1. This mutation is acquired by chance and is known to improve overall survival. The findings are particularly relevant to other patients whose tumors contain this mutation, according to Thomas Seyfried, PhD, co-author of the report and a professor of biology at Boston College, who said he has long advocated the benefits of KMT to treat disease.

"As GBM, like most malignant cancers, is dependent on fermentation for energy synthesis and survival, the simultaneous restriction of fermentable fuels, such as glucose and glutamine, while elevating non-fermentable ketone bodies, offers a non-toxic therapeutic strategy for managing GBM," said Seyfried in a statement. "Further studies will be needed to test this hypothesis in other patients diagnosed with GBM."

Glioblastoma kills about 15,000 people each year and remains largely unmanageable. While the standard of care has shifted to new immuno-therapies, the median survival time of 11 to 15 months for GBM has not improved significantly for more than 100 years, the authors said.

The current standard of care for GBM involves surgical resection, radiation, and chemotherapy, which have been shown in studies to result in significant toxicity. However, large-scale clinical trials for alternative therapies are difficult to initiate, leading researchers to carefully examine individual cases.

The patient in this case was diagnosed with glioblastoma in 2014 and eschewed the traditional standard of care and instead embarked on a self-directed ketogenic diet, low in carbohydrates and high in fat, to manage his cancer. The researchers found "the patient's tumor continued to grow very slowly over a three-year period without expected vasogenic edema until 2017." 

At that point, the patient underwent "surgical debulking" of his tumor. The pathology specimen confirmed the diagnosis of GBM and that the patient's tumor also contained the IDH1 mutation. "Following surgery, the patient continued with a self-administered ketogenic diet to maintain low Glucose Ketone Index (GKI) values, indicative of therapeutic ketosis," the researchers report. "In light of continued slow progression of the residual tumour, the patient intensified his KMT starting in October, 2018 with inclusion of mindfulness techniques to reduce stress. While Magnetic Resonance Imaging (MRI) shows slow interval tumor progression, the patient remains alive with a good quality of life at the time of this report." He is now at 82 months from original diagnosis.

"We were surprised to discover that KMT could work synergistically with the IDH1 mutation to simultaneously target the two major metabolic pathways needed to drive the growth of GBM," said Seyfried. "Glucose drives the glycolysis pathway, while glutamine drives the glutaminolysis pathway.

Despite the compelling interest in such individual case studies, the co-authors said they cannot predict if the therapeutic response to KMT seen in our GBM patient will also be seen in other similarly treated GBM patients.

“No tumor, including GBM, can survive without glucose and glutamine,” Seyfried said. “Our study has identified a novel mechanism by which an acquired somatic mutation acts synergistically with a low carbohydrate, high fat diet to provide long-term management of a deadly brain tumor.”