Patient on ketogenic therapy completely living with IDH1 mutant glioblastoma: study

A British man who rejected the standard of care for treating his brain tumor lived with the typically fatal glioblastoma tumor that grew very slowly after a ketogenic diet, with particularly aggressive cancers instead of chemotherapy and radiation therapy.

The report, published in the journal Frontiers in Nutrition, is the first to evaluate the use of ketogenic metabolic therapy (BMT) without chemo or radiation intervention in a patient diagnosed with IDH1-mutated glioblastoma (GBM). Ketogenic therapy is a non-toxic nutritional approach considered a supplement or alternative that uses a low-carb, high-fat diet to treat a number of cancers, including glioblastoma.

In this particular case, the patient’s tumor contained a mutation known as IDH1. This mutation is acquired randomly and is known to improve overall survival. Therefore, the results are particularly relevant to other patients whose tumors contain this mutation, according to Thomas Seyfried, professor of biology at Boston College, co-author of the report and a lead researcher who has long advocated the benefits of BMT for treating disease.

“Because GBM, like most malignant cancers, relies on fermentation for energy synthesis and survival, limiting fermentable fuels like glucose and glutamine while increasing non-fermentable ketone bodies offers a non-toxic therapeutic strategy for treating GBM “Said Seyfried.” Further studies are needed to test this hypothesis in other patients diagnosed with GBM.

Glioblastoma kills around 15,000 people each year and remains largely uncontrollable. While the standard of care has shifted to new immunotherapies, the 11 to 15 month median survival time for GBM has not improved significantly in more than 100 years, according to the co-authors.

A number of high profile cases have illustrated the fatal progression of GBM. The late U.S. Senator John McCain was diagnosed with glioblastoma in July 2017 at the age of 80 and died in August 2018. U.S. Senator Edward M. Kennedy lived for a year after being diagnosed with GBM and died at the age of 77. Beau Biden, son of US President Joe Biden, was diagnosed with GBM in August 2013 at the age of 44 and died in May 2015.

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

In this case, the patient was diagnosed with glioblastoma in 2014 and he eschewed traditional standard of care and instead began a self-directed ketogenic diet – low-carb and high-fat – to get his cancer under control.

The researchers found that “the patient’s tumor grew very slowly over a period of three years with no expected vasogenic edema through 2017,” said Seyfried and his co-authors, Boston College researcher Purna Mukherjee, Aditya Shivane, MD, dated University Hospital Plymouth NHS Trust in the UK, U.S. nutritionists Miriam Kalamian, Joseph Maroon, MD, of the University of Pittsburgh, and Giulio Zuccoli, MD, of Drexel University School of Medicine

At this point the patient underwent “surgical debulking” of his tumor. The pathological sample confirmed the diagnosis of GBM and that the patient’s tumor also contained the IDH1 mutation.

“After surgery, the patient continued on a self-administered ketogenic diet to maintain low levels of the glucose ketone index (GKI), which is indicative of therapeutic ketosis,” the researchers report.

“In view of the continued slow progression of the residual tumor, the patient intensified his BMT from October 2018 using mindfulness techniques to reduce stress. While magnetic resonance imaging (MRI) shows slow interval tumor progression, the patient remains with a quality of life at the time of this report. “He is now 82 months away from his original diagnosis.

“We were surprised to discover that KMT can work synergistically with the IDH1 mutation to simultaneously target the two major metabolic pathways required for GBM to grow,” said Seyfried. “Glucose drives the glycolysis pathway while glutamine drives the glutaminolysis pathway.”

He added, “No tumor, including GBM, can survive without glucose and glutamine. Our study identified a new mechanism by which an acquired somatic mutation works synergistically with a low-carbohydrate, high-fat diet for long-term treatment of a deadly brain tumor. “

Despite the compelling interest in such individual case studies, the co-authors state: “We cannot predict whether the therapeutic response to BMT in our GBM patient will also be seen in other similarly treated GBM patients to the spontaneous IDH1 mutation in their tumor glutamine-targeting drugs with BMT will be required to reduce tumor growth. “

The researchers noted that additional studies they conducted showed that targeting glucose and glutamine availability simultaneously using BMT and the pan-glutaminase inhibitor – known as 6-diazo-5-oxo-L- norleucine (DON) – May significantly extend survival in preclinical syngeneic glioblastomas in mice.

Previous research has shown that ketogenic diets can facilitate the delivery of low molecular weight therapeutic drugs across the blood-brain barrier without toxicity.

Related Articles