The Ketogenic Diet

Could a ketogenic diet for cancer prove beneficial? In this case study, a British man rejected the standard of care to treat his terminal brain cancer. After adopting a ketogenic diet in 2014, his typically fatal glioblastoma tumour grew at a very slow rate.

As the study notes, successful treatment of glioblastoma (GBM) continues to elude, despite decades of intense research.

It is known that GBM is similar to most other malignant cancers in that is needs glucose and glutamine for growth, regardless of histological or genetic heterogeneity. A ketogenic metabolic therapy (KMT) is a nutritional intervention for cancer management that this 32-year-old man employed after he experienced seizures and a right frontal lobe tumour on MRI.

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. So the findings are particularly relevant to other patients whose tumours contain this mutation.

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

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

The researchers found “the patient’s tumour continued to grow very slowly over a three-year period without expected vasogenic edema until 2017,” according to Seyfried and his co-authors, Boston College researcher Purna Mukherjee, Aditya Shivane, MD, of University Hospital Plymouth NHS Trust, in the United Kingdom, U.S.-based nutritionist Miriam Kalamian, Joseph Maroon, MD, of the University of Pittsburgh, and Giulio Zuccoli, MD, of the Drexel University School of Medicine

At that point, the patient underwent “surgical debulking” of his tumour. The pathology specimen confirmed the diagnosis of GBM and that the patient’s tumour 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 tumour 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

The researchers noted that additional studies they’ve conducted have shown that the simultaneous targeting of glucose and glutamine availability, using KMT and the a pan-glutaminase inhibitor – known as 6-diazo-5-oxo-L-norleucine (DON) – can significantly prolong survival in preclinical syngeneic glioblastomas in mice. Earlier research has shown that ketogenic diets can facilitate delivery of small-molecule therapeutic drugs through the blood brain barrier without toxicity.

Reference

Seyfried Thomas N., Shivane Aditya G., Kalamian Miriam, Maroon Joseph C., Mukherjee Purna, Zuccoli Giulio. Ketogenic Metabolic Therapy, Without Chemo or Radiation, for the Long-Term Management of IDH1-Mutant Glioblastoma: An 80-Month Follow-Up Case Report, Frontiers in Nutrition , Vol 8; 2021. doi:10.3389/fnut.2021.682243