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Some of the most exciting research regarding the ketogenic diet has been in its use against cancer. This research is showing that a high-fat low-carbohydrate diet can starve cancer cells. We published several stories on the ketogenic diet and cancer in 2013.
In this study conducted at the University of Pittsburgh Medical Center, the ketogenic diet was used successfully to treat brain tumors.
The Restricted Ketogenic Diet: An Alternative Treatment Strategy for Glioblastoma Multiforme
a report by Thomas N. Seyfried, Purna Mukherjee, Miriam Kalamian and Giulio Zuccoli
Biology Department, Boston College; Dietary Therapies, LLC, Hamilton; Radiology Department University of Pittsburgh Medical Center, Children’s Hospital of Pittsburgh, Pittsburgh
Glioblastoma multiforme (GBM) is considered the most malignant of primary brain cancers with only about 12% of patients living beyond 36 months (long-term survivors).
Ketogenic Diet and Calorie Restriction
The high fat, low carbohydrate ketogenic diet (KD) has long been recognized as an effective non-toxic therapy for reducing epileptic seizures in children. The mechanisms by which the KD manages seizures are linked to shifts in brain energy metabolism. Glucose is the sole metabolic fuel used for nearly all brain functions under normal physiological conditions, but the brain will metabolize ketone bodies for energy when access to glucose is limited, as would occur during water-only therapeutic fasting in humans or during calorie restriction in mice. It has long been known that water-only fasting or calorie restriction is effective in managing epilepsy in humans and mice.
The KD was introduced as an alternative to fasting for the long-term management of seizures in humans. The efficacy of the classic KD is optimal when the ratio of dietary fats to combined carbohydrate/protein is 4:1. This requires careful attention to diet calculations. Importantly, the KD is also gaining recognition as a potential therapy for a host of other neurological and neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, traumatic brain injury, and stroke. When administered in restricted amounts, which do not exceed the individual’s total energy needs, the KD can also be therapeutic against malignant brain tumors in mice and humans.
Evidence from Case Reports
In 1995, Nebeling and coworkers attempted the first nutritional metabolic therapy for human malignant brain cancer using the ketogenic diet. The objective of the study was to shift the prime substrate for energy metabolism from glucose to ketone bodies in order to disrupt tumor metabolism while maintaining the nutritional status of patients. The patients in this landmark clinical study included two female children with nonresectable advanced stage brain tumors (anaplastic astrocytoma stage IV, and cerebellar astrocytoma stage III). Measurable tumor remained in both subjects following extensive radiation and chemotherapy. Although severe life threatening adverse effects occurred from the radiation and chemotherapy, both children responded remarkably well to the KD and experienced long-term tumor management without further chemo or radiation therapy. Indeed, one of the patients remains alive at the time of this writing (Nebeling, personal communication). Positron Emission Tomography with fluro-deoxy-glucose (FDG-PET) also showed a 21.8% reduction in glucose uptake at the tumor site in both subjects on the KD. These findings indicate that a ketogenic diet, which lowers glucose and elevates ketone bodies, could reduce glycolytic energy metabolism in these brain tumors.
Despite the documented efficacy of the RKD as a non-toxic metabolic therapy for brain cancer in case reports, no major clinical trials of this therapy have been initiated in the US to date. A clinical trial using the unrestricted KD for recurrent glioblastoma has been initiated in Germany (ERGO Trial) under the direction of J. Rieger at the University of Tübingen. Modest improvement was reported without adverse effects, but no published information is yet available on blood glucose or blood ketone levels in the treated patients. This information will be needed to gauge the degree of energy stress on surviving tumor cells, as blood glucose levels are predictive of therapeutic efficacy. Careful documentation of blood glucose and ketone levels will be essential for predicting therapeutic efficacy.
The reason for not initiating clinical trials on the RKD for brain cancer management in the US remains unclear. Some have suggested that the North America Brain Tumor Collaborative (NABTC) prefers “hand-medown” drug therapies from other cancer studies rather than exploring potentially more effective alternative approaches. It is unknown if the reluctance to consider alternative approaches to GBM management rests with the NABTC or with those who advise the Collaborative. Based on pre-clinical studies in mice and case studies in patients, it is obvious that the RKD should be investigated for its therapeutic potential for managing GBM and other malignant brain cancers. The failure to initiate clinical trials is unfortunate especially for those GBM patients who might benefit from using the RKD for managing their disease.
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