Epilepsy Diet is Effective in Managing Malignant Brain Cancer
6 Mar, 2007 10:35 am
The ketogenic diet is a high fat, low carbohydrate and low protein diet that has been used for decades as a last resort for managing drug-resistant seizures in children with epilepsy. Our study, published in the online journal Nutrition and Metabolism, showed that a new ketogenic diet (KD) for children with epilepsy is also effective for managing malignant brain tumor growth in mice.
The metabolism of ketone bodies requires functional mitochondria, small organelles inside cells that produce most of the cell’s energy. Ketone body metabolism is an evolutionarily conserved process that spares protein breakdown so that the brain can function for long periods without food. The human brain is especially adept at making the metabolic transition from glucose to ketone bodies for energy, as this adaptation has been responsible in part for the evolutionary success of our species on this planet.
In contrast to normal brain cells, which can metabolize either glucose or ketone bodies for energy, most tumors including brain tumors lack metabolic flexibility and are largely dependent on glucose for energy. The German biochemist, Otto Warburg, first found that most energy in tumor cells is produced through glycolysis, a primitive and inefficient form of glucose-dependent energy metabolism. Moreover, Warburg showed that the glycolytic dependence of tumor cells was due to defects in their mitochondria. In other words, the main energy power plant of tumor cells is defective thus forcing the tumor cells to rely on glucose and glycolysis for energy. These defects in energy metabolism make tumor cells vulnerable to elimination through principles of evolutionary biology and metabolic control theory.
Our study evaluated the efficacy of KetoCal®, a new commercially prepared and nutritionally balanced KD for children with epilepsy, on the growth of experimental mouse and human malignant brain tumors. The malignant brain tumors were implanted into the brains of adult mice and KetoCal® was administered in either unrestricted amounts or in restricted amounts to reduce total caloric intake according to the manufacturers recommendation for children with refractory epilepsy. The effects KetoCal® on tumor growth, vascularity, and mouse survival were compared with that of an unrestricted high carbohydrate standard diet.
The results showed that the KetoCal® significantly decreased the growth of the brain tumors and significantly enhanced health and survival relative to that of the control groups receiving a standard low fat/high carbohydrate diet. Most importantly, these effects were observed only when the diet was administered in calorically restricted amounts, but were not observed when administered in unrestricted amounts indicating, that “less is best”. The restricted KD is effective in managing brain tumors because it lowers circulating glucose levels, which the brain tumor cells need for survival, while elevating ketone bodies, which become the main energy source for normal cells when glucose is limited.
Tumor blood vessel density (angiogenesis) was also less in the calorically restricted KetoCal® groups than in the calorically unrestricted control groups indicating that the diet reduces tumor blood vessels, which bring food to the tumor cells. Moreover, analysis of gene activity suggested these brain tumors have reduced ability to metabolize ketone bodies for energy, findings consistent with past studies in other tumors. The diet acts to metabolically isolate and starve the tumor cells. Our work in mice also supports previous findings from Dr. Linda Nebeling and co-workers who showed that a KD was effective in managing inoperable brain cancer in children. Hence, our findings in mice relate directly to previous findings in humans.
The world-wide incidence of malignant brain tumors is increasing in both children and the elderly. Despite these ominous findings, the standard therapies for malignant gliomas are basically the same today as they have been for over five decades (surgical resection and radiation). While these therapies may retard glioma growth over the short term, they may actually facilitate tumor recurrence over the longer term. Chemotherapy has little long-term benefit on most malignant gliomas and is often associated with unacceptable adverse effects that diminish the length or quality of life. The therapeutic targeting of brain tumor-associated mutations is also problematic as most tumor mutations arise as secondary consequences of tissue disorganization and are not expressed in all cells of the tumor.
In contrast to most conventional brain tumor therapies, which indiscriminately target both tumor cells and normal cells, caloric restriction and particularly restricted KDs are the only known therapies that can target brain tumor cells while enhancing the health and vitality of normal brain cells. In this regard, the calorically restricted KD for brain cancer management stands apart from all major conventional therapeutic approaches. If used initially upon diagnosis of malignant brain cancer, the diet could eliminate the need for harmful radiation therapy, could reduce exposure to toxic chemotherapy, and could facilitate a more complete surgical removal of tumor tissue.
Reference: Zhou W, Mukherjee P, Kiebish MA, Markis WT, Mantis JG, and Seyfried TN. The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer. Nutr Metab (Lond). 2007 Feb 21;4:5