Mitochondria: The ketogenic diet-A metabolism-based therapy.
"The ketogenic diet is used therapeutically for pharmacoresistant epilepsy and for "rare diseases" of glucose metabolism (glucose transporter type 1 and pyruvate dehydrogenase deficiency). As metabolic reprogramming from oxidative phosphorylation toward increased glycolysis is a hallmark of cancer cells; there is increasing evidence that the ketogenic diet may also be beneficial as an adjuvant cancer therapy by potentiating the antitumor effect of chemotherapy and radiation treatment"
Ketogenic diets as an adjuvant cancer therapy: History and potential mechanism.
"Cancer cells, relative to normal cells, demonstrate significant alterations in metabolism that are proposed to result in increased steady-state levels of mitochondrial-derived reactive oxygen species (ROS) such as O2•-and H2O2. It has also been proposed that cancer cells increase glucose and hydroperoxide metabolism to compensate for increased levels of ROS. Given this theoretical construct, it is reasonable to propose that forcing cancer cells to use mitochondrial oxidative metabolism by feeding ketogenic diets that are high in fats and low in glucose and other carbohydrates, would selectively cause metabolic oxidative stress in cancer versus normal cells. Increased metabolic oxidative stress in cancer cells would in turn be predicted to selectively sensitize cancer cells to conventional radiation and chemotherapies."
Metabolic reprogramming induced by ketone bodies diminishes pancreatic cancer cachexia
"A ketogenic diet, a high-fat and low-carbohydrate diet that elevates circulating levels of ketone bodies (i.e., acetoacetate, β-hydroxybutyrate, and acetone), serves as an alternative energy source. It has also been proposed that a ketogenic diet leads to systemic metabolic changes. Keeping in view the significant role of metabolic alterations in cancer, we hypothesized that a ketogenic diet may diminish glycolytic flux in tumor cells to alleviate cachexia syndrome and, hence, may provide an efficient therapeutic strategy"
Full Text: Shukla SK, Gebregiworgis T, Purohit V, et al. Metabolic reprogramming induced by ketone bodies diminishes pancreatic cancer cachexia. Cancer & Metabolism. 2014;2:18. doi:10.1186/2049-3002-2-18.
A Low Carbohydrate, High Protein Diet Slows Tumor Growth and Prevents Cancer Initiation
"Moreover, whereas only 1 mouse on the Western diet achieved a normal life span, due to cancer-associated deaths, more than 50% of the mice on the low CHO diet reached or exceeded the normal life span. Taken together, our findings offer a compelling preclinical illustration of the ability of a low CHO diet in not only restricting weight gain but also cancer development and progression."
Full Text: Victor W. Ho et al, A Low Carbohydrate, High Protein Diet Slows Tumor Growth and Prevents Cancer Initiation. Cancer Res July 1, 2011 71:4484-4493; Published OnlineFirst June 14, 2011; doi:10.1158/0008-5472.CAN-10-3973
Acetoacetate reduces growth and ATP concentration in cancer cell lines which over-express uncoupling protein 2
"Seven human cancer cell lines grown in glucose plus acetoacetate medium showed tightly coupled reduction of growth and ATP concentration. The findings were not observed in control fibroblasts. The observed over-expression of UCP2 in cancer lines, but not in controls, provides a plausible molecular mechanism by which acetoacetate spares normal cells but suppresses growth in cancer lines. The results bear on the hypothesized potential for ketogenic diets as therapeutic strategies."
The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer
"We found that KetoCal®, a nutritionally balanced and commercially available ketogenic diet for children with epilepsy, significantly reduced the orthotopic growth and the vascularity of the mouse astrocytoma (CT-2A) and the human glioma (U87). Moreover, KetoCal® significantly prolonged survival in the tumor-bearing mice. It is important to mention that the anti-angiogenic and growth inhibitory effects of KetoCal® were observed only when the diet was administered in restricted amounts but were not seen when the diet was administered ad libitum, or in unrestricted amounts."
Targeting energy metabolism in brain cancer: review and hypothesis
"In contrast to malignant brain tumors that are largely dependent on glycolysis for energy, normal neurons and glia readily transition to ketone bodies (ß-hydroxybutyrate) for energy in vivo when glucose levels are reduced. The bioenergetic transition from glucose to ketone bodies metabolically targets brain tumors through integrated anti-inflammatory, anti-angiogenic, and pro-apoptotic mechanisms. The approach focuses more on the genomic flexibility of normal cells than on the genomic defects of tumor cells and is supported from recent studies in orthotopic mouse brain tumor models and in human pediatric astrocytoma treated with dietary energy restriction and the ketogenic diet."
Effects of a ketogenic diet on tumor metabolism and nutritional status in pediatric oncology patients: two case reports
"Within 7 days of initiating the ketogenic diet, blood glucose levels declined to low-normal levels and blood ketones were elevated twenty to thirty fold. Results of PET scans indicated a 21.8% average decrease in glucose uptake at the tumor site in both subjects. One patient exhibited significant clinical improvements in mood and new skill development during the study. She continued the ketogenic diet for an additional twelve months, remaining free of disease progression."
Effect of insulin on weight loss and tumour growth in a cachexia model.
"These results suggest that a ketogenic diet is more effective than insulin administration in reversing the cachectic process and has the advantage of a concomitant reduction in tumour weight."