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Prevention Research 7: Diet and Diet-related Factors

Abstract #3887

KetoCal®, a novel ketogenic diet therapy for brain cancer

Boston College, Chestnut Hill, MA

The ketogenic diet (KD) is a high fat/low carbohydrate diet that has been used for decades to manage epileptic seizures in children. Our recent findings suggest that the bioenergetic transition from glucose to ketone bodies will metabolically target brain tumors through integrated anti-inflammatory, anti-angiogenic, and pro-apoptotic mechanisms. This study evaluated the efficacy of KetoCal®, a new specially formulated commercial ketogenic diet for children, on the growth and angiogenic properties of a mouse astrocytoma (CT-2A) and a human glioma (U87-MG) that were orthotopically implanted in C57BL/6J and BALBc/J (SCID) mice, respectively. KetoCal®was administered to the mice in a restricted amount to maintain body weight at approximately 80% of the standard (high carbohydrate) chow-fed control group. Circulating glucose and ketone body levels were monitored as measures of energy consumption. Protein and gene expressions for succinyl-CoA-acetoacetate-CoA transferase (SCOT) and betahydroxybutyrate dehydrogenase (ß-OHBDH), key enzymes for ketone metabolism, were investigated in tumors and contra-lateral normal brain tissue. The tumors were analyzed for microvessel density (Factor VIII) as a marker for tumor angiogenesis. KetoCal® significantly decreased the intracerebral CT-2A and U87-MG growth by about 70% and 35%, respectively, and significantly enhanced survival relative to the control groups. The diet significantly reduced blood glucose while elevated ß-hydroxybutyrate dehydrogenase levels. SCOT and ß-OHBDH expressions were significantly lower in the tumors than in the brain suggesting that the brain tumor cells have impaired ability to metabolize ketone bodies for energy. Microvessel density was significantly lower in the KetoCal® groups than in the control groups. These results indicate that KetoCal® has anti-tumor and anti-angiogenic effects in experimental mouse and human brain tumors, and should have clinical efficacy for managing malignant human brain cancer. Supported by the National Institutes of Health grants (HD39722) and (CA102135), and a grant from the American Institute of Cancer Research.