Normal brain cells can metabolize both glucose and ketone bodies for energy in contrast to brain tumors, which lack metabolic flexibility and are largely dependent on glucose for growth and survival. This study evaluated the efficacy of KetoCal®, a new commercially prepared high fat/low carbohydrate ketogenic diet for children with epilepsy, on the growth and vascularity of a mouse astrocytoma (CT-2A) and a human glioma (U87-MG). KetoCal® was administered to adult mice in restricted amounts to reduce body weight by approximately 20%. KetoCal® significantly decreased the intracerebral growth of the CT-2A and U87-MG tumors by about 65% and 35%, respectively, and significantly enhanced health and survival relative to that of the control group receiving a standard low fat/high carbohydrate diet. The KetoCal® diet reduced plasma glucose levels while elevating plasma ketone body (b-hydroxybutyrate) levels. Tumor microvessel density was less in the restricted KetoCal® group than in the control group. Moreover, gene expression for b-hydroxybutyrate dehydrogenase and succinyl-CoA: 3-ketoacid CoA transferase, key enzymes for ketone body metabolism, was lower in the tumors than in the contra lateral normal brain, suggesting that these brain tumors have reduced ability to metabolize ketone bodies for energy. These results indicate that KetoCal® has anti-tumor and antiangiogenic effects in experimental mouse and human brain tumors and should be clinically effective for managing malignant brain cancer in humans.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA