Our results demonstrate that KC, when administered ad libitum, enhances survival and slows tumor growth in our mouse model of brain tumors. KC potentiates the effect of radiation by extending survival beyond that seen with radiation alone. Irradiated animals Abmole XVA 939 maintained on KC demonstrated a complete loss of tumor-based bioluminescence, suggesting tumor regression and the absence of viable tumor cells. Tumors in this cohort of animals did not recur when animals were put back on standard rodent chow. The effectiveness of the ketogenic diet as an alternative treatment for malignant glioma was first reported by Seyfried et al based on the idea that while normal brain can effectively use Abmole FK506 ketones as an energy source, tumor cells cannot. Using the syngeneic CT-2A and the xenograft U87 brain tumor models, Zhou et al showed that caloric restriction sufficient to cause a drop in blood glucose also significantly increased survival. Furthermore, when the ketogenic diet was given in restricted amounts this effect was more pronounced. In contrast, when the ketogenic diet or standard rodent chow was given ad libitum they did not find a drop in blood glucose nor did they see a significant change in survival. Recently, Maurer et al used long-term human glioma cell lines and rat hippocampal neurons to analyze their utilization of ketone bodies in vitro. They showed that although the enzymes required to metabolize ketones are present in these glioma cells, the addition of 3-hydroxybutyrate to the culture media did not protect the cells from glucose deprivationinduced cell death, nor did it alter the cells’proliferation, migration or invasive properties. They also found that a ketogenic diet did not alter tumor growth or extend the life of mice given an orthotopic injection of LNT-229 glioma cells when compared to mice maintained on standard diet. This is in contrast to our previous work using a rodent ketogenic diet and the work described in this manuscript in which a human ketogenic formulation was used. The reason for this is unclear, but may have to do with differences in the diet formulations. Maurer et al used a diet with a ratio of fats to carbohydrates and protein of 2.7:1. The rodent diet we used had a 6:1 ratio and KC has a 4:1 ratio. Furthermore, there are a number of papers in the literature demonstrating that ketones have proapoptotic and chemoattractant activity, in contrast to the results reported by Mauer et al. Thus, the response to ketones may be related, in part, to the cell line and/or model system used. Our investigation demonstrates a significant reduction of blood glucose levels between SD and KC fed ad libitum.