Cancer is a complex disease characterized by the loss of the cellular control over the proliferation, caused by the accumulation of genetic and epigenetic defects. Recent findings shows that one of the major alternations found in almost all cancer cells, is a shift in the cellular glucose metabolism. This phenomenon - high rate glycolysis under aerobic conditions is known as “The Warburg Effect” and it is closely related to high metastatic potential of tumors.
Ketogenic diet is a low carbohydrate diet aim to induce ketosis. At this state, liver is using fatty acids to form acetylo-CoA, which is converted into ketone bodies. Ketone bodies are transported to other tissues where they are reconverted to acetylo-CoA, which can by use directly in Krebs cycle. Many cancer cells lack the activity of succinyl-CoA-acetoacetate-CoA transferase and other enzymes needed in ketone bodies metabolism, thus this source of energy is unavailable for them. KetoCal®, ketogenic diet produced by Nutricia is a nutritionally balanced soybean oil diet that was originally developed for managing refractory epilepsy in children. Recent studies showed that KetoCal®, given in restricted amounts reduces plasma glucose levels and elevates ketone bodies levels leading to significant decrease in the brain tumors growth. Additionally, it showed anti-inflammatory, anti-angiogenic and pro-apoptotic activity.
Our goal was to test the possibility of using ketogenic diet in other kinds of cancers. Moreover, we wanted to check the possible synergistic effects between diet and commonly used cytostatic – cyclophosphamide. In our experiment we used mouse breast cancer model 4T1 that closely resembles breast cancer in humans. Ketogenic diet was administered to Balb/c female mice in restricted amounts (1 gram per day per mouse). KetoCal ® (KD) alone and administered with cyclophosphamide (KD+CY) decreased growth of tumors by about 35% and 80%, respectively, compared to the control group (C) which received standard fodder in unrestricted amounts. Ketogenic diet showed additive effect in inhibiting 4T1 growth when combine with cyclophosphamide. Spleens from group KD+CY were significantly smaller in comparison with the control group. Metastasis in lungs were also significantly lower in KD and KD+CY groups. This results indicate that KetoCal® has anti-tumor and anti-metastatic effect in experimental mouse breast tumors when administered in restricted amounts. We can assume that ketogenic diet can be used in the treatment of the other cancers than brain tumors. Moreover, we showed that it could be use not only as an alternative therapeutic option, but also as an supportive therapy during standard chemothe- rapy.