The Ketogenic Diet (KD), a high-fat/low-carbohydrate/adequate-protein diet, has recently been proposed as an adjuvant therapy in cancer treatment. KDs target the Warburg effect, a biochemical phenomenon in which cancer cells predominantly utilize glycolysis instead of oxidative phosphorylation to produce A TP . Furthermore, some cancers lack the ability to metabolize ketone bodies, due to mitochondrial dysfunction and down-regulation of enzymes necessary for ketone utilization. Thus, the rationale in providing a KD in cancer therapy is to reduce circulating glucose levels and induce ketosis such that cancer cells are starved of energy while normal cells adapt their metabolism to use ketone bodies and survive. Furthermore, by reducing blood glucose also levels of insulin and insulin-like growth factor, which are important drivers of cancer cell proliferation, drop.

Evidence that ketogenic diet in cancer patients is safe and feasible as an adjuvant therapy, if carefully monitored.

In order to see any significant improvement, at least 3 to 4 weeks of ketogenic diet is required.

Importance of an optimized KD composition to suppress tumor growth and to sensitize tumors to chemotherapy without requiring caloric restriction (fat content of 25% medium-chain triglycerides and 75% long-chain triglycerides produced a stronger anti-tumor effect compared to a KD (8:1) with all long-chain triglycerides).

Most concerning is the observation that, in a mouse model of BRAF V600E-positive melanoma, tumor growth was significantly increased under the KD : the ketone body acetoacetate stimulated the oncogenic signaling of the BRAF pathway.

The strongest evidence for a tumor-suppressing effect has been reported for glioblastoma, whereas little or no benefit was found for two other brain tumors (astrocytoma and medullo-blastoma). Good evidence is available for prostate, colon, pancreatic, lung cancer and neuroblastoma.

=> Clinical application of KDs as an adjuvant therapy for cancer patients first requires that the KD be evaluated for its anti-tumor effect for each single type/genetic subtype of cancer in a preclinical setting, as the safety and efficacy of the KD strongly depend on the tumor entity and its genotype.