From antiepileptic therapy to promising adjuvant in medical oncology: A historical view of the ketogenic diet

Background: Despite recent advances that have been made in cancer treatment, we still lack complementary approaches to significantly improve the effectiveness of current anti-cancer therapies. The high-fat, low-carbohydrate ketogenic diet can cause metabolic changes in the tumor microenvironment, thus targeting cancer metabolism, making it an attractive candidate for adjuvant cancer therapy. This review is an attempt to explore the origin and trace the historical use of the ketogenic diet as a metabolic therapy in medical oncology. Methods: A detailed literature review was conducted through specialized databases. Only those articles pertinent to the specific needs of the review were included. Relevant references in those articles were also followed. Results: There is a sound biological rationale for the anti-tumor force of the ketogenic diet primarily manifested through its anti-Warburg effect. It is no less true that Otto Warburg's experiments have based the ketogenic diet in cancer research on solid footing. However, precisely tracing the initial, original anti-tumor use of the ketogenic diet in medical oncology literature has indeed proved to be a hard needle to thread. The currently available data are considered promising in the pre-clinical rodent models. Yet, the number of rigorous human trials is small and suffers from methodological limitations. Conclusions: Further research, both pre-clinical and clinical, is needed to accurately define the anti-tumor effect of the ketogenic diet and to overcome the current methodological limitations that hinder us from deriving a sound judgment about the use of the ketogenic diet in clinical practice.