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Ketogenic diet in cancer therapy

Daniela D. Weber,Sepideh Aminazdeh-Gohari,B. Kofler

Published 2018 in Aging

ABSTRACT

The Ketogenic Diet (KD), a high-fat/low-carbohydrate/ adequate-protein diet, has recently been proposed as an adjuvant therapy in cancer treatment [1]. KDs target the Warburg effect, a biochemical phenomenon in which cancer cells predominantly utilize glycolysis instead of oxidative phosphorylation to produce ATP. Furthermore, some cancers lack the ability to metabolize ketone bodies, due to mitochondrial dysfunction and down-regulation of enzymes necessary for ketone utilization [2]. Thus, the rationale in providing a fatrich, low-carbohydrate diet 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. Numerous preclinical studies have provided evidence for an anti-tumor effect of KDs [1] (Figure 1). For example, our laboratory intensively studied the antitumor effect of KDs in combination with or without low-dose chemotherapy on neuroblastoma. We found that the growth of neuroblastoma xenografts was significantly reduced by a KD consisting of a 2:1 ratio of fat to carbohydrate + protein when combined with caloric restriction [2]. However, caloric restriction, despite its anti-tumor effect and potential to sensitize cancer cells to chemotherapy, would be contraindicated in a range of cancer patients, particularly those with cachexia. Thus, we further focused on optimizing the KD composition to address this issue. We found that an ad libitum KD (8:1) with a fat content of 25% mediumchain triglycerides and 75% long-chain triglycerides produced a stronger anti-tumor effect compared to a KD (8:1) with all long-chain triglycerides, and was as efficacious against neuroblastoma as the abovedescribed KD (2:1) combined with caloric restriction [3]. These results stress the importance of an optimized KD composition to suppress tumor growth and to sensitize tumors to chemotherapy without requiring caloric restriction. In addition to neuroblastoma, various researchers have investigated the efficacy of KDs as an adjuvant therapy for other types of cancer. The strongest evidence (> 3 studies) for a tumor-suppressing effect has been reported Editorial

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