Ketogenic diets as an adjuvant cancer therapy: History and potential mechanism

Abstract

Cancer cells, relative to normal cells, demonstrate significant alterations in metabolism that are proposed to result in increased steady-state levels of mitochondrial-derived reactive oxygen species (ROS) such as O2•−and H2O2. It has also been proposed that cancer cells increase glucose and hydroperoxide metabolism to compensate for increased levels of ROS. Given this theoretical construct, it is reasonable to propose that forcing cancer cells to use mitochondrial oxidative metabolism by feeding ketogenic diets that are high in fats and low in glucose and other carbohydrates, would selectively cause metabolic oxidative stress in cancer versus normal cells. Increased metabolic oxidative stress in cancer cells would in turn be predicted to selectively sensitize cancer cells to conventional radiation and chemotherapies. This review summarizes the evidence supporting the hypothesis that ketogenic diets may be safely used as an adjuvant therapy to conventional radiation and chemotherapies and discusses the proposed mechanisms by which ketogenic diets may enhance cancer cell therapeutic responses.

Buffered vs. Non-Buffered Aliphatic Fatty Acids and their Anti-Proliferative Effects in Human Tumor Cell Lines

“…In a direct human application, a high ketogenic diet would theoretically force these cells to use the very oxidative metabolism they are trying to offset. Hence fat exposure in and of itself (as an energy source) is expected to be anti-neoplastic in nature for several reasons [39].…”

Optimal Control Analysis of a Mathematical Model for Breast Cancer

“…[5]. Surgery, chemotherapy, radiation therapy, hormonal therapy, hyperthermia, targeted therapy and ketogenic diet [5,6] amongst other therapeutics are used to inhibit tumor growth or kill the tumor cells in the body. However, each treatment has side effects attributed to it, for example, hair loss, vomiting, nausea and fatigue.…”

“…Until recently, a few studies, such as [6][7][8], investigated diet as a possible adjuvant to cancer treatment, which includes a ketogenic diet. A ketogenic diet consists of high edible fat with moderate or low protein content and very low carbohydrates, which forces the body to burn fat instead of glucose for adenosine triphosphate (ATP) synthesis [6,9].…”

Patient Preparation for Oncological FDG-PET/CT Imaging

“…CT component of the system provides attenuation correction and allows imaging of anatomical structures with a geometric resolution higher than the PET component [5]. The diagnostic value of FDG-PET/CT is based on the fact that most cancers demonstrate increased glucose consumption compared to normal cells [6]. Discrimination of benign and malignant tumours, detection of unknown primary tumors in patients presenting with metastases, staging of cancer patients, imaging of tumour recurrences and monitorization of tumour response to therapy are among the major indications of oncological FDG-PET/CT imaging (scanning) [4, 7−13].…”