Ketogenic diet in cancer treatment DR AZADEH NADJARZADEH, PHD IN NUTRITION

Cancer metabolic alteration Rate of glycolytic metabolism even in the presence of oxygen

Ketogenic diet High fat Moderate to low protein Very low carbohydrate

ketogenesis

Clinical application of ketogenic diet Ketogenic diet epilepsyparkinsonalzheimerPCOSautismALS

Ketogenic diet in cancer therapy  1987, Tisdale et al. : decreased tumor weight and improved cachexia in mice with colon adenocarcinoma  Reduce tumor growth and improve survival in animal models of malignant glioma, colon cancer, gastric cancer, gastric cancer, and prostate cancer

 In Cancer increase in cell glucose metabolism as well as alteration in mitochondrial oxidative metabolism  increase mitochondrial DNA mutation  ROS increases  Increased tumor cell ROS increases tumor cell dependence upon glucose metabolism, resulting in generation of NADPH and pyruvate via the pentose phosphate shunt and pyruvate from glycolysis.  NADPH and pyruvate reduce hydroperoxides.

... Redox Biology, Volume 2, 2014, 963–970

 Ketogenic diets decrease the capability of tumor cells to produce NADPH because, in most tissues, fat metabolism is unable to undergo gluconeogenesis to form G6P necessary to enter the pentose phosphate shunt.

 Thus, ketogenic diets should further increase the oxidative stress in tumor cells relative to normal cells by limiting NADPH regeneration.

Ketogenic diet schema Patient recruitment Baseline ketones, Glc, oxidative stress markers Patients begin ketogenic diet 2 days prior to initiating radiochemothe rapy Radiochemothe rapy with concurrent ketogenic diet Daily ketones, Glc, monitor adverse events & weekly oxidative stress markers 30-day follow up Baseline ketones, Glc and oxidative stress markers Follow up every 3 months for 1 year

.. Redox Biology, Volume 2, 2014, 963–970 Possible side effects

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