KETOGENIC DIETS IN BREAST AND GYNECOLOGIC CANCERS PATIENTS - The Worls Congress of Surgery, ISW 2022

Introduction Because obesity is correlated with detrimental impacts on breast and gynecologic cancers risk, on treatment side effects and on cancer-specific and all-cause mortality, the recommendation before and after diagnosis is to attain and maintain a healthy body weight. Are ketogenic diets efficient and safe in this patient population? Materials & Methods The current scientific literature review on ketogenic diets performed in oncology settings – either clinical or preclinical studies – shows that here are 4 basic things one should know when considering ketogenic diet (KD) in oncology settings. Results First, there are two types of low carb diets: high protein and high fat. KD are high fat diets with a protein intake lower than the one recommended in oncology settings. Second, oncology nutrition is not weight loss nutrition, but clinical supportive care helpful on a day-to-day basis unlike the general population, cancer patients experience: on one side - mucositis, diarrhea, constipation, bloating, dysphagia and nausea - influencing their ability to digest many foods and on the other side - fatigue, disturbed sleep, and emotional distress - influencing their ability to control their eating behavior Although many of the available studies simply label low carb diets as “ketogenic” and people with all sorts of tumors as “cancer patients”, efficient oncology nutrition is as personalized as the many individual cancers and their treatments. And even obesity impact is different in different cancer populations. For instance, obesity impact is different in breast vs gynecologic cancer patients, and so should be these people’s oncology nutrition. Third, there is no evidence for long-term maintenance of the initial weight loss. Most available data come from neurology – showing that only 3/10 adults still follow KD at 12 months. The price for the impressive short-term efficacy is yo-yo dieting, constipation, nausea, and nutrient deficiencies. And fourth, there is no evidence of anti-tumor effects, simplistic hypothesis that negates cancer metabolism complexity. Even in cells whose mitochondria don’t work that well, ketones promote de novo mitochondria biogenesis. There are few KD clinical studies performed specifically with breast and gynecologic cancers patients, KD data in oncology settings consisting on case reports and preclinical data. And preclinical data shows that cancers are heterogenous, having many metabolic pathways to use besides aerobic glycolysis. Many cancers can use fatty acids to resist treatment and support proliferation, and some of the cancers with high metabolic plasticity are the HER2+ breast cancers and the high-grade ovarian serous cancer. Conclusion Breast and gynecologic cancers patients don’t have to lose weight for the sake of weight loss, to improve their prognosis they must lose fat without losing muscle and this is harder to maintain long-term with KD. Also, based on the high metabolic plasticity, no food, diet or dietary supplement can treat cancer. So, please mind the gap between popular short-term fast weight loss nutrition and the clinical oncology nutrition. References Alfarouk, Khalid O., et al. "Evolution of tumor metabolism might reflect carcinogenesis as a reverse evolution process (dismantling of multicellularity)." Cancers 3.3 (2011): 3002-3017. Braicu, Elena Ioana, et al. "High-grade ovarian serous carcinoma patients exhibit profound alterations in lipid metabolism." Oncotarget 8.61 (2017): 102912. Bergqvist, AG Christina. "Long-term monitoring of the ketogenic diet: Do's and Don’ts." Epilepsy research 100.3 (2012): 261-266. Hall, Kevin D., and Juen Guo. "Obesity energetics: body weight regulation and the effects of diet composition." Gastroenterology 152.7 (2017): 1718-1727. Miller, Vincent J., Frederick A. Villamena, and Jeff S. Volek. "Nutritional ketosis and mitohormesis: potential implications for mitochondrial function and human health." Journal of nutrition and metabolism 2018 (2018). R mer, Maximilian, Jennifer D rfler, and Jutta Huebner. "The use of ketogenic diets in cancer patients: a systematic review." Clinical and experimental medicine 21.4 (2021): 501-536. Schmidt, Melanie, et al. "Effects of a ketogenic diet on the quality of life in 16 patients with advanced cancer: A pilot trial." Nutrition & metabolism 8.1 (2011): 1-13. Wang, Lingling, Shizhen Zhang, and Xiaochen Wang. "The metabolic mechanisms of breast cancer metastasis." Frontiers in Oncology 10 (2021): 2942. Weber, Daniela D., et al. "Ketogenic diet in the treatment of cancer–where do we stand?" Molecular metabolism 33 (2020): 102-121. Ye, Fang, et al. "Efficacy of and patient compliance with a ketogenic diet in adults with intractable epilepsy: a metaanalysis." Journal of Clinical Neurology 11.1 (2015): 26-31.