The ketogenic diet and its effect on cancer patients

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1 The ketogenic diet and its effect on cancer patients EMPACTS organic chem Spring Semester 2018 w/ Dr. Chun By: Jordan Kennedy, Bowan Fedosky, Shyann Graham, Josh Whittington

2 Introduction Ketogenic diet has many touted benefits; weight loss, lowering cholesterol, reversing diabetes, possible cancer benefits Project will consist of research in peer reviewed literature, implementation of diet by group members, a survey of medical professionals and their opinions on the diet. Importance of the project is to corroborate emerging research in the arena of cancer treatment via alternate means. Background research conducted via NWACC library database consisting of four studies chosen for applicability to project goals.

3 Project Overview Project was intended to explore and demonstrate the efficacy of using the ketogenic diet in treating cancer. Goal was achieved through review of current research on topic, implementation of ketogenic diet by group members and a survey of medical professionals on their experiences and opinions of using diet as a form of treatment for cancer. Project benchmarks Research: All members via article summary assignment Diet implementation: Kennedy, Fedosky, Whittington Powerpoint and Graphics: All members Survey and assoc. graphics: Kennedy Written Report: All members

4 Community Aspect Jordan Kennedy created and disseminated a survey to medical professionals at Washington Regional Medical Center to gauge their opinions on the concept of treating cancer with diet. Results were an overwhelming lack of support for this as being a beneficial course of treatment. Future community evolvement could be centered around developing research on human subjects, exhibiting the efficacy of diet research in treating disease.

5 Course Content Objectives Determine a clinical definition of metabolic ketosis. Determine what medical studies have found, in regard to cancer response to ketone metabolism Undergo trial diet and record results to test efficacy Distribute survey to medical professionals and gauge opinion on topic. Articulate physiological difference between normal metabolism and ketone metabolism.

6 Methods and Technology Methods Research was conducted using NWACC database for clinical research pertaining to keto diet and cancer Diet implemented by group members with ongoing monitoring to test efficacy. Survey given to medical professionals to gauge opinion on topic. Technology Slide show created using Mac Keynote program Diet monitoring conducted via ReliOn Blood Glucose meter, Bayer Ketone urine test strips, Home-med digital scale. NWACC library search engine for professional literature.

7 Technology Laboratory: Glucose Meter: ReliOn Prime Model Test Strips: Bayer Ketostix/ Siemens Multistix 10-SG. Scale: Health-o-Meter digital scale Model HDR743DQ-41 Project: Google Drive Microsoft Office Excel, Word, Google Slides, Keynote (Mac), Internet

8 Clinical Definition of Ketosis Ketosis is achieved when the body begins to burn ketone bodies as opposed to glucose. Ketones are able to enter the body s metabolism at Krebs cycle or TCA cycle, effectively bypassing the mechanism for processing glucose. In many ways ketosis is much more efficient than normal carbohydrate metabolism

9 Glycolysis This is the process of glycolysis, ketone bodies will skip this and enter the metabolism just below the level of pyruvate.

12 Glucose/Glutamine deprivation When glucose stops coming in the body has a physiological response. Glucagon levels rise, Insulin levels drop, and Fatty Acid oxidation begins The result of this process is a drastic increase of Acetyl-CoA levels. Since Acetyl-CoA cannot revert back to Pyruvate, the body begins to convert it for fuel in the place of Glucose. The Citric Acid Cycle is broken at the alph-ketoglutarate step by denying Glucose and Glutamine (from protein rich dietary sources) for the synthesis of needed amino acids.

13 Ketogenesis

14 How is ketosis different? Ketone bodies are able to enter the TAC (step 2), while at the same time reducing NAD+ for inclusion in the ETC. This effectively eliminates the need for Glycolysis.

15 Bringing it all together

16 What does all this have to do with cancer? Basic premise is that cancer cells cannot metabolize the products of ketogenesis. Glucose transported via the bloodstream, is metabolized in the mitochondrial matrix of the individual cell. Cancer cells because of mitochondrial mutation derive their energy from lactic acid fermentation vs oxidative phosphorylation This has the effect of starving the cancer.

17 Supporting research Musselman et al. found correlational evidence of beneficial health changes under Ketosis. Further demonstrated patient that was cancer free after course of treatment.

18 Supporting research Victor et al. subjected subjects to varying levels of glucose in diet and monitored serum glucose. Celebrex was also added in addition to modified glucose. Results showed that switch from glycolysis to oxidative phosphorylation (internally to the tumor cells) caused a drop in serum lactic acid, and subsequently the ph, that promoted metastasis and accelerated growth of tumors

19 Supporting research Paoli et al. demonstrates the physiology behind Ketogenic diet. Illustrates the inability of fatty acids to cross the blood brain barrier. Establishes timeline for switch to keto metabolism. (2-6 hr). Further establishes correlation between keto metabolism and overall serum ph.

20 Supporting research Mathews et al. exhibits increased cell death rates when deprived of both Glucose and Glutamine. Glutamine is an important Amino Acid used in Gluconeogenesis. Study uses light microscopy to evaluate cell growth vs death. Further presents that drop in the level of Lactic Acid when glucose is deprived will start to produce tumors decline in as little as 2-6hr.

21 Ketogenic diet in practice Group members participated in trial diets to get a sense of the efficacy of the research. Diets were conducted with various modes of testing throughout. Main focus was on the production of Ketone bodies in urine and Glucose levels in blood. Other monitoring criteria included but were not limited to BMI, weight, Glucose Ketone Index, total carbs consumed.

22 What is the goal? Goal is to experience the effects of drastic carbohydrate reduction in diet. Aside from quanitative numbers derived from testing of body fluids. Qualitative information from participants on energy levels and other lifestyle information will be presented. A further questionnaire will demonstrate the level of comfort from a healthcare provider standpoint.

23 Ketones vs Carb Intake

24 Ketones vs Carb Intake

25 Ketones vs Carb Intake

26 Quantitative Results As the chart one shows, levels can change drastically from day to day depending on activity levels and carb intake. A correlation does appear after 3-4 days but levels quickly begin to diverge with minimal changes in carb intake.

27 Quantitative Results Obvious trend develops as carbs fall below 20grams/day Ketone levels begin to rise. For this subject even as a slight uptick in carbs takes place, ketones stay consistent.

28 Quanitative Results Clear trending is present in relation to carbohydrate intake Also clearly evident is the drastic decline in Ketone levels upon rising carb intake

29 Qualitative Results Participants had varied opinions on qualitative results Some experienced a drastic decline in energy levels, likely due to the abrupt decline in serum glucose levels. Some experienced varying levels of alertness through the day and likened the experience to being drunk. From a medical standpoint, glucose levels at varying times got dangerously low. Accepted normal values range from mg/dl, EVERY PARTICIPANT had at least a single episode of sub 35 mg/dl, some had multiple. Unrelated to cancer treatment, weight loss is easily achieved using these methods. As far as efficacy is concerned, as a weightless diet, the results are overwhelmingly positive.

30 Ketogenic Dieting Survey Results This survey questioned fifteen currently practicing physicians The physicians surveyed included MDs from all areas and specialties, but all focus primarily on adult patient populations The survey sought to identify current MDs understanding of the Ketogenic Diet and its possible utilization in the medical community

31 Continued Results: In your opinion do you think that Ketosis is harmful? 13 of 15 MDs view Ketosis as harmful 2 out of 15 MDs are not sure if Ketosis is harmful in every scenario; for example, Keto Diet in athletic young adults If so, can you explain a little bit about why it may be harmful. All MDs surveyed believe it to be a sign of starvation and malnutrition They report that this could lead to further complications in someone who is immunocompromised due to cancer, especially if used in addition to other cancer treatments such as chemotherapy or radiation

32 Have you ever heard of utilizing a Ketogenic diet in Cancer treatment? 15 out of 15 physicians surveyed had heard of the Ketogenic Diet 12 out of 15 had not heard of utilizing the Ketogenic diet in cancer treatment Do you think this diet could be useful in diminishing the growth of cancer? 0 of the 15 MDs think it could be useful in diminishing caner growth MDs seem skeptical of acknowledging usefulness due to a lack of exposure or experiences with this trial Results:

33 Survey Summaries: Would you ever consider recommending Ketogenic Dieting to a Cancer patient? All 15 surveyed physicians say no at this time All report that with increased research results, they may reconsider What research and results would you like to see before recommending this diet plan to someone with cancer? 11/15 MDs - Long-term cancer treatment results and cancer cell death 4 out of 15 MDs - Research showing there is no detrimental, long term side effects for patients being in ketosis while already immune compromised Do you think a Ketogenic Diet could be used for any other conditions? All 15 MDs acknowledge that they have not seen enough evidence based research to have an opinion on Keto Diet usage in symptom and disease management

34 Conclusion/ Discussion of Results While the science behind the ketodiet is taking shape, and initially positive, more research needs to be done. Many physicians are not convinced by current research. Participants had varying degrees of success with implementation. All participants got results, some were positive others were inconclusive. There is some degree of risk involved with undergoing the ketodiet, glucose levels likely will drop to dangerous levels and could result in the need for medical treatment. Given the alternatives for cancer patients, it may be a valuable tool if tumors respond positively.

35 Future development of Project Further research is need on the subject to truly demonstrate the risk vs benefit of diet. En vivo testing is the gold standard of medical research. As of yet no study has been published with the specific criteria of reducing or removing of cancer tumors via diet alone. The ability to culture cells and control the metabolic environment is beyond the scope of campus laboratory. This seems to be a natural next step and within the capability of most university labs.

36 Community References Survey was conducted on site at Washington Regional Medical center by resident physicians and healthcare providers.

37 References Ho, V. W., Hamilton, M. J., Dang, N. T., Hsu, B. E., Adomat, H. H., Guns, E. S.,... Krystal, G. (2014). A low carbohydrate, high protein diet combined with celecoxib markedly reduces metastasis. Carcinogenesis, 35(10), doi: /carcin/bgu147 Mathews, E. H., Stander, B. A., Joubert, A. M., & Liebenberg, L. (2014). Tumor cell culture survival following glucose and glutamine deprivation at typical physiological concentrations. Nutrition, 30(2), doi: /j.nut Paoli, A., Bosco, G., Camporesi, E. M., & Mangar, D. (2015). Ketosis, ketogenic diet and food intake control: A complex relationship. Frontiers in Psychology, 6. doi: /fpsyg Musselman, Amy. (2016). The Impact of Following a Ketogenic Diet and Intermittent Fasting Regimen on Chemotherapy- Induced Side-Effects and Overall Nutrition in a Patient with Ovarian Cancer: A case Report. Clinical Nutrition Week, 2016, Jan Denniston,K.,Topping, J., Dorr, D., Caret, R., (2017) General,Organic, and Biochemistry; 9th ed; (New York, NY) pp.782. Rohinisane Follow. (2015, February 16). Ketosis. Retrieved from Brent Cornell. (n.d.). Retrieved from Masino SA, Kawamura M, Wasser CD, Wasser CA, Pomeroy LT, Ruskin DN - Curr Neuropharmacol (2009)

The Ketogenic Diet and its Effect on Cancer.

The Ketogenic Diet and its Effect on Cancer. By: Josh Whittington, Bowman Fedosky, Shyann Graham, and Jordan Kennedy For: EMPACTS project Organic Physiological Chemistry with Dr. Chun Spring 2018 Abstract: