Fight Cancer with a Ketogenic Diet
Transcription
Fight Cancer with a Ketogenic Diet
A Safe, Science-Based, Non-Toxic Dietary Alternative for Cancer Treatment FIGHT CANCER WITH A Use the Warburg Effect to treat cancer at the metabolic level Minimize the unpleasant side effects of chemotherapy and radiation Improve the success rate of your standard treatment program Fight Cancer with a Ketogenic Diet A New Method for Treating Cancer Second Edition, January 2014 By Ellen Davis www.ketogenic-diet-resource.com All rights reserved. No part of this book, including interior design, cover design, and icons may be reproduced or transmitted in any form, by any means (electronic, photocopying, recording, or otherwise) without the prior written permission of the author, except for the inclusion of brief quotations in a review. Copyright 2013 by Ellen Davis Fight Cancer with a Ketogenic Diet (Clickable) Table of Contents .................................................................................. iii Dedication .............................................................................................................. vi Acknowledgements ............................................................................................... vii Using This Book .................................................................................................... viii Introduction .............................................................................................ix Chapter 1 ................................................................................................. 1 What is a Ketogenic Diet?........................................................................................ 1 Cancer Cells Are Sugar Addicts ................................................................................ 2 High Blood Glucose Fuels Cancer .................................................................................. 4 How Foods Affect Blood Glucose and Insulin ........................................................... 5 Ketogenic Diet: Why It Works .................................................................................. 7 Chapter 2 ................................................................................................. 9 The Scientific Evidence ............................................................................................ 9 What About Pediatric Cancer Treatment? ............................................................. 10 Chapter 3 ............................................................................................... 11 Who Should NOT Follow a Ketogenic Diet? ........................................................... 11 Contraindicated Metabolic Conditions ........................................................................ 11 Contraindicated Health Conditions.............................................................................. 11 Contraindicated Medications ...................................................................................... 12 Important Note on Steroids ........................................................................................ 12 Chemotherapy or Radiation Treatment ....................................................................... 12 Chapter 4 ............................................................................................... 13 Goals, Side Effects, Benefits, and Monitoring Progress .......................................... 13 Goal #1: Reduce Blood Glucose and Insulin, and Increase Ketones .............................. 14 Dr. Seyfried’s G/K Index ........................................................................................ 14 Notes on Carb, Protein and Caloric Restriction ...................................................... 16 Goal #2: Minimize and Treat Side Effects .................................................................... 17 About Heart Palpitations or a “Racing” Heart ........................................................ 21 Note on Elevated Cholesterol ............................................................................... 22 About Nausea ....................................................................................................... 22 Ketosis versus Ketoacidosis ................................................................................... 23 Benefits of a Ketogenic Diet ........................................................................................ 24 www.ketogenic-diet-resource.com iii Fight Cancer with a Ketogenic Diet Monitoring Progress ................................................................................................... 26 Laboratory Tests ................................................................................................... 26 Measuring Blood Glucose and Ketone Levels ........................................................ 27 Troubleshooting Stubborn Blood Glucose Levels ................................................... 28 Tips for Diet Success ................................................................................................... 30 Chapter 5 ............................................................................................... 33 Starting A Ketogenic Diet....................................................................................... 33 About Fats ............................................................................................................. 33 About Coconut Oil....................................................................................................... 34 About MCT Oil ............................................................................................................ 35 About Dairy Fats and Dairy Proteins ............................................................................ 35 About Protein ........................................................................................................ 37 About Glutamine ........................................................................................................ 37 About Carbohydrates ............................................................................................ 38 Calculating Total versus Net Carbs .............................................................................. 39 Increasing Carb Limits Over Time ................................................................................ 40 About Fiber ................................................................................................................. 41 About Water ......................................................................................................... 41 About Fasting and Intermittent Fasting ................................................................. 42 Fasting Tips ................................................................................................................. 43 My Personal Experience with Fasting .......................................................................... 44 Chapter 6 ............................................................................................... 45 Customizing Your Ketogenic Diet ........................................................................... 45 Step By Step Directions ............................................................................................... 45 Using the Food Exchange Lists .............................................................................. 50 Why Use Exchanges? ............................................................................................ 51 Meal Exchanges .......................................................................................................... 53 Tips on Using Your Customized Ketogenic Diet Plan .............................................. 54 Allowed Foods ....................................................................................................... 55 Foods To Avoid ...................................................................................................... 61 Reading Food Labels.............................................................................................. 64 Dining Out on a Ketogenic Diet.............................................................................. 65 General Tips................................................................................................................ 65 Tips for Specific Cuisines ............................................................................................. 65 Beware of Hidden Dining Pitfalls ................................................................................. 67 Travel Tips ............................................................................................................. 68 www.ketogenic-diet-resource.com iv Fight Cancer with a Ketogenic Diet Ketogenic Cooking Techniques .............................................................................. 69 Time Saving Cooking Tips ............................................................................................ 69 Quick Ketogenic Snack Ideas ....................................................................................... 70 Useful Kitchen Supplies ............................................................................................... 71 Recipe Resources ........................................................................................................ 71 Recommended Cookbooks.......................................................................................... 72 Chapter 7 ............................................................................................... 73 Other Factors to Consider ..................................................................................... 73 What about Exercise? ................................................................................................. 73 Alcohol Consumption .................................................................................................. 73 Stress .......................................................................................................................... 73 Illness, Medications and Menstrual Cycles .................................................................. 74 Sick Days ..................................................................................................................... 74 How Long Should I Stay on the Diet? ........................................................................... 75 Concerns about Acidity and Alkalinity ......................................................................... 75 Antioxidants................................................................................................................ 76 Ketogenic Diet and Vegetarianism: Not a Fit, But…...................................................... 76 Resources for More Information ........................................................................... 78 Final Words and Thank You ................................................................... 79 Appendices ............................................................................................ 80 Appendix A: Recommended Supplements ............................................................. 80 Appendix B: Recommended Health Professionals.................................................. 81 Appendix C: Suggested Ideal Weight Ranges ......................................................... 84 Appendix D: Daily Calorie Requirements ............................................................... 85 Appendix E: Ketogenic Macronutrient Levels ........................................................ 86 Appendix F: Macronutrient Worksheet ................................................................. 97 Appendix G: Food Exchange Lists .......................................................................... 99 Alphabetical Food Exchange List ............................................................................... 106 Appendix H: Exchange Record and Food Diary .................................................... 109 Appendix I: Meal Exchange Log ........................................................................... 111 Appendix J: Conversions and Measurements....................................................... 113 Appendix K: References ....................................................................................... 115 Appendix L: Glossary ........................................................................................... 119 www.ketogenic-diet-resource.com v Fight Cancer with a Ketogenic Diet A ketogenic diet (KD) emphasizes foods rich in natural fats and adequate in protein, and restricts foods high in carbohydrate. While the USDA recommendations call for 45-65% of calories from carbohydrate, ketogenic diets restrict carbohydrate intake to about 2-4% of calories. The charts at right compare food group intake between the Standard American Diet (SAD) and a ketogenic diet for cancer treatment. When carbohydrate containing foods (sugars and starches) are digested, they are broken down into blood sugar (glucose) in the body. The more carbohydrates we eat, the more glucose is made. High blood sugar is toxic to the body, so there are metabolic processes which push that sugar into our cells to be broken down into energy or fuel for the body. Only after this sugar has been metabolized can the body turn to using stored or dietary fat for energy needs. Reducing carbohydrate intake reduces blood glucose levels and this causes our internal biochemical pathways to switch to metabolizing fat and using the resulting products for energy. These fat derived substances are called ketone bodies. And once the body is using ketones as a main fuel source, there are some profound and positive health effects. Ketogenic diets are terrific for weight loss and addressing minor health issues such as heartburn and achy joints, however, they are much more powerful than those popular uses would suggest. In other words, this diet is not a “fad.” It is a potent regulator of metabolic derangement, and when formulated and implemented correctly, it can be extremely effective. In this eBook we will explore the details of this dietary approach and discuss how it works, why it works and how to implement it. www.ketogenic-diet-resource.com 1 Fight Cancer with a Ketogenic Diet In 1924, Dr. Otto Warburg, a Nobel Prize winning biochemist proposed the hypothesis that cancer is a metabolic disease. Dr. Warburg showed in his studies that cancer cells exhibited a preference for the utilization of sugar (glucose) as a fuel, even when the oxygen that normal cells use for energy creation was available. He wrote: “Cancer, above all other diseases, has countless secondary causes. But, even for cancer, there is only one prime cause. Summarized in a few words, the prime cause of cancer is the replacement of the respiration of oxygen in normal body cells by a fermentation of sugar.” ~Otto H. Warburg Until recently, Dr. Warburg’s hypothesis (known as the Warburg Effect) has been marginalized by the persistent belief in the oncology world that cancer is a genetic disease. However, in his new book, Cancer as a Metabolic Disease: On the Origin, Management, and Prevention of Cancer, Dr. Thomas Seyfried proposes the idea that Dr. Warburg was correct, and that cancer is instead a metabolic disease. Furthermore, the genetic markers on which the cancer research community has so fiercely focused are actually just downstream effects of the defective metabolism of cancer cells. What does it mean to say that cancer is a metabolic disease? Metabolic diseases are conditions in which the metabolism, or the making of energy from the food we eat, is broken or abnormal in some way. Normal body cells are able to create energy by using the food we eat and the oxygen we inhale to complete normal cellular “respiration” and make ATP (adenosine triphosphate), our main cellular energy source. Most of this energy production happens in the mitochondria, tiny organelles known as the “powerhouses” of the cell. There are two primary types of food-based fuel that our cells can use to produce energy: • The first cellular fuel is glucose, which is commonly known as blood sugar. Glucose is a product of the starches and sugars (carbohydrates) in our diet, and it is converted into energy in our cells via a process called glycolysis. In normal cells, glycolysis is an initial metabolic reaction which provides substrate molecules to the mitochondria so that the more effective and normal “oxygen dependent” cellular respiration can be completed. www.ketogenic-diet-resource.com 2 Fight Cancer with a Ketogenic Diet • The second type of cellular fuel comes from fatty acids. There are various kinds and they come from fats we eat or from the metabolism of stored fat from our fat cells. When blood glucose is low, fatty acids are broken down by the liver into products called ketone bodies or ketones. Ketones can be used by the mitochondria of most cells to produce energy. The process of creating ketones is called ketogenesis, and the metabolic state which favors using ketones as the primary source of energy is called ketosis. When glucose levels are low, most normal cells will switch to using ketone bodies for fuel. Ketones allow normal cells to be metabolically flexible, so to speak. Even the brain and nerve cells, which are heavily dependent on glucose, can utilize ketone bodies for fuel. This ability of most normal cells to use ketones (when glucose is unavailable) indicates that their cellular mitochondria are healthy and functioning properly. In contrast, most cancer cells have dysfunctional mitochondria and limited metabolic flexibility. They can’t access mitochondrial energy pathways so they can’t utilize ketones, which leaves only the pathway of glycolysis (shown on the right side of the picture below): Photo Credit: http://hyperphysics.phy-astr.gsu.edu/hbase/biology/celres.html This lack of flexibility leaves cancer cells dependent on glycolysis and other less efficient forms of cellular energy production to keep themselves alive. In fact, this metabolic inflexibility is why a ketogenic diet can effect cancer cells. By lowering glucose levels in the blood, the KD exploits the Achilles heel of cancer cells by forcing them to literally “run out of fuel.” www.ketogenic-diet-resource.com 3 Fight Cancer with a Ketogenic Diet While our brain depends on glucose for part of its energy needs, some cells such as our red blood cells are entirely dependent on glucose for survival. Since glucose is so crucial for life, several metabolic mechanisms are in place to ensure that blood sugar remains at steady levels necessary to support the needs of the body. Insulin is the primary hormone involved in the regulation of glucose levels in the body. Insulin is made by cells in the pancreas, mostly in response to a rise in glucose levels that accompanies digestion of foods containing carbohydrates. Insulin’s function is to “push” blood sugar into cells where it can be metabolized for cellular energy. This works great until a few hours after a meal. At that point, insulin has completed its job and blood sugar levels begin to drop. If the next meal is skipped or delayed, a different hormone, glucagon, calls on the liver to release a stored form of glucose called glycogen. The liver may also produce new glucose from “precursor” molecules in a process called gluconeogenesis. The image at right is from a study which looked at carbohydrate metabolism and its effects on insulin and blood glucose. It’s a good example of how insulin and blood glucose rise in lock step when carbohydrates are consumed. Whenever we eat a large amount of carbohydrates, our digestive system breaks them down into blood glucose. Each time blood glucose surges, the pancreas makes insulin and releases it into the bloodstream. More insulin in the bloodstream means that more glucose will get pushed into cells. Cancer cells are primed to take advantage of this extra glucose for growth, so lowering glucose and insulin in the bloodstream is a priority. www.ketogenic-diet-resource.com 4 Fight Cancer with a Ketogenic Diet Blood glucose and insulin levels are regulated in part by the types and amounts of foods we eat and digest. Foods in the human diet are composed of several important macronutrients: fats, carbohydrates, and proteins. Upon digestion in the body, each of these macronutrients has a different effect on blood glucose and insulin: Macronutrient/Foods Most dietary Fats and oils are in the form of “triglycerides” which can be either saturated, monounsaturated, or polyunsaturated. Effect on blood glucose and insulin upon digestion Fats have little to NO effect on blood glucose or insulin levels. Proteins are primarily found in foods such as meats, eggs, poultry, fish and some plant foods (e.g. soy, nuts and beans). During digestion, proteins are broken down into smaller units called amino acids. Proteins have a moderate effect on blood glucose and insulin. The more protein consumed, the greater the effect. In addition, certain amino acids have a pronounced effect on blood glucose and cancer cell metabolism. Carbohydrates (carbs) are found in foods such as fruits, vegetables, beans, grains (e.g. wheat, rice and corn) and all starchy or sweet foods. Upon digestion, carbohydrates are broken down into simple sugars (glucose, galactose and fructose). Carbohydrates have the greatest effect on blood glucose and insulin. Carbs eaten in any amount or form will raise blood glucose and cause a rise in insulin to push blood glucose into cells. Most whole foods are a combination of the three macronutrients, usually with one macronutrient being the “dominant” one. The exception to this rule is in the case of highly processed foods such as doughnuts or French fries. Processed foods are usually high in both fat and carbohydrate, a particularly unnatural combination. Whole foods, on the other hand, have healthier ratios. If a whole food such as an avocado is high in fat, it will most likely be low in protein and carbohydrate. If a whole food like steak or chicken breast is mostly protein, it will likely be moderate in fat and low in carbohydrate. Our food nourishes us in a loose three-way “ratio” and understanding this ratio will help you design www.ketogenic-diet-resource.com 5 Fight Cancer with a Ketogenic Diet meals consistent with a ketogenic diet. Here are a few examples of how the calorie percentage ratios work in real foods: Olive Oil: olive oil is 100% fat, with 0% carbohydrate and 0% protein. Baked Potato: a plain white potato is 80% carbohydrate, 10% non-digestible fiber, 10% protein and 0% fat. Chicken Breast: a baked chicken breast is 62% protein, 38% fat and 0% carbohydrate. Raw Spinach: raw spinach is 30% carb, 30% non-digestible fiber and surprisingly, 40% protein. Here’s a visual representation of those percentages: Understanding and managing these ratios will help you determine what foods to eat so you consume correct amounts of each macronutrient. The overall target of a ketogenic diet is to maximize fat intake, limit protein to what is needed for “repair and maintenance,” and restrict carbohydrate intake. When carbohydrate and protein intake are controlled and fat intake is emphasized, circulating blood glucose and insulin will remain low and stable AND there will be a corresponding rise in ketone body production. The metabolic state of elevated ketones coupled with low blood sugar and insulin is called nutritional ketosis and this is our goal. Getting to and staying in the state of nutritional ketosis is how we create an inhospitable metabolic environment for cancer cells. www.ketogenic-diet-resource.com 6 Fight Cancer with a Ketogenic Diet Adhering to a ketogenic diet and staying in a state of nutritional ketosis has the effect of changing the body’s metabolic environment into one that is incompatible with cancer cell metabolism. Cancer cells thrive on high levels of glucose and depend on high insulin levels to obtain that glucose. High insulin levels also set the stage for increased production of other hormones which enhance the metabolic conditions for cancer advancement. A ketogenic diet emphasizes the consumption of fats because these foods have almost no effect on blood glucose and insulin levels. In contrast, sugars and starches (foods high in carbohydrate) elevate blood glucose and insulin significantly. Excess protein will elevate blood glucose as well. Lowering carbohydrate and protein intake while increasing fat consumption effectively bottlenecks the sugary fuel that drives cancer growth. In response to the bottleneck, the liver creates ketone bodies from stored and dietary fat to supply energy the body needs. Once glucose supply is limited and ketones are elevated, food supplies for cancer cells get scarce. In addition, lower levels of insulin inhibit hormones such as insulin-like growth factor 1 (IGF1) and other metabolic pathways which promote cancer progression. And that’s not all. Because cancer cells have defective mitochondria, low glucose supplies leave them with no way to repair the oxidative stress which constantly bombards all cells. Hence they are more likely to sustain fatal injuries from interactions with oxidizing free radicals. Radiation therapy works by increasing free radical activity around cancer tissue and studies have shown that being in nutritional ketosis seems to enhance this destructive free radical effect. Meanwhile, normal cells thrive in this new metabolic environment since they can metabolize ketone bodies quite well. In fact, switching to ketones for energy needs results in a lower rate of oxidative damage in normal cells. So not only are cancer cells endangered, normal cells sustain less free radical damage and get a boost toward good health when a ketogenic diet is adopted. This ability of normal cells to switch fuel states from glucose to ketones (i.e., nutritional ketosis) is a crucial adaptation which has most likely permitted our continued survival on planet Earth. Ketone bodies act as a backup system when blood glucose levels fall, either as a result of starvation or carbohydrate restriction. Without this adaptation, the human race from Paleolithic man to the modern castaway might have perished during times when food was in short supply. www.ketogenic-diet-resource.com 7 Fight Cancer with a Ketogenic Diet Put another way, a ketogenic diet has a sort of domino effect on cancer. It lowers high blood sugar which reduces insulin levels in the blood. Reducing insulin levels effectively inhibits the production of IGF-1. In turn, low insulin and low IGF-1 levels inhibit other hormonal drivers of cancer like TAF (tumor angiogenesis factor), a substance that cancer cells secrete in order to build a blood supply network for themselves. And to top it all off, low glucose supplies leave cancer cells without a way to repair free radical damage, and this compromises their ability to survive. This antioxidant and anti-inflammatory effect of nutritional ketosis is why calorie restriction, fasting and ketogenic diets (which produce ketones and mimic fasting without the hunger) have such beneficial effects on human health. In fact, nutritional ketosis and ketone bodies themselves are being studied extensively as a treatment for many metabolic diseases. A growing number of research papers have been published on ketogenic diets and the anti-inflammatory effect Lower IGF-1 of ketone bodies on conditions such as epilepsy, Multiple Sclerosis, ALS, Lower Lower TAF Parkinson’s Disease, Alzheimer’s Insulin Disease, head trauma, Type 2 Diabetes, cardiovascular disease, autism, migraine headaches, stroke, Lower Increased Cancer Cell Starvation Blood Free Radical depression, acne and of course, and Death Glucose Damage cancer. This is all rather technical, so I’ll end this section with the short story: to fight cancer, it is crucial that you lower blood glucose and insulin levels and increase circulating ketone bodies. This is exactly what a ketogenic diet does. www.ketogenic-diet-resource.com 8 Fight Cancer with a Ketogenic Diet Abdelwahab MG, Fenton KE, Preul MC, Rho JM, Lynch A, Stafford P, Scheck AC. The ketogenic diet is an effective adjuvant to radiation therapy for the treatment of malignant glioma. PLoS One. 2012;7(5):e36197. Al-Sarraj T, Saadi H, Volek JS, Fernandez ML. Metabolic syndrome prevalence, dietary intake, and cardiovascular risk profile among overweight and obese adults 18-50 years old from the United Arab Emirates. Metab Syndr Relat Disord. 2010 Feb;8(1):39-46. Al-Sarraj T, Saadi H, Volek JS, Fernandez ML. Carbohydrate restriction favorably alters lipoprotein metabolism in Emirati subjects classified with the metabolic syndrome. Nutr Metab Cardiovasc Dis. 2010 Dec;20(10):7206. Berardi, MJ and Fantin, VR. Survival of the fittest: metabolic adaptations in cancer. Curr Opin Genet Dev. 21(1): p. 59-66. Berkeley HeartLab website. Clinician’s Reference Manual Online. Available at http://www.bhlinc.com/clinicians/clinical-references/reference-manual/chapter17 Accessed August 26, 2013. Cahill GF Jr, Veech RL. Ketoacids? Good medicine? Trans Am Clin Climatol Assoc. 2003;114:149-61; discussion 162-3. Review. Cahill GF Jr. Starvation in man. N Engl J Med 1970;282:668–75. Champ, Colin. Caveman Doctor Blog. An introduction: A Ketogenic Diet for Cancer. Available at http://www.cavemandoctor.com/2013/01/01/an-introduction-a-ketogenic-diet-for-cancer/. Accessed January 6, 2014. Chen W, Wang S, Tian T, Bai J, Hu Z, Xu Y, Dong J, Chen F, Wang X, Shen H. Phenotypes and genotypes of insulin-like growth factor 1, IGF-binding protein-3 and cancer risk: evidence from 96 studies. Eur J Hum Genet. 2009 Dec;17(12):1668-75 Després JP, Lamarche B, Mauriège P, Cantin B, Dagenais GR, Moorjani S, Lupien PJ. Hyperinsulinemia as an independent risk factor for ischemic heart disease. N Engl J Med. 1996 Apr 11;334(15):952-7. Derr RL, Ye X, Islas MU, et al. Association between hyperglycemia and survival in patients with newly diagnosed glioblastoma. J Clin Oncol. 2009 Mar 1;27(7):1082-6. Evangeliou A, Vlachonikolis I, Mihailidou H, Spilioti M, Skarpalezou A, et al. Application of a ketogenic diet in children with autistic behavior: pilot study. J Child Neurol. 2003 Feb;18(2):113-8. Fine EJ, Miller A, Quadros EV, Sequeira JM, Feinman RD. Acetoacetate reduces growth and ATP concentration in cancer cell lines which over-express uncoupling protein 2. Cancer Cell Int. 2009 May 29;9:14. Fine EJ, Segal-Isaacson CJ, Feinman RD, Herszkopf S, Romano M, Tomuta N, Bontempo A, Sparano JA: A pilot safety and feasibility trial of a reduced carbohydrate diet in individuals with advanced cancer. J Clin Oncol 2011, 29 (suppl; abstr e13573). rd Frayn, K. Metabolic Regulation: A Human Perspective, 3 Edition. Oxford: Wiley-Blackwell, 2010. Gahete M et al. The consequences of changing endogenous GH/IGF1 levels on carcinogen-induced mammary gland tumorigenesis are dependent on metabolic status in mice. Endocrine Abstracts (2013) 32 OC1.1. Gardner CD, Kiazand A, Alhassan S, Kim S, Stafford RS, Balise RR, Kraemer HC, King AC. Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related risk factors among overweight premenopausal women: the A TO Z Weight Loss Study: a randomized trial. JAMA. 2007 Mar 7;297(9):969-77. Erratum in: JAMA. 2007 Jul 11;298(2):178. Hartmann S, Lacorn M, Steinhart H. Natural occurrence of steroid hormones in food. Food Chemistry. Volume 62, Issue 1, May 1998, Pages 7–20. www.ketogenic-diet-resource.com 115 Fight Cancer with a Ketogenic Diet Harvey AE, Lashinger LM, Otto G, Nunez NP, Hursting SD. Decreased systemic IGF-1 in response to calorie restriction modulates murine tumor cell growth, nuclear factor-kB activation, and inflammationrelated gene expression. Mol Carcinog. 2012 Jul 6. Hu G, Qiao Q, Tuomilehto J, Eliasson M, Feskens EJ, Pyorala K. Plasma insulin and cardiovascular mortality in non-diabetic European men and women: a meta-analysis of data from eleven prospective studies. Diabetologia 2004 July;47(7):1245-56. Kabat GC, Kim M, Caan BJ, Chlebowski RT, Gunter MJ, Ho GY, Rodriguez BL, Shikany JM, Strickler HD, Vitolins MZ, Rohan TE. Repeated measures of serum glucose and insulin in relation to postmenopausal breast cancer. Int J Cancer. 2009 Dec 1;125(11):2704-10. Kang HC, Chung da E, Kim DW, Kim HD: Early- and late-onset complications of the ketogenic diet for intractable epilepsy. Epilepsia 2004, 45:1116-1123. Kiebish et al. Cardiolipin and electron transport chain abnormalities in mouse brain tumor mitochondria: lipidomic evidence supporting the Warburg theory of cancer. The Journal of Lipid Research, 2008; 49 (12): 2545. Kern KA, Norton JA. Cancer cachexia. JPEN J Parenter Enteral Nutr. 1988 May-Jun;12(3):286-98. Review. Kim HS, Masko EM, Poulton SL, Kennedy KM, Pizzo SV, Dewhirst MW, Freedland SJ. Carbohydrate restriction and lactate transporter inhibition in a mouse xenograft model of human prostate cancer. BJU Int. 2012 Oct;110(7):1062-9. Klement RJ, Champ CE. Calories, carbohydrates, and cancer therapy with radiation: exploiting the five R's through dietary manipulation. Cancer Metastasis Rev. 2014 Jan 17. Klement RJ, Kämmerer U. Is there a role for carbohydrate restriction in the treatment and prevention of cancer? Nutr Metab (Lond.) 2011 Oct 26;8:75. Kossoff EH, Hartman AL. Ketogenic diets: new advances for metabolism-based therapies. Curr Opin Neurol. 2012 Apr;25(2):173-8. Kraft BD, Westman EC. Schizophrenia, gluten, and low-carbohydrate, ketogenic diets: a case report and review of the literature. Nutr Metab (Lond.) 2009 Feb 26;6:10. Lund TM, Obel LF, Risa Ø, Sonnewald U. β-Hydroxybutyrate is the preferred substrate for GABA and glutamate synthesis while glucose is indispensable during depolarization in cultured GABAergic neurons. Neurochem Int. 2011 Aug;59(2):309-18. Maalouf M, Rho JM, Mattson MP. The neuroprotective properties of calorie restriction, the ketogenic diet, and ketone bodies. Brain Res Rev. 2009 Mar;59(2):293-315. Malek M, Aghili R, Emami Z, Khamseh ME. Risk of Cancer in Diabetes: The Effect of Metformin. ISRN Endocrinol. 2013 Sep 24;2013:636927. Review. Manley SE, Stratton IM, Clark PM, Luzio SD. Comparison of 11 human insulin assays: implications for clinical investigation and research. Clin Chem 2007 May;53(5):922-32. Marsh J, Mukherjee P, Seyfried T. Drug/diet synergy for managing malignant astrocytoma in mice: 2-deoxy-Dglucose and the ketogenic diet. Nutrition & Metabolism 2008, 5:33 (25 November 2008). Maurer GD, Brucker DP, Bähr O, Harter PN, Hattingen E, Walenta S, Mueller-Klieser W, Steinbach JP, Rieger J. Differential utilization of ketone bodies by neurons and glioma cell lines: a rationale for ketogenic diet as experimental glioma therapy. BMC Cancer. 2011 Jul 26;11:315. Milder J, Patel M. Modulation of oxidative stress and mitochondrial function by the ketogenic diet. Epilepsy Res. 2012 Jul;100(3):295-303. Mozaffarian D, Rimm EB, Herrington DM. Dietary fats, carbohydrate, and progression of coronary atherosclerosis in postmenopausal women. Am J Clin Nutr. 2004 Nov;80(5):1175-84. www.ketogenic-diet-resource.com 116 Fight Cancer with a Ketogenic Diet Mulrooney TJ, Marsh J, Urits I, Seyfried TN, Mukherjee P. Influence of caloric restriction on constitutive expression of NF-κB in an experimental mouse astrocytoma. PLoS One. 2011 Mar 30;6(3):e18085. Nebeling LC, Miraldi F, Shurin SB, Lerner E. Effects of a ketogenic diet on tumor metabolism and nutritional status in pediatric oncology individuals: two case reports. J Am Coll Nutr 1995;14:202–208. Oleksyszyn J. The complete control of glucose level utilizing the composition of ketogenic diet with the gluconeogenesis inhibitor, the anti-diabetic drug metformin, as a potential anti-cancer therapy. Med Hypotheses. 2011 Aug; 77(2):171-3. Otto H. Warburg, The Prime Cause and Prevention of Cancer accessed March 7, 2013. Paoli A, Rubini A, Volek JS, Grimaldi KA. Beyond weight loss: a review of the therapeutic uses of very-lowcarbohydrate (ketogenic) diets. European Journal of Clinical Nutrition (2013) 67, 789–796. Parekh N, Lin Y, Hayes RB, Albu JB, Lu-Yao GL. "Longitudinal associations of blood markers of insulin and glucose metabolism and cancer mortality in the third National Health and Nutrition Examination Survey." Cancer Causes Control. 2010 Apr;21(4):631-42. Phelps JR, Siemers SV, El-Mallakh RS. The ketogenic diet for type II bipolar disorder. Neurocase. 2012 Oct 3. Ristow M, Schmeisser S. Extending life span by increasing oxidative stress. Free Radical Biology and Medicine 51:327-336, 2011. Sayin VI, Ibrahim MX, Larsson E, Nilsson JA, Lindahl P, Bergo MO. Antioxidants accelerate lung cancer progression in mice. Sci Transl Med. 2014 Jan 29;6(221):221ra15. Scheck AC, Abdelwahab MG, Fenton KE, Stafford P. The ketogenic diet for the treatment of glioma: insights from genetic profiling. Epilepsy Res. 2012 Jul;100(3):327-37. Schmidt M, Pfetzer N, Schwab M, Strauss I, Kämmerer U. Effects of a ketogenic diet on the quality of life in 16 individuals with advanced cancer: A pilot trial. Nutr Metab (Lond.) 2011 Jul 27;8(1):54. Seyfried TN, Flores R, Poff AM, D'Agostino DP. Cancer as a Metabolic Disease: Implications for Novel Therapeutics. Carcinogenesis. 2013 Dec 16. Seyfried BT, Kiebish M, Marsh J, Mukherjee P. Targeting energy metabolism in brain cancer through calorie restriction and the ketogenic diet. J Cancer Res Ther. 2009 Sep;5 Suppl 1:S7-15. Seyfried TN, Kiebish MA, Marsh J, Shelton LM, Huysentruyt LC, Mukherjee P. Antiangiogenic and Proapoptotic Effects of Dietary Restriction on Experimental Mouse and Human Brain Tumors. Clin Cancer Res. August 15, 2004 10; 5622. Seyfried TN, Kiebish MA, Marsh J, Shelton LM, Huysentruyt LC, Mukherjee P. Metabolic management of brain cancer. Biochim Biophys Acta. 2011 Jun;1807(6):577-94. Seyfried TN, Marsh J, Shelton LM, Huysentruyt LC, Mukherjee P. Is the ketogenic diet a viable alternative to the standard of care for managing malignant brain cancer? Epilepsy Res. 2012 Jul;100(3):310-26. Seyfried TN, Mukherjee P. Anti-Angiogenic and Pro-Apoptotic Effects of Dietary Restriction in Experimental Brain Cancer: Role of Glucose and Ketone Bodies. In: Meadows GG, editor. Integration/Interaction of Oncologic Growth. 2 nd ed. New York: Kluwer Academic; 2005. Seyfried TN, Sanderson TM, El-Abbadi MM, McGowan R, Mukherjee P. Role of glucose and ketone bodies in the metabolic control of experimental brain cancer. Br J Cancer. 2003 Oct 6;89(7):1375-82. Spitz DR, Sim JE, Ridnour LA, et al. Glucose deprivation-induced oxidative stress in human tumor cells. A fundamental defect in metabolism? Ann N Y Acad Sci. 2000;899:349-62. Stafford P, Abdelwahab M, Kim D, Preul M, Rho J, Scheck A. The ketogenic diet reverses gene expression patterns and reduces reactive oxygen species levels when used as an adjuvant therapy for glioma. Nutr Metab 2010, 7:74 (10 September 2010. www.ketogenic-diet-resource.com 117 Fight Cancer with a Ketogenic Diet Stafstrom C, Rho J. The Ketogenic Diet as a Treatment Paradigm for Diverse Neurological Disorders. Front Pharmacol. 2012;3:59. Tsilidis KK, et al. Insulin-like growth factor pathway genes and blood concentrations, dietary protein and risk of prostate cancer in the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). : Int J Cancer. 2013 Jul 15;133(2):495-504. doi: 10.1002/ijc.28042. Epub 2013 Feb 15. Vendramini-Costa DB, Carvalho JE. Molecular link mechanisms between inflammation and cancer. Curr Pharm Des. 2012;18(26):3831-52. Review. Volek J, Phinney S. The Art and Science of Low Carbohydrate Living: An Expert’s Guide to Making the LifeSaving Benefits of Carbohydrate Restriction Sustainable and Enjoyable. Miami: Beyond Obesity: 2011. Volek J, Phinney S. The Art and Science of Low Carbohydrate Performance. Miami: Beyond Obesity: 2012. Wang J, Li G, Wang Z, Zhang X, Yao L, Wang F, Liu S, Yin J, Ling EA, Wang L, Hao A. High glucose-induced expression of inflammatory cytokines and reactive oxygen species in cultured astrocytes. Neuroscience. 2012 Jan 27;202:58-68. Wang Q, Bailey CG, Ng C, Tiffen J, Thoeng A, Minhas V, Lehman ML, Hendy SC, Buchanan G, Nelson CC, Rasko JE, Holst J. Androgen receptor and nutrient signaling pathways coordinate the demand for increased amino acid transport during prostate cancer progression. Cancer Res. 2011 Dec 15;71(24):7525-36. Warburg O. On the origin of cancer cells. Science 1956;123:309–314. Warburg O. The chemical constitution of respiration ferment. Science. 1928;68:437–443. Warburg OH. The classic: The chemical constitution of respiration ferment. Clin Orthop Relat Res. 2010 Nov;468(11):2833-9. Reprint. Wise, DR and Thompson, CB. Glutamine addiction: a new therapeutic target in cancer. Trends Biochem Sci. 35(8): p. 427-33. Wood PA. How Fat Works, Chapters 5 and 16. Harvard University Press, Cambridge MA, 2006. Yang X, Cheng B. Neuroprotective and anti-inflammatory activities of ketogenic diet on MPTP-induced neurotoxicity. J Mol Neurosci. 2010 Oct;42(2):145-53. Zelickson, BR, Ballinger SW, Dell'Italia LJ, Zhang J, Darley-Usmar VM. Reactive Oxygen and Nitrogen Species: Interactions with Mitochondria and Pathophysiology, In: Editors-in-Chief: William J. Lennarz and M. Daniel Lane, Editor(s)-in-Chief, Encyclopedia of Biological Chemistry, Academic Press, Waltham, 2013, Pages 17-22. Zhao MD, Hu XM, Sun DJ, Zhang Q, Zhang YH, Meng W. Expression of some tumor associated factors in human carcinogenesis and development of gastric carcinoma. World J Gastroenterol. 2005 Jun 7;11(21):321721. Zhou W, Mukherjee P, Kiebish MA, Markis WT, Mantis JG, Seyfried TN. The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer. Nutr Metab (Lond) 2007;4:5. Zuccoli G, Marcello N, Pisanello A, Servadei F, Vaccaro S, Mukherjee P, Seyfried TN. Metabolic management of glioblastoma multiforme using standard therapy together with a ketogenic diet: Case Report. Nutr Metab (Lond.) 2010 Apr 22;7:33. Zupec-Kania B. Modified Ketogenic Diet Therapy. The Charlie Foundation for Ketogenic Diet Therapies, 2013. www.ketogenic-diet-resource.com 118