Keto-diet starter guide

A Parent’s Quick Guide to the Ketogenic Diet as an Adjunctive Cancer Treatment !

A MAXLOVE PROJECT FIERCE FOODS PUBLICATION Text: Justin Wilford, PhD Reviewed by Carrie Loughran, RD, LD and Miriam Kalamian, EdM, MS, CNS

A PARENT’S QUICK GUIDE TO THE KETOGENIC DIET

THE RATIONALE FOR THE KETOGENIC DIET AS A CANCER TREATMENT Overview The ketogenic diet (KD) is a very low-carbohydrate, adequate protein, high-fat diet. There are many different ways to do the diet but each type of KD has the common goals of 1) lowering blood glucose (i.e., blood sugar), 2) lowering insulin and insulin-like growth factor 1 (IGF-1) levels (the chemicals in our bodies that let our cells use blood sugar for energy) and 3) raising ketone bodies (i.e., biochemicals our livers produce from fat that our cells can use for energy in place of blood sugar). By altering the levels of these three substances in the blood, the KD is has been shown to suppress growth in many types of tumors.

How it works The tumor-suppressive effect of the KD is thought to occur through one or more of the following mechanisms:

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1. Scientists have known for almost 90 years that most solid cancers use blood sugar (glucose) as their primary source of energy (Vander Heiden 2009; Seyfried 2014). The German scientist Otto Warburg discovered that tumor cells consume glucose at a much higher rate than normal healthy cells. This has come to be known as the Warburg effect (Seyfried 2012). The KD decreases available glucose to tumor cells. This in itself might have a therapeutic effect. The most extensive human study to date (Fine 2012) has shown through PET scans that even mild ketosis (~1.5 BHB mml/dl) over the span of a month can significantly reduce glucose uptake (20%) in tumors of advanced cancer patients. Longer and more in-depth studies need to look at whether this decrease in glucose uptake translates into tumor regression. But smaller studies suggest that this relationship between between glucose levels and tumor progression (McGirtt 2008; Derr 2009) is real. 2. The KD increases circulating ketone bodies.  In a state of ketosis, ketone bodies are used by almost all normal cells but cannot be used by most cancer cells. A body in ketosis is more metabolically flexible because it is using both glucose and ketone bodies for energy production. While all normal cells can use either glucose or ketones for energy, the Warburg effect present in most cancers shows that cancer cells invariably have defective mitochondria that cannot make use of the alternative fuel in ketone bodies (Maurer 2011). Another way that ketosis might help is that a body in ketosis is making higher demands of mitochondria for energy production. This makes mitochondria work harder and so may serve to increase the effect of mitochondria's role as the body's housekeeper as it recycles old cellular parts or kills damaged cells. Perhaps potential cancerous cells are more likely to be disposed of in a ketotic environment (Champ and Klement 2014). 3. Because cancer cells rely on glucose to repair free radical damage, limiting glucose might also limit this reparative ability (Spitz 2000; Seyfried 2014). 4. The KD decreases circulating insulin and IGF-1, both of which are implicated in tumor progression. This is the hypothesis favored by Fine, et al (2012). Insulin and IGF-1 activate several metabolic pathways that are known to promote cancer growth and survival. Lower insulin should lead to an inhibition of these pathways. 5. The KD appears to increase the sensitivity and susceptibility of cancer cells to chemotherapy and radiation. To quote Colin E. Champ, a radiation oncologist and KD researcher: "Activation of the insulin

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receptor and several pathways downstream within cancer cells allows them to more readily fix damage from chemotherapy and radiation.  However, keep in mind that radiation therapy works mostly by interacting with the water molecules in and around cancer cells to create free radicals that attack the cancer cells, causing DNA damage.  Restricting glucose through a ketogenic diet may take advantage of this inability to counter damage from free radicals, making radiation more effective.  A study in mice has shown that radiation therapy efficacy is significantly increased in the face of a ketogenic diet when treating brain tumors." I have included this study (Abdelwahab 2012) plus another showing synergy with chemotherapy and radiation together (Allen 2013). 6. The KD appears to help the body’s immune system fight tumors. Researchers at Harvard University have recently published a series of papers describing how cancer hides from immune cells (Husain, et al 2013). The natural byproduct of tumors consuming an extremely high amount of glucose is lactate. The high levels of lactate in the tumor environment serve to hide the tumor from the body’s immune system. A KD lowers glucose metabolism and thus lowers the amount of lactate being produced by the tumor. This in turn allows for the immune cells to “see” the tumor better. 7. Lastly, some researchers speculate that ketones themselves might have some anti-cancer effect that is yet unknown. This hypothesis is currently being studied. In a recent study, researchers showed that ketone supplementation can reduce cancer growth even in the presence of high glucose (Poff et al 2014). This

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suggests that the ketones have an independent anticancer effect.

HOW TO BEGIN A KETOGENIC DIET FOR THE TREATMENT OF CANCER Partner with a ketogenic specialist If you haven’t already, sign up for our consultation program. We fully fund initial consultations with ketogenic dietitians who work long-distance. You should also check to see if your child’s hospital has a ketogenic clinic in their neurology department. The diet is widely used to treat patients with epilepsy. While the KD doesn’t have to be a difficult diet to follow and maintain for most kids and adults once they are in ketosis, challenges can emerge. A consultation with an experienced dietitian will help your child safely get into ketosis and maintain maximum health while on the diet.

Tell your oncologist that you intend to put your child on a ketogenic diet Expect your doctors to be highly skeptical of the ketogenic diet. But they also need to know that you are choosing to use this powerful therapy. To assuage your doctor’s fears you can tell him/her that Children’s Hospital of Orange County has passed a protocol to use the KD as an adjunctive cancer treatment and is presently treating several pediatric glioma patients with the KD. You can tell them that the University of Iowa is currently conducting human trials with the KD as a treatment for several different types of cancer. Mice studies have been and are being conducted at Boston College, Duke University, Yale University, and Barrow Neurological Institute in Phoenix. Share with them our review summary of the latest research on the KD and cancer. It can be found in the resource section at www.maxloveproject.org. Finally, if they remain skeptical or even disapproving, then remember that you are in

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charge and they are only advisors. Many parents have seen their doctors follow only after they start the diet. Once they see the child healthy and happy and in full ketosis, much of their fear subsides. And remember: the KD has been used for 90 years with epileptic children. It has been shown to be perfectly safe.

If it seems overwhelming then start slow Although your dietitian may want to start quickly with a fast, you may choose to start slow. Keep in mind that most dietitians will have experience only with epilepsy. In these cases the goal is to stop seizures as quickly as possible, and so the KD is initiated as quickly as possible. You and your child might be happier if you phase in the diet over the course of a couple weeks by first cutting out all sugar (this means honey, syrup, cane juice and fruit juices). After a few days of no sugar, cut out all refined carbohydrates (all pasta, white rice, chips, crackers and bread) and high-glycemic fruit (all fruit except for berries). After a few days of no sugar, refined carbohydrates, or highglycemic fruit, cut out all grains (no rice, wheat, oats, quinoa, millet, etc.) and all dairy except for butter, heavy cream, full fat sour cream, and a limited amount of fatty cheeses. By day 15 you are pretty much on the ketogenic diet. You might be wondering what you’re going to eat now that you’ve taken all this stuff out of your child’s diet. We’ll provide a quick list and a bunch of resources below.

Talk with your dietitian about supplementation Important supplements on the ketogenic diet include probiotics, sodium (salt), magnesium, potassium, calcium, and vitamin D. Potential supplements include omega-3 fatty acids (fish oil) and curcumin (turmeric).

Follow your child and get on a low-carbohydrate, high-fat diet with them. Many of the most popular diets today (Paleo, South Beach, Wheat Belly, Atkins) are low-carb, high-fat. Why? Because it is a very healthy diet and a very delicious one as well. It has been shown to be an effective treatment for obesity, metabolic syndrome, and diabetes. Emerging research is showing that it might also be effective for brain health, mood and anxiety regulation, and building physical endurance. It will make it much easier on your child if he/she sees you eating exactly as he/she does.

Don’t be discouraged by the KD’s dietary limitations It can be a wonderful and delicious way to eat! It’s not a joke: you can really eat eggs, bacon, butter, and heavy cream while on the diet and be extremely healthy! Saturated fat is not a killer, it is your friend.

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MAINTAINING THE KETOGENIC DIET Start testing glucose and ketone bodies (beta-hydroxybutyrate) The most accurate way to test both is with the Precision Xtra Blood Glucose and Ketone Monitoring System by Abbott Diabetes Care. You will need to use their small lancet to get a quick poke of blood, squeeze the blood into a small disposable strip that you insert into the monitor, and then wait a couple seconds for a reading to appear. The small poke is not fun for kids at first but it really is small and usually disappears within a minute or. Many

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parents offer a treat like a sugar-free candy after every poke. Some children start to ask for a poke in order to get the candy!

Become a keto-expert! The most important factor in maintaining the KD for you and your child is the level of your own knowledge of how the diet works and what sort of foods will deliver maximum benefit. Here are several resources that explain in lucid detail how a low-carbohydrate, high-fat diet works and how you can maintain it. • BOOKS Phinney, Stephen and Jeff Volek. 2012. The Art And Science Of Low Carbohydrate Performance. Lexington, KY: Beyond Obesity. ✓ Phinney, Stephen and Jeff Volek. 2011. The Art And Science Of Low Carbohydrate Living: An Expert Guide To Making The Life-Saving Benefits Of Carbohydrate Restriction Sustainable And Enjoyable. Lexington, KY: Beyond Obesity. ✓ Seyfried, Thomas. 2012. Cancer As a Metabolic Disease: On the Origin, Management, and Prevention of Cancer. New York: Wiley. ✓ Wahls, Terry. 2014. The Wahls Protocol. New York: Avery. ✓ Kalamian, Miriam. 2013. Get Started With The Ketogenic Diet For Cancer. Self-published eBook. ✓ Perlmutter, David. 2013. Grain Brain. The Surprising Truth About Wheat, Carbs, and Sugar. Hachette Book Group. KEY SCIENTIFIC JOURNAL ARTICLES, IN CHRONOLOGICAL ORDER (a summary of these articles is available in the resources section at www.maxloveproject.org) ✓ Nebeling, Linda C. and Edith Lerner. 1995. Implementing A ketogenic diet based on mediumchain triglyceride oil in pediatric patients with cancer. Journal of the American Dietetic Association 95 (6): 693 - 697. ✓ Kossoff, Eric H, et al. 2009. Optimal clinical management of children receiving the ketogenic diet: Recommendations of the international ketogenic diet study group. Epilepsia 50 (2): 304-317. ✓ Vander Heiden, M. G., Cantley, L. C., & Thompson, C. B. (2009). Understanding the warburg effect: The metabolic requirements of cell proliferation. Science, 324(5930), 1029-33. ✓ Skinner, Robert, Angelica Trujillo, Xiaojie Ma, and Elizabeth A Beierle. 2009. Ketone bodies inhibit the viability of human neuroblastoma cells. Journal of Pediatric Surgery 44 (1): 212-216. ✓ Stafford, Phillip, et al 2010. The ketogenic diet reverses gene expression patterns and reduces reactive oxygen species levels when used as an adjuvant therapy for glioma. Nutrition & Metabolism 7 (1): 74. ✓ Klement, Rainer J. and Ulrike Kämmerer. 2011. Is there a role for carbohydrate restriction in the treatment and prevention of cancer? Nutrition and Metabolism 8 (1):75. ✓ Scheck, Adrienne C, Mohammed G. Abdelwahab, Kathryn E. Fenton, and Phillip Stafford. 2012. The ketogenic diet for the treatment of glioma: Insights from genetic profiling. Epilepsy Research 100 (3): 327-37. ✓ Fine, Eugene J., et al. 2012. Targeting insulin inhibition as a metabolic therapy in advanced cancer: A pilot safety and feasibility dietary trial in 10 patients. Nutrition 28 (10): 1028-35. ✓ Fath, Melissa A., Andrean L Simons, and Jeffrey Erickson. 2012. Enhancement of cancer therapy using ketogenic diet. In Oxidative Stress in Cancer Biology and Therapy. Ed. Douglas R Spitz. Humana Press. ✓ Abdelwahab, Mohammed G., et al. 2012. The ketogenic diet is an effective adjuvant to radiation therapy for the treatment of malignant glioma. PLoS One 7 (5): e36197. ✓

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Allen, Bryan G, et al. 2013. Ketogenic diets enhance oxidative stress and radio-chemotherapy responses in lung cancer xenografts. Clinical Cancer Research. Author manuscript, online only. ✓ Poff, Angela M., Csilla Ari, Thomas N. Seyfried, and Dominic P. D’Agostino. 2013. The ketogenic diet and hyperbaric oxygen therapy prolong survival in mice with systemic metastatic cancer. PLoS One 8 (6): e65522. ✓ Husain, Zaheed, Yannu Huang, Pankaj Seth, and Vikas P. Sukhatme. 2013. Tumor-Derived lactate modifies antitumor immune response: Effect on myeloid-derived suppressor cells and NK cells. The Journal of Immunology 191 (3): 1486-1495. ✓ Klement, Rainer J. and Colin E. Champ. 2014. Calories, carbohydrates, and cancer therapy with radiation: Exploiting the five R's through dietary manipulation. Cancer Metastasis Rev 33 (1): 217-229. ✓ Seyfried, Thomas N., Roberto Flores, Angela M. Poff, and Dominic P. D’Agostino. 2014. Cancer as a metabolic disease: Implications for novel therapeutics. Carcinogenesis 35 (3): 515-527. ✓ Poff, AM, C. Ari, P. Arnold, T.N. Seyfried, and D.P. D'Agostino. 2014. Ketone supplementation decreases tumor cell viability and prolongs survival of mice with metastatic cancer. International Journal of Cancer. In press. ✓ Champ, Colin E., Joshua D. Palmer, Jeff S. Volek, Maria Werner-Wasik, David W. Andrews, James J. Evans, Jon Glass, Lyndon Kim, and Wenyin Shi. 2014. Targeting metabolism with a ketogenic diet during the treatment of glioblastoma multiforme. Journal of Neuroncology. In press. ✓ Mathews, Edward H., B. André Stander, Annie M. Joubert, and Leon Liebenberg. 2014. Tumor cell culture survival following glucose and glutamine deprivation at typical physiological concentrations. Nutrition 30 (2): 218-227. KEY BLOGS ON THE SCIENCE OF LOW-CARB, HIGH-FAT (KETOGENIC) DIETS ✓ Peter Attia, MD: www.eatingacademy.com ✓ Colin E. Champ, MD: http://www.cavemandoctor.com/category/cancer/ ✓ Richard David Feinman, PhD: http://rdfeinman.wordpress.com ✓ Dominic D’Agostino, PhD: http://ketonutrition.blogspot.com ✓ Peter “Hyperlipid”: http://high-fat-nutrition.blogspot.com ✓ Bill Lagakos, PhD: http://caloriesproper.com ✓ Robb Wolf: http://robbwolf.com/blog/ ✓ Andreas Eenfeldt, MD: http://www.dietdoctor.com/about ✓ Jimmy Moore: http://livinlavidalowcarb.com/blog/ KEY BLOGS FOR KETOGENIC RECIPES ✓ http://mariamindbodyhealth.com (she also has several keto-friendly books. Check her out on Amazon: Maria Emmerich) ✓ http://www.charliefoundation.org/recipes/ (a U.S.-based ketogenic diet advocacy group for epilepsy treatment) ✓ http://www.thepaleomom.com/recipes (she uses maple syrup and honey in some recipes so watch out) ✓ http://www.ketogenic-diet-resource.com/low-carb-recipes.html KEY WEBSITES FOR MORE INFORMATION ✓ The Charlie Foundation http://www.charliefoundation.org ✓ Miriam Kalamian, M.S., EdM., C.N.S.. (ketogenic diet health coach) http:// dietarytherapies.com ✓ Carrie Loughran, R.D. (ketogenic diet dietician) http://www.ketocare.com ✓ http://site.matthewsfriends.org (a UK-based ketogenic diet advocacy group for epilepsy treatment) ✓ Ellen Davis (ketogenic diet advocate) http://www.ketogenic-diet-resource.com ✓

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Get into a routine Many KDs are based on a specific ratio of calories consumed, e.g., 80% of calories from fat, 10% from protein, 10% from carbs. An easier way to do this is called the “Modified Atkins Diet” which restricts carbs but allows for liberty with protein and fat. For an anticancer ketogenic diet, it is important to keep protein restricted because protein can increase insulin and can be converted into glucose when consumed above a moderate amount. So a good rule of thumb is to keep carbohydrate intake to around 20 grams per day and protein around 1 gram per kg of body weight. Fat can always be eaten to satiety (fullness). This, of course, can be adjusted with your dietitian.

Stay as whole-foods as possible KetoCal is a shake that most hospitals use to induce and sometimes maintain ketosis. While some kids might need to start on ketocal, the KD can and should be maintained through whole foods. Because fats are such an important part of the KD, it is crucial to consume the highest quality fats. This means that all meat and dairy should be organic and grass-fed or pasture-raised if possible. Grass-fed, organic meat will ensure two things: a great reduction in harmful chemicals and hormones in the protein and fat, and a significant increase in good fats like omega-3 fatty acids. These products can be found in most health food grocery stores. But farmers markets are also a great option.

Stock up on the staples of a healthy KD A.

Fats (1) Butter, from grass-fed, pasture-raised animals (Organic Valley brand is the best, followed by Kerrygold) (2) Heavy Cream (if possible from grass-fed, pasture-raised animals) (3) Coconut Oil (virgin, cold-pressed) (4) MCT (Medium-Chain Triglyceride Oil, derived from coconut and palm oil) (5) Olive Oil (6) Macadamia Nuts (7) Avocados (8) Olives (9) Avoid all seed oils (corn oil, sunflower oil, canola oil, etc.) if possible. They are proinflammatory. B. Protein (1) Eggs (organic, omega-3) (2) Meat from organic, grass-fed, pasture-raised animals (don’t trim the fat) (3) Hot dogs from grass-fed, pasture-raised animals (Applegate brand) (4) Cheese from grass-fed, pasture-raised animals (look for highest fat-to-protein ratio) (5) Fatty fresh fish like Wild Salmon (6) Organic bacon (Applegate Brand) (7) Organic chicken (always served with fat-based sauce like hollandaise, bearnaise, ) C. Carbs (1) Veggies. We’ve only listed ones that most kids will eat. They should all be served in fat, either olive oil dressing, melted butter, or a cheese sauce (mixed with coconut oil or MCT oil). Be sure to include salt to taste: • Any type of leafy green (a whole head of green leaf lettuce only has 10 g of carbs) • Broccoli (1/2 cup cooked = 6 g of carbs/3g of fiber) • Cauliflower (1/2 cup cooked = 6 g of carbs/3g of fiber) • Asparagus (1/2 cup cooked = 4 g of carbs/2g of fiber) • Green beans (1 cup cooked = 10 g of carbs/4g of fiber) • Cucumber (1 whole = 4 g of carbs/1 g of fiber)

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• Carrots (8 baby carrots = 7 g of carbs/2 g of fiber) (2) Fruit. Most fruit and ALL juices are off the list. It is best to space out fruit consumption as well so that all 20 grams of allowed carbs don’t come at one sitting. Below are some good lowglycemic choices. 1. Berries (1 cup of halved strawberries = 12g of carbs/3 g of fiber) 2. Cherries (4 cherries = 4g of carbs/1g of fiber) 3. Apple slices (1 cup = 15g of carbs/3g of fiber)

It’s all in the numbers The great thing about the KD is that at the end of the day what matters is your child’s glucose and ketone numbers. This takes a lot of the guesswork out of the diet. Some kids (and adults) will be able to consume a little more carbs and protein and produce good numbers, while others will have to work a bit harder. Find the balance that’s right for you and your child. Don’t be afraid to experiment.

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