Ketogenic Diet. Dr Damien Downing. With thanks to Dr Heinz Reinwald

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1 Ketogenic Diet Dr Damien Downing With thanks to Dr Heinz Reinwald

2 Ketogenic Diet What?

3 We were designed to be oil-fuelled, the mechanism is in every cell Peroxisomes break down the long chain lipids Carnitine with Carnitine XXXoyl Transferases transports them into mitochondria burnt for energy

4 Oil-fuelled, not sugar-fuelled CHOs require a complex hormone produced by few clumps of cells in one organ; Insulin From the islets of Langerhans In the pancreas

5 For most of our evolution we were oil-fuelled

6 Cain [farmer] slew Abel [shepherd] in a fit of rage

7 2. Glukogenic Age until about 1850 Rise of Civilisation 77

8 92 3. Glukotoxic Age: today Industrializing period: refined sugar and refined wheat (1970: transgenic wheat /HFCS)

9

10 Ketogenic Diet Why?

11 Mark 9:16-29 Teacher, I brought my son to you, for he has a spirit that makes him mute. And whenever it seizes him, it throws him down, and he foams and grinds his teeth and becomes rigid. This kind can come forth by nothing, but by prayer and fasting.

12 110

13

14 FOURTH GLOBAL SYMPOSIUM DIETARY THERAPIES FOR EPILEPSY & OTHER NEUROLOGICAL DISORDERS LIVERPOOL HILTON HOTEL, United Kingdom 7 TH 11 TH OCTOBER 2014

15 The use of ketones in the brain HCD VLCKD 13 In prolonged fasting the brain can derive 70%? 90%? of energy from ketones without adverse effect

16 Drenick, E. J., Alvarez, L. C., Tamasi, G. C., & Brickman, a. S. (1972). Resistance to symptomatic insulin reactions after fasting. Journal of Clinical Investigation, 51(10), doi: /jci107095

17 Glucose concentrations as low as 0.5 mmoles/litre (9 mg/100 ml) failed to precipitate hypoglycemic reactions. Drenick, E. J., Alvarez, L. C., Tamasi, G. C., & Brickman, a. S. (1972). Resistance to symptomatic insulin reactions after fasting. Journal of Clinical Investigation, 51(10), doi: /jci107095

18 Ketogenic Diet mechanisms Paoli, a, Rubini, A, Volek, J. S., & Grimaldi, K. a. (2013). doi: /ejcn

19 Epilepsy Ketogenic Diet for: Alzheimer s Parkinson s Obesity Diabetes High cholesterol and Cancer

20 The science, all in one place

21 Sugars Burn in 11 metabolic steps Feed cancer cells (90% are glucose-dependent) IGF-1 is, well, a Growth Factor Pro-inflammatory Tumours promote insulin resistance

22 Ketones Burn in 3 metabolic steps Reduce ROS production Improve mitochondrial function Anti-inflammatory White, H., & Venkatesh, B. (2011). Clinical review: Ketones and brain injury. Critical Care, 15(2), 219. doi: /cc10020

23

24 Ketones Anti-inflammatory Youm, Y.-H., Nguyen, K. Y., Grant, R. W., et al (2015). The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome mediated inflammatory disease. Nature Medicine, 1 9. doi: /nm.3804

25 Ketogenic Diet alone, or Integrated Therapy? British Society for Integrative Oncology promotes the integration of orthodox and complementary medicine to improve the lives of people affected by cancer in the UK What Magic Bullet?

26 Integrative therapy Abdelwahab, M. G., Fenton, K. E., Preul, M. C., Rho, J. M., Lynch, A., Stafford, P., & Scheck, A. C. (2012). The ketogenic diet is an effective adjuvant to radiation therapy for the treatment of malignant glioma. PLoS ONE, 7(5), 1 7. doi: /journal.pone

27 Ketogenic Diet & Radiation % survival SD KD Rad KD + Rad Days Abdelwahab, M. G., Fenton, K. E., Preul, M. C., et al (2012). doi: /journal.pone

28

29 Fine, E. J., Segal-Isaacson, C. J., Feinman, R. D., 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), doi: /j.nut Nutrition , DOI: ( /j.nut )

30 Degree of Ketosis & Tumour Size % change in tumour Ratio beta-ohb post/pre diet Fine, E. J., Segal-Isaacson, C. J., Feinman, R. D. et al (2012).Nutrition, 28(10), doi: /j.nut

31 Ketogenic Diet How? Three secret weapons

32 Ketogenic Diet Secret weapons 1. Glucose/Ketone Meter

33

34

35 1. Glucose/Ketone Meter Testing blood ketones with FreeStyle Optium and FreeStyle Optium Neo Testing urine ketones Measures β-hydroxybutyrate - the predominant blood ketone Direct measurement of ketones in the circulation Indicates current ketone levels, allowing prompt action Measures acetoacetate - a poor indicator of overall blood ketone levels Indirect measurement of ketones in the circulation Indicates level of ketones in blood 2-4 hours previously Advanced biosensor technology minimises interference from common drugs Unaffected by levels of fluid intake (unless severely dehydrated) Accuracy protected by individually foil wrapped test strips False positive results with captopril. False negative results with high levels of vitamin C High fluid intake may dilute urine leading to false negatives. Low fluid intake or dehydration may lead to false positives Infrequently used test strips exposed to air degrade over time

36

37 Source: Seyfried: Cancer as a Metabolic Disease 13 Seyfried, T. N., Kiebish, M. A, Marsh, J., et al (2011). Metabolic management of brain cancer. Biochimica et Biophysica Acta, 1807(6), (but reproduced from 2008 paper)

38 Ketogenic Diet Secret weapons 2. Spiraliser

39 Red Pesto Courgetti

40 Sesame Chicken Salad w/ Cucumber Noodles

41 Low Carb Vegetables (less than 6g/cup) Alga (nori, kombu, wakame) Daikon Redish Salads all types Artichoke Eggplant Sauerkraut Avocado Endive Savoy Cabbage Asparagus Fennel Scallions Bamboo Shoots Green Beans Sheet Rope Bean Sprouts Gherkin (pickled*) Sprouts (alfalfa, clover, radish) Beet Greens Herbs & Spices Sorrel Bok Choy Jicama (Mex. Yam) Spinach Broccoli Kale Snow Peas Brussel Sprouts Mushrooms Summer Squash Cabbage (Chinese, Green etc.) Napa Cabbage Taro leaves Cauliflower Okra Tomatoes* Celery Olives Turnips Celery Root/Cerliac Kohlrabi Water Chestnuts Chard Peppers (hot & sweet) Watercress Chives Radish Wax Beens Collard Greens Rhubarb Zucchini Cucumber Rocket * not for patients with a histamine intolerance Medium Carb Vegetables (between 7-14 g/cup)* Beets Carrots Leeks Onion

42 Low Carb Fruits* Blackberries Boysenberries Cowberries Damson Plum Gooseberries Grapefruit Red current * additional fruits see table with glycemic load Raspberries Huckleberries Lemons Lime Low Carb Nuts Cave: do not it nuts with histamine intolerance! Almond English Walnuts Black Walnut Hazelnuts Brazil Nuts Macadamia Coconut Pecan 3

43 Ketogenic Diet Secret weapons 3. MAP

44 Master Amino Acid Pattern Patent no US A; 4. A nutritional composition as defined in claim 1 which comprises in grams per 10 grams of composition: (a) from to isoleucine; (b) from to leucine; (c) from to lysine; (d) form to methionine; (e) from to phenylalanine; (f) from to threonine; (g) from to tryptophan; and (h) from to valine.

45 Nitrogen Utilisation 147

46 Nutritional state Ketone level mmol/l Moderate Carb diet (not in fasting state) <0,1 Moderate Carb diet (fasting state) 0,1-0,3 Fasting or starvation ketosis 5,0-8,0 Very low carb (<50g/Tag) Nutritional Ketosis Very low carb with MAP Nutritional Ketosis + managing cancer growth 0,5-3,0 1,0-8,0 Ketoazidosis (Typ 1 Diabetes) 10,0-25,0 150

47

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