Starving Cancer using Ketogenic Diet

By: Jamie LuuSodexo Dietetic Intern 2013®

Personal Intent

Personal Intent

Personal Intent

Personal Intent

Objectives

• Name three areas that the ketogenic diet has been applied• Explain the metabolic difference between brain cancer cells and

normal brain cells• State one way this information can be helpful and used in our

current or future practice

Epilepsy Treatment using Ketogenic Diet

• Effective treatment for refractory seizures in children

Weight Management using Ketogenic Diet

• AKA Modified Atkin’s Diet• Strict low-carb diet to achieve optimal ketosis• Optical ketosis for maximum weight loss - 1.5 - 3 mmol/L• Keeps insulin levels low, puts your body in fat-release-fat-burn mode

and teaches your body (liver) to use ketone bodies as energy by breaking down fat into fatty acids and ketone bodies.

Diabetes Type 2 Treatment using Ketogenic Diet

• Improve glycemic control • Decrease in HbA1c • Decrease in medication usage• Patients must be closely monitored

• Yancy, Wiliiam et al. A low-carbhydrate, ketogenic diet to treat Type 2 Diabetes. Nutrition and Metabolism (2005) 2:34. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1325029/

• Poplawski MM, Mastaitis JW, Isoda F, Grosjean F, Zheng F, et al. (2011) Reversal of Diabetic Nephropathy by a Ketogenic Diet. PLoS ONE 6(4): e18604. doi:10.1371/journal.pone.0018604 http://www.plosone.org/article/info:doi/10.1371/journal.pone.0018604

Cancer is a Mitochondrial Metabolic Disease

• Mitochondria• Power house of the cell • Central point in the origin of

most cancers• Can be damaged by:

• Inherited mutations, increasing your risk for breast- and ovarian cancer

• Environmental factors, toxins and radiation, leading to dysfunction and tumor formation

Sugar is the Primary Fuel for most cancers

• 1931, Nobel Prize awarded to Dr. Otto Warburg, who discovered that cancer cells have a fundamentally different energy metabolism compared to healthy cells, and that malignant tumors tend to feed on sugar.

• Confirmed by: Dr. Thomas Seyfried, one of the leading pioneer academic researchers in promoting how to treat cancer nutritionally at Yale University and Boston College and has written over 150 peer-reviewed scientific articles relating to cancer treatment.

Ketogenic Diet

• An elegant, non-toxic way to target and marginalize tumor cells• Allows you to dramatically lower your glucose levels, as the ketones

will protect your body against any hypoglycemia that might otherwise be induced by carb restriction

• New state of metabolic homeostasis: a state where ketones reach the steady state level in your blood and glucose reach a steady level in your blood

• “If it’s done right and implemented right, it has powerful therapeutic benefits on the majority of people who suffer from various kinds of cancers. Because of all cancers have primarily the same metabolic defect.” - Dr. Seyfried

Ketogenic Diet

• Low amounts of carbohydrates• Eliminating all but non-starchy vegetable carbohydrates

• High amounts of healthy fats• MCTs - avocado, coconut oil, butter, olive oil and macadamia nuts

• Low to moderate amounts of high quality protein

Ketogenic Diet

• Reverse Glucose to Ketone Ratios• Glucose - 55-65 mg/dL (half “normal” level)• Ketones - 3-4 mm/dL (millimolar)

• Measure glucose and ketone blood levels• Glucose, 3x day• Ketones, every few days

• Adverse side affects can occur with medications

Body’s New physiology

• Purpose: Evaluate the efficacy of KetoCal®, a new nutritionally balanced high fat/low carbohydrate ketogenic diet for children with epilepsy, on the growth of vascularity of a malignant mouse astrocytoma (CT-2A) and human malignant glioma (U87-MG)

• Methods: Animal study. KetoCal® administered to groups of mice either in calorie restricted or unrestricted amounts. Tumor growth, vascularity, and mouse survival were examined and compared between two diets.

• Results: KetoCal® administered in restricted amounts significantly decreased tumor growth in both groups by 35-65% and enhanced health and survival rate compared to control group (received standard low fat/high cho diet). Tumor microvessel density was less in KetoCal® compared to calorically unrestricted groups. Less gene expression for mitochondrial enzymes in tumors than normal brain cells - reduced ability to metabolize ketone bodies for energy.

• Zhou et al. The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer. Nutrition and Metabolism 2007, 4:5.

Research Studies1

Research Studies

• Background: Tumor cells, decrease expression of SCOT, key enzyme in ketone body metabolism, therefore cannot use ketone bodies as a primary source of energy.

• Purpose: Examine viability of neuroblastoma cells when using ketone bodies at its primary energy source

• Methods: In Vitro method. Human foreskin fibroblasts (control group) grown in standard media with/out glucose and glucose-free media with ketone bodies, acetoacetate or B-hydroxybutyrate vs. Human Neuroblastoma cells.

• Skinner, R. et al. Ketone bodies inhibit the viability of human neuroblastoma cells. Journal of Pediatric: Surgery (2009) 44. 212-216.

2

• Analysis: MTT assay - determine cell viability; Fluorescence-activated cell sorting analysis - determine apoptosis; Immunoblotting for SCOT protein expression.

• Results: Viability and apoptosis, not affected in normal fibroblasts compared to neuroblastoma cells - 52%-61% significantly less viable and more apoptosis. SCOT protein was significantly less in neuroblastoma cells vs fibroblast cells.

• Skinner, R. et al. Ketone bodies inhibit the viability of human neuroblastoma cells. Journal of Pediatric: Surgery (2009) 44. 212-216.

Research Studies2

• Purpose: Investigate the feasibility of a KD and its influence on the quality of patients with advanced metastatic cancer.

• Methods: 3 month intervention, patients followed a KD (less than 70 g CHO per day) with protein/fat shakes.

• Analysis: Quality of life, serum and general health parameters at baseline, two-week follow-up, or after drop out. Monitor effect of dietary change on metabolism daily by measuring urinary ketone bodies

• Results: 5 patients completed intervention, showed improved emotional functioning, less insomnia. Found no severe adverse side effects and no changes in cholesterol or blood levels.

• Schmidt et al. Effects of a ketogenic diet on the quality of life in 16 patients with advanced cancer: A pilot trial. Nutrition and Metabolism 2011, 8:54.

Research Studies3

Comparative Findings

• Tumor cells cannot use ketone bodies because of their respiratory insufficiency and decrease expression of SCOT protein (enzyme).

• Therapeutic effect of KetoCal® for brain cancer was largely due to caloric content, which reduces circulating glucose.

• It’s possible to target brain cancers with calorically restricted high fat/low carbohydrate ketogenic diets.

• KD suitable for even advanced cancer patients. KetoCal® is safe

effective diet therapy and should be considered an alternative therapeutic option for malignant brain cancer.

• No severe adverse side effects.• Might improve aspects of quality of life and blood parameters

in some patients with advanced metastatic tumors.

More findings needed...

Dietetic Clinical Application

• Nutrition Assessment• Diet Intervention

• Ketogenic Diet• Calorically-restricted

• Monitoring and Evaluation• Counseling• Labs: Ketone Bodies and Glucose Monitoring

Thank you!