integrative cancer care - warren ross m.d. 12/11/10

IntegrativeCancer Care : 

IntegrativeCancer Care

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Conventional Medical Model The focus is on early diagnosis for the presence of cancer. Determination of the characteristics of the tumor and cancer cells

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Conventional Medical Model Eradication of the tumor and cancer cells: Surgery, Radiation Therapy Medical Therapies Chemotherapy Hormonal Therapy Biological Agents

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Complimentary Medical Model Understand the Person who has the disease The ‘Terrain’ in which the problem arises The nature or energetics of the person The environment the person operates in The biology of the individual

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Complimentary Medical Model Therapeutic Goals Optimize Nutrition, Assimilation and Elimination Support Detoxification Processes Boost innate host resistance modulate terrain to remove metabolic factors that favor tumor proliferation, progression, angiogenesis, metastasis

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Hallmarks of Cancer self-sufficiency in growth signals! disregard of anti-growth signals! limitless replication (↑telomerase)! evade apoptosis! lack of differentiation! sustained angiogenesis! tissue invasion! metastasis!

Cancer Permissive Factors : 

Cancer Permissive Factors Metabolic Syndrome: ↑glucose, ↑ insulin, ↑ lipids

Cancer Permissive Factors : 

Cancer Permissive Factors Systemic inflammation: ↑CRP, ↑ COX, ↑ 5-LOX, ↑ PGE2!

Cancer Permissive Factors : 

Cancer Permissive Factors Hypercoaguability: ↑fibrinogen, ↑ D-Dimer! Sustained Angiogenesis: ↑f-Cu, ↑ VEGF, ↑ EGF, ↑ PDGF

Cancer Permissive Factors : 

Cancer Permissive Factors Hormone Imbalance: ↑aromatase, ↓ SHBG, ↑ E2

Cancer Permissive Factors : 

Cancer Permissive Factors Hypovitaminosis D: ↓fat-soluble vitamins A, D, K, E, coQ10

Cancer Permissive Factors : 

Cancer Permissive Factors ReDox Imbalance: ↑ROS, ↓ antioxidant intake, gene instability

Cancer Permissive Factors : 

Cancer Permissive Factors Immune Incompetence

Metabolic Syndrome and Cancer : 

Metabolic Syndrome and Cancer Waist-to-Hip Ratio > 0.85 or BMI > 30 Waist Circumference M > 40”, F > 35” Fasting Glucose > 90-110; or 2 hr post prandial glucose > 120-140 Glycated hemoglobin A1c > 5.0-5.2% Triglycerides > 110-150 HDL cholesterol < 50-55 Blood Pressure > 130 systolic, 90 diastolic

Metabolic Syndrome and Cancer : 

Metabolic Syndrome and Cancer People can be normal weight but metabolically obese MONW

Metabolic Syndrome and Cancer : 

Metabolic Syndrome and Cancer Breast Cancer - Risk of recurrence within 5 yrs was 3-fold greater in pts with MetS [Pasanisi et al., 2006] Colorectal Cancer - Rates of tumor recurrence and liver mets higher in patients with MetS [Shen et al., 2010]

Metabolic Syndrome Causes : 

Metabolic Syndrome Causes DIET - excess caloric intake; ↑ refined CHOs and ↑ GI / GL foods ! DIGESTIVE INCOMPETENCE - impaired digestion of proteins andfats yields ↑ post-prandial glycemic spike! SEDENTARY LIFESTYLE - ↓ muscle mass, ↑ adiposity !STRESS - altered diurnal pattern of cortisol secretion, interrupted sleep patterns, dysregulated HPA axis! SMOKING - ↑ ROS! TREATMENT EFFECT - side effect of adjuvant glucocorticoidmedications and chemotherapy [Demark-Wahnefried et al., 2001]! NUTRIENT DEFICIENCIES - vitamin D, magnesium, zinc, chromium!

Causative Factors for Metabolic Syndrome : 

Causative Factors for Metabolic Syndrome Dietary Practices Excess caloric intake Excess intake of refined carbohydrates Excess intake of high Glycemic Index Foods

Causative Factors for Metabolic Syndrome : 

Causative Factors for Metabolic Syndrome DIGESTIVE INCOMPETENCE Inadequate digestion of proteins and fats Results in an excess rise in blood sugar after eating.

Causative Factors for Metabolic Syndrome : 

Causative Factors for Metabolic Syndrome SEDENTARY LIFESTYLE Results in a decrease in muscle mass and an increase in fat; particularly fat within the abdominal cavity

Causative Factors for Metabolic Syndrome : 

Causative Factors for Metabolic Syndrome STRESS Altered diurnal pattern of cortisol secretion Results in Interrupted sleep patterns and Dysregulation of the Hypothalamic Pituitary Adrenal Axis (HPA)

Causative Factors for Metabolic Syndrome : 

Causative Factors for Metabolic Syndrome Toxic Exposures and Toxic Burden Causes an increase in ROS Tobacco, Alcohol and other Drugs Industrial Pollutants Household Products Cosmetics

Causative Factors for Metabolic Syndrome : 

Causative Factors for Metabolic Syndrome TREATMENT EFFECT side effect of adjuvant glucocorticoid medications and chemotherapy [Demark-Wahnefried et al., 2001]

Causative Factors for Metabolic Syndrome : 

Causative Factors for Metabolic Syndrome NUTRIENT DEFICIENCIES vitamin D, magnesium, zinc, chromium SOURCE: Demark-Wahnefried W, et al: Changes in weight, body composition, and factors influencing energy balance among premenopausal breast cancer patients receiving adjuvant chemotherapy. J Clin Oncol, 2001 ! May 1,19(9):2381-9

Diet Strategies to Address Metabolic Syndrome : 

Diet Strategies to Address Metabolic Syndrome Limit starchy carbohydrates to 1-3 servings per day Reduce intake of High Glycemic Index/High Glycemic Load Foods Choose whole grains (e.g., can see the individual grains), preference gluten-free grains Aim for 1 gm fiber per 50-60 kCal/day

Diet Strategies to Address Metabolic Syndrome : 

Diet Strategies to Address Metabolic Syndrome High Glycemic Index Foods Breads, Cereals and Oatmeal, Cracker Muffins, Bagels, Pancakes. White flour Chips, Pretzels, Corn Soft Drinks, Fruit Juice, Dried Fruits; dates/raisins, Bananas Potatoes, Parsnips

Diet Strategies to Address Metabolic Syndrome : 

Diet Strategies to Address Metabolic Syndrome Avoid eating carbohydrate foods alone (combine with protein & healthy fats) Limit caloric beverages: avoid High Fructose Corn Syrup (HFCS) Avoid eating late in the day and evening snacking; reduce evening meal size Reduce caffeine intake

Dietary Supplements to Address Metabolic Syndrome : 

Dietary Supplements to Address Metabolic Syndrome Alpha Lipoic Acid, L-carnitine, Biotin Chromium, Vanadium, Zinc Omega-3 fatty acids, Conjugated linoleic acid American Ginseng, Blueberry Leaf, Bitter Melon, Cinnamon, Gymnema sylvestre Fenugreek seed fiber, Milk Thistle (silymarin) YehGY et al: Systematic review of herbs and dietary supplements for glycemic control in diabetes. Diab Care 2003 Apr;26(4):1277-94. • Kaushik G, et al: Commonly consumed Indian plant food materials in the management of diabetes mellitus. DiabMetabolSyndr: Clin Res Rev, 2008 Mar." doi:10.1016/j.dsx.2008.02.006

Foods to Help Lower Blood Sugar : 

Foods to Help Lower Blood Sugar Fruits: Blueberries, Raspberries, Cherries, Apples with peel, Lemon, Goji berry, Persimmon, Jujube Vegetables: Garlic, Onions, Leeks, Chives, Parsley, Chard, Avocado, Sweet Potato Nuts and Seeds Olive Oil, Apple cider Vinegar Miscellaneous: caraway, Capers, Flaxseed meal, Oat bran, Barley, Fenugreek Beverages: Chamomile tea, Green tea, Stevia, Roman-Ramos R, et al: Anti-hyperglycemic effect of some edible plants. J Ethnopharmacol, Aug 11, 1995;48(1):25.32.!

Typical Supplement Protocol for Metabolic Syndrome : 

Typical Supplement Protocol for Metabolic Syndrome American Ginseng: 450-900 mgs/d Biotin: 4.5-9 mgs/d R-lipoic acid: 600-900 mgs/d L-carnitine: 2.5-5 grams/d Chromium: 500-1,000 mcg/d Vanadium: 250-500 mcg/d Cinnamon: 2,000 mg/day/d Gymnema sylvestre 75%: 100-200 mgs/d Fenugreek: 400-800 mgs/d Holy basil: 400-800 mgs/d Silymarin (milk thistle): 500-1,000 mgs/d

Inflammation and Cancer : 

Inflammation and Cancer Survival of Cancer Patients Correlates to the Level of Inflammation The Greater the Background Inflammation the Shorter the Survival McMillan DC, et al: Measurement of the systemic inflammatory response predicts cancer-specific and non-cancer survival in patients with cancer. Nutr Cancer, 2001;41(1-2):64-9.

Inflammation and Cancer : 

Inflammation and Cancer C reactive protein is an important prognostic marker for long-term survival in cancer patients, independent of race, tumor stage and body mass index. Nozoe T, et al: Preoperative elevation of serum C-reactive protein as an independent prognostic indicator of colorectal carcinoma. Surg Today. 2008;38(7):597-602. Pierce BL: Elevated biomarkers of inflammation are associated with reduced survival among breast cancer patients. J Clin Oncol. 2009 Jul 20;27(21):3437-44.

Inflammation and Cancer : 

Inflammation and Cancer It is not clear that elevated CRP is associated with an increased incidence of cancer, however

Inflammation and Cancer : 

Inflammation and Cancer Circulating C-reactive protein concentrations and risks of colon and rectal cancer: a nested case-control study within the European Prospective Investigation into Cancer and Nutrition These data provide evidence that elevated CRP concentrations are related to a higher risk of colon cancer but not rectal cancer, predominantly among men and independently of obesity, insulin resistance, and dyslipidemia Am J Epidemiol. 2010 Aug 15;172(4):407-18. Epub 2010 Jul 15

Inflammation and CancerOther Findings : 

Inflammation and CancerOther Findings Toxicity of Chemotherapy - Elevated inflammation is associated with more severe low blood counts during chemotherapy [Alexandreet al., 2003] Cachexia - Elevated CRP correlates with weight loss, low appetite and muscle wasting in cancer patients [Mahmoud& Rivera, 2002] Fatigue & ↓ QOL - Elevated CRP correlates with measures of fatigue and poorer quality of life in cancer patients [Scott et al., 2003] Alexandre J, et al: Evaluation of the nutritional and inflammatory status in cancer patients for the risk assessment of severe haematological toxicity following chemotherapy. Ann Oncol, 2003;14:36-41. • Mohmoud FA, Rivera NI:The role of C-reactive protein as a prognostic indicator in advanced cancer. Curr Oncol Rep, May 2002;4(3):250-5. •"Scott HR, et al: A prospective study of the impact of weight loss and the systemic inflammatory response on quality of life in patients with inoperable non-small cell lung cancer. Lung Cancer, Jun 2003;40(3):295-9.

Inflammation and Cancer : 

Inflammation and Cancer Nutritional Factors can Modulate inflammation Alexandre J, et al: Evaluation of the nutritional and inflammatory status in cancer patients for the risk assessment of severe haematological toxicity following chemotherapy. Ann Oncol, 2003;14:36-41. • Mohmoud FA, Rivera NI:The role of C-reactive protein as a prognostic indicator in advanced cancer. Curr Oncol Rep, May 2002;4(3):250-5. •"Scott HR, et al: A prospective study of the impact of weight loss and the systemic inflammatory response on quality of life in patients with inoperable non-small cell lung cancer. Lung Cancer, Jun 2003;40(3):295-9.

Dietary Fats and Inflammation : 

Dietary Fats and Inflammation Omega 6 Fat Sources: Commercially-raised meat, poultry dairy and eggs (yolk), vegetable oils (corn, safflower, soy and others), nuts and seeds Tend to promote production of Pro-Inflammatory compounds which: Foster tumor growth and progression, promote angiogenesis, suppress immune function

Dietary Fats and Inflammation : 

Dietary Fats and Inflammation Omega-3 Fats Sources: Cold-water fish, flax, hempseed oil, grass-fed meat, poultry, dairy and eggs. There are small amounts in canola oil, black walnuts, and leafy greens Tend to promote production of Anti-Inflammatory Compounds which: Inhibit tumor growth, complement radiation therapy and chemotherapy, and inhibit angiogenesis

Nuclear Factor kappa betaNF-kB : 

Nuclear Factor kappa betaNF-kB Considered Cancer “Master Switch” A transcription factor that is activated by carcinogens, oxidative stress, viruses, stress, inflammation, radiation and chemotherapy NF-kB is activated in a wide variety of tumors It signals more than 400 genes involved in proliferation, anti-apoptosis, angiogenesis, invasion and metastasis

Nuclear Factor kappa betaNF-kB : 

Nuclear Factor kappa betaNF-kB Dietary Inhibitors of NFkB Almonds, anise, basil, black pepper, caraway, cardamom, cashews, chili pepper, cinnamon, clove, coriander, cumin, curcumin, fennel, fenugreek, figs, flaxseed, garlic, ginger, gooseberry, holy basil, lemongrass, licorice, mango, mint, mustard seed, nutmeg, onion, oregano, parsley, pecans, pomegranate, prunes, rosemary, saffron, sesame seeds, tamarind, turmeric, walnuts.

Additional Strategies to Help Lower Inflammation : 

Additional Strategies to Help Lower Inflammation Optimize blood sugar control (address Metabolic Syndrome) Reduce excess body fat: adipose cells secrete inflammatory compounds and stimulate CRP production Support adequate sleep Exercises such as Qi gong, Tai chi, Yoga Reduce Stress Exercise and Physical Activity Laughter Oh B, et al: Impact of medical Qigong on quality of life, fatigue, mood and inflammation in cancer patients: a randomized controlled trial. Ann Oncol; Mar 2010:21(3):608-14. You T, et al: Effects of hypocaloric diet and exercise training on inflammation and adipocyte lipolysis in obese postmenopausal women.! Clin Edocrinol Metab, 2004;89(4):1739-46.

Anti Inflammatory Protocol Example : 

Anti Inflammatory Protocol Example InflamAway (Natura): 2-4 capsules 3 times per day Bromelain: 750 mgs (2000 gdu potency) tid Fish Oil: 3-5 grams/day Quercetin with Bromelain 1000-1,500 mgs two to three times per day

Hypercoaguability and Cancer : 

Hypercoaguability and Cancer Cancer cells are capable of producing fibrinogen Macrophage infiltration into tumors yields excess inflammation that can trigger the liver to produce additional fibrinogen Elevated fibrinogen levels leads to Red Blood Cell aggregation in the capillaries, creating hypoxia, (a low oxygen state), Hypoxia stimulates neoangiogenesis Hypoxia may contribute to radioresistance and chemoresistance

Hypercoaguability and Cancer : 

Hypercoaguability and Cancer Tumors use fibrinogen to bind and acquire VEGF and other angiogenic growth factors Elevated fibrinogen correlates to metastasis

Natural Inhibitors of Fibrin : 

Natural Inhibitors of Fibrin Atractylodes macrocephala (Bai zhu) Bromelain (from Ananas comosus) Cayenne (Capsicum annuum) Curcumin (Curcuma longa) Salvia miltiorrhiza (Dan shen) Feverfew (Tanacetum parthenium) Fish oil

Natural Inhibitors of Fibrin : 

Natural Inhibitors of Fibrin Garlic (Allium sativum) Ginkgo (Ginkgo biloba) Lumbrokinase (enzyme complex from earthworm): 20 mg bid – 80 mg tid Magnesium Nattokinase: 300-500 mgs per day Chinese peony Vitamin E (mixed tocopherols and tocotrienols)

Fibrinogen Lowering Protocol : 

Fibrinogen Lowering Protocol Bromelain: 750 mgs (potency 2,400 gdu) tid InflamAway (Natura): 2 capsules three times per day Beyond Essential Fats (Natura): 2 tsp per day Pycnogenol 100 mgs bid Nattokinase: 300-600 mgs bid

Copper and Angiogenesis : 

Copper and Angiogenesis Copper increases proliferation and migration of endothelial cells Key pro-angiogenic compounds require copper for their synthesis and activation Hypoxia-inducible factor (HIF-1) Vascular endothelial growth factor (VEGF) Basic fibroblastic growth factor (bFGF) Tumor necrosis factor alpha (TNF-a) Interleukin-1 and angiogenin Lowndes SA & Harris AL:The role of copper in tumour angiogenesis. J Mammary Gland BiolNeoplasia, 2005 Oct; 10(4):299-310. •” NasulewiczA et al: Role of copper in tumor angiogenesis—clinical implications. J Trace Elem Med Biol, 2004;18 (1):1-8. • Harris ED: A requirement for copper in angiogenesis. Nutr Rev, 2004 Feb; 62(2):60-4.!

Angiogenesis, Copper and Cancer : 

Angiogenesis, Copper and Cancer Angiogenesis is the development of a new network of blood vessels which can support tumor growth and invasion. It can be stimulated by: Hypoxia (HIF-1) Pro-angiogenic compounds; VEGF, PDGF, EGF, bFGF Without Angiogenesis tumors remain small and dormant

Copper Levels and Cancer : 

Copper Levels and Cancer Cancer patients have increased serum levels (or Copper:Zinc ratio) compared to healthy controls Serum Copper correlates with tumor burden, advanced disease and poor survival Copper levels rise during active disease and fall to normal levels in remission Clinical trials of copper chelation suggest benefit in disease stabilization

Factors that Contribute to Elevated Copper : 

Factors that Contribute to Elevated Copper Copper plumbing, unfiltered tap water Copper cookware Swimming pool fungicides Medications: oral contraceptives, HRT, tamoxifen, cimetidine, anti seizure meds Dietary supplements (multivitamins with copper, chlorophyll, glandulars) Adrenal hypofunction Zinc Deficiency Cadmium toxicity Estrogen dominance Chronic inflammation

Factors that Contribute to Elevated Copper : 

Factors that Contribute to Elevated Copper FOOD SOURCES Liver, Veal 15 mg/serving Pate 15 Liver, Beef 10 Sesame seeds 8 Oyster 8 Spirulina 6 Soy flour 5 Shitake dried 5 Cocoa pwdr 4 Cashews 2

Copper Chelation : 

Copper Chelation Molybdenum Side effects: impairment of normal wound healing, adverse effects on pregnancy, potential impairment of heart healing and repair. Gout Iron overload Reduced white cell count Anemia

Copper Chelation : 

Copper Chelation Zinc Side effects: Nausea Potential for interference with antibiotics if taken together Possible genitourinary side effects (UTI)

Anti-Angiogenic Foods and Nutrients : 

Anti-Angiogenic Foods and Nutrients VEGF Inhibitors Grape seed Extract Baikal (skullcap) Inositol hexaphosphate Berries Luteolin Boswellia Milk thistle Curcumin Resveratrol Ellagic acid Selenium Fish oil Soy genistein Green tea EGCG

Anti-Angiogenic Foods and Nutrients : 

Anti-Angiogenic Foods and Nutrients EGFR Inhibitors PDGF Inhibitors Reduction of Insulin apigenin Reduction of IGF-1 ellagic acid Green Tea (EGCG) Green tea (EGCG) Grape Seed Extract ginkgo biloba Licorice Resveratrol Quercetin Resveratrol Vitamin D3

Example Copper Lowering Protocol : 

Example Copper Lowering Protocol Adaptogens: 2 capsules Chlorella 400-800 mgs DIM 300 mgs Calcium D-glucarate 1,500 mgs Molybdenum 800-1000 mcg at bedtime Manganese 4-10 mgs MSM 5-7 grams Vitamin C 1-3 grams Zinc sulfate 50-150 mgs

Vitamin D and Cancer : 

Vitamin D and Cancer Mechanisms of Action Induces differentiation Inhibits cell cycle Promotes apoptosis Inhibits invasion, angiogenesis and metastasis in animal models of cancer

Vitamin D and Cancer : 

Vitamin D and Cancer Mechanisms of Action Inhibits Estradiol synthesis and signaling (decreases expression of aromatase, down regulates expression of ER-alpha) Anti-inflammatory (decreases COX-2 expression and PGE2) Plays a role in blood sugar regulation, improves insulin sensitivity

Vitamin D and Cancer : 

Vitamin D and Cancer Breast Cancers - prospective cohort study, 512 pts; early BrCa, 11.6 yr f/u; vit D deficiency assoc. with ↑ risk of recurrence & death [Goodwin et al., 2010] Colorectal Cancer - prospective evaluation, 304 pts; high pre-Dx vitamin D3 assoc. with significant ↑ survival [Ng et al., 2008] Prostate Cancer - 42 pts treated with vit D3 400 - 5,000 iu), 30% response rate (50+% ↓ PSA x median 4 months) [Waxman, 2010] !

Vitamin D and Cancer : 

Vitamin D and Cancer Target Range: 60-80 ng/dl Dose Range to Achieve this goal: 2,000-10,000 IU per day

Smoothie Recipe : 

Smoothie Recipe 8 ounces juice (mango, peach, apricot, etc) 8 ounces water 6 ounces of plain yogurt (goat, cow) 1-2 scoops Beyond Whey (Natura) 1 scoop Nano Greens 1 scoop Yerba Prima Psyllium 1 tsp Immucare I, and or Immucare II (Natura) 1 tsp Botanical Treasures (Natura) 1 tsp Beyond Essential Oils (Natura) 1 tsp Fruit Anthocyanins Syrup

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The Goal Recognize the factors that favor cancer initiation, development and spread Support our patients in minimizing these factors through conventional medical therapy, diet, nutritional supplementation, herbal therapies, exercise and stress reduction therapies Support early detection of cancer through appropriate screening Facilitate access to the best conventional and supportive resources

Acknowledgment and Resources : 

Acknowledgment and Resources

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Jeanne M. Wallace, PhD, CNC Nutritional Solutions Consulting Group 1697 East 3450 North! North Logan UT 84341 Phone: (435) 563-0053 www.nutritional-solutions.net

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The Mederi Foundation 127 Clear Creek Dr. Ashland, OR 97520 Phone: (541) 488-0514 Email address: info@mederifoundation.org Centre for Natural Healing 180 Clear Creek Dr. Suite #101 Ashland, OR 97520 Phone: (541) 488-Email: cnhw@centrehealing.com