Antioxidants and Alternative Therapies for Cancer: Antioxidants and Alternative Therapies for Cancer Primary Prevention, Integrative Treatment, or Last Ditch Effort?


Victor S. Sierpina, MD: Victor S. Sierpina, MD Associate Professor/Family Medicine Principle Investigator “Evidence- Based Curriculum in Alternative Therapies” (funded by NIH/NCCAM)


Anti-oxidants and CancerTHE SHORT COURSE: Anti-oxidants and Cancer THE SHORT COURSE Eat your vegetables! Drink green tea and red wine! Evidence for anti-oxidant supplements is less than robust Anti-oxidants need to be evaluated during chemotherapy


“I have seen no decisive and scientifically documented cure for any type of cancer among the complementary cancer therapies” : “I have seen no decisive and scientifically documented cure for any type of cancer among the complementary cancer therapies” Michael Lerner, Author, Choices in Healing, 1994


Healing or Curing?: Healing or Curing? Healing results in integration, meaning An inner process through which a person becomes whole Emotional, mental, spiritual dimensions Quality of life Curing is elimination of the disease state A successful medical treatment What the doctor hopes to do


Vital Quartet: Vital Quartet Spiritual Psychological Physical Nutritional


Spiritual: Spiritual Prayer Faith Healing Meaning Community/Religious Practice Spirituality


Psychological: Psychological Psychoneuroimmunology Psycho-oncology Stress reduction and management Social and group support Imagery Personality, “fight for life”


Physical: Physical Exercise Massage Therapeutic Touch Chiropractic


Additional Options: Additional Options Traditional medicine Pharmacological Herbal Electromagnetic Unconventional use of conventional tx Esoteric & Psychic Unconventional instruments, apparatuses, and diagnostic tests Humane, patient-centered approaches


Nutritional: Nutritional Prevention through diet Supportive dietary programs Supplements and micronutrients Unconventional diets for treatment


Types of Anti-Oxidants: Types of Anti-Oxidants Cellular enzymes Glutathione reductase (Se) Superoxide dismutase (Zn, Mg, Cu) Metal Ion Chelators Albumin, ceruloplasmin, transferrin, haptoglobin, metallothionein Small molecules Vitamin C & E, uric acid, bilirubin (chain-breaking antioxidants)


Antioxidants: Antioxidants Green leafy and cruciferous vegetables Black and green tea Carrots Citrus Grapes/Resveratrol (red wine)


Antioxidants: Antioxidants Vitamins A, C, and E Beta-carotene Bioflavonoids CoEnzyme Q10 Selenium


Anti-oxidants: Anti-oxidants Oxidant by-products of normal metabolism result in extensive damage to DNA, proteins and lipids, leading to aging and degenerative diseases including cancer, cardiovascular disease, immunoincompetence, brain dysfunction and cataracts.* Low intakes of fruits and vegetables double the risk of many types of cancer versus high intakes. *Proc NY. Acad Sci. 1993; 90: 7915-7922


Actions of Anti-Oxidants: Actions of Anti-Oxidants Reduction of free radicals Hydrogen Peroxide H202 Hydroxyl Radical OH- Superoxide Radical O2-


Biochemical Functions of Anti-Oxidants : Biochemical Functions of Anti-Oxidants


Actions of Anti-Oxidants: Actions of Anti-Oxidants Genetic modification Limonene (grapefruit) induces glutathione S-transferase Soy affects enzyme that converts testosterone to 5 DHT Cruciferous vegetables help detoxify cancer causing chemicals through induction of glutathione s-transferase and other enzymes


Evidence against Anti-oxidants in Cancer Prevention: Evidence against Anti-oxidants in Cancer Prevention CARET and Finnish trials showed Vit A/Beta Carotene increased risk of lung cancer in smokers* Possibly smokers metabolize synthetic vs natural beta-carotene differently * NCI CARET: Omenn GS, et al. NEJM 1996; 334:1150-1155 * Finnish ATBC trial: Heinonen OP, Albanes D NEJM 1994;339:1029-1035


Evidence against Anti-oxidants in Cancer Prevention: Evidence against Anti-oxidants in Cancer Prevention Recent systematic cohort analysis of nearly 300,000 women found no protective benefit against breast cancer by women in the highest quartile of fruit and vegetable consumption vs. those in the lowest quartile.* ** JAMA


Evidence for antioxidants in Cancer Prevention- Tomatoes and Selenium: Evidence for antioxidants in Cancer Prevention- Tomatoes and Selenium Reduction of prostate cancer by lycopene in tomato products* Reduction of esophageal cancer in Chinese patients given Selenium (generalizability?) *Giovannucci E, Clinton S. “Tomatoes, Lycopene, and Prostate Cancer.” Prostate Cancer 1998: 129—139.


Evidence for antioxidants in Cancer Prevention-- Green tea : Evidence for antioxidants in Cancer Prevention-- Green tea Has catechins, epigallocatechins, polyphenols which act as anti-oxidants. Lower rates of lung cancer among Japanese men who smoke but drink green tea Increased tissue levels of doxorubicin 2.5X in tumor but not healthy tissue* *Sadzuka. Modulation of Cancer Chemotherapy by Green Tea. Clin Can Res. 1998;4:153-156


Evidence for antioxidants in Cancer Prevention--Foods**: Evidence for antioxidants in Cancer Prevention--Foods** Reduction of colon and other cancers with cruciferous vegetables (see TABLE in handouts) Dark leafy green vegetables Fruits/nuts/legumes Soy Garlic Omega-3 fatty acids; fish, green vegetables **Werbach M. Nutritional Influences on Illness, A Sourcebook of Clinical Research. Tarzana, CA: Third Line Press, 1996.


Anti-oxidants and Cancer Treatment: Anti-oxidants and Cancer Treatment Case studies (Willis, Folkers) indicate CoQ10 may be helpful in prolonging survival in breast cancer patients* Melatonin has been found in several studies (Lissoni) to promote responses to chemotherapy in tumors of brain, lung, melanoma** * Gordon p 153 ** Gordon p 155


Anti-Oxidants and Chemotherapy: the Controversy: Anti-Oxidants and Chemotherapy: the Controversy Anti-oxidants lower the side effects of chemotherapy by reduced oxidative species increasing compliance with treatment, quality of life May lower effectiveness of chemotherapy that depends on such species for tumor destruction (See handout articles by Labriola. Oncology, July 1999 and Austin, Health Notes Review, Winter 1999)


Anti-Oxidants and Chemotherapy: the Controversy. Things to Consider: Anti-Oxidants and Chemotherapy: the Controversy. Things to Consider Fraction of drug effectiveness dependent on reactive oxygen species Nature of the reactive species Dosage and concentration of reactive species Nature of anti-oxidant Concentration of anti-oxidant Temporal relationship in dosing


Anti-Oxidants and Chemotherapy: the Controversy. Toxicity: Anti-Oxidants and Chemotherapy: the Controversy. Toxicity When anti-oxidants were used prior to tx, animal models showed decreased cardiotoxicity of Adriamycin , nephrotoxicity and ototoxicity from Cis-Platinum, pulmonary toxicity of Bleomycin Few convincing human clinical trials *Weijl N et al. Free Radicals and antioxidants in chemotherapy-induced toxicity. Canc Treat Reviews(Saunders) 1997;23:209-240


References: References Gordon JS, Curtin S. Comprehensive Cancer Care:Integrating Alternative, Complementary, and Conventional Therapies. Perseus: NY; 2000. (based on international Comprehensive Cancer Care conferences co-sponsored by the Center for Mind-Body Medicine, the National Cancer Institutes, and the NIH National Center for Complementary and Alternative Medicine)


References: References Lerner, M. Choices in Healing. Cambridge, MA: MIT Press, 1994 Spencer, JW, Jacobs, JJ. Complementary/Alternative Medicine--An Evidence-Based Approach. St. Louis, MO: Mosby, 1999


References: References Wirth, S. Integrative Medicine--A Balanced Account of the Data. Ukiah, CA: Boitumelo Press, 1999 Watkins, A . Mind-Body Medicine--A Clinician’s Guide to Psychoneuroimmunology. New York, NY: Churchill Livingstone, 1997


Integrative Healthcare: Complementary and Alternative Therapies for the Whole Person: Integrative Healthcare: Complementary and Alternative Therapies for the Whole Person By: Victor S. Sierpina, MD FA Davis Philadelphia, 2001 www.fadavis.com www.amazon.com


Slide37: UTMB’s Alternative and Integrative Health Care Program Website http://atc.utmb.edu/altmed


References: References McKenna, DJ et al. Green tea monograph. Alternative Therapies. May 2000;6(3):61-82 Weijl, NI et al. Free radicals and antioxidants in chemotherapy-induced toxicity. Cancer Treatment Reviews 1997;23:209-240


References: References Nagata, C. et al. Association of coffee, green tea, and caffeine intakes with serum concentrations of estradiol and sex hormone-binding globulin in premenopausal Japanese women. Nutrition and Cancer. 1998;30(1):21-24 Zhang, S. et al. Dietary carotenoids and vitamins A, C, and E and risk of cancer. J of National Cancer Inst. 1999;91(6): 547-556


Reference: Reference Nakachi, K. et al. Influence of drinking green tea on breast cancer malignancy among Japanese patients. Japanese J. Cancer Res. 1998;89:254-261 Ziegler, RG. Vegetables, fruits, and carotenoids, and the risk of cancer. Am J Clin Nutri. 1991;53:251S-9S


Reference: Reference Smith-Warner, SA et al. Intake of fruits and vegetables and risk of breast cancer: A pooled analysis of Cohort studies. JAMA 2001;285(6):769-776 Slattery, ML. Does an apple a day keep breast cancer away? JAMA 2001;285(6):799-801


Reference: Reference Sankaranarayanan R. et al. Retinoid as cancer-preventive agents. In Principles of Chemoprevention. Stewar BW, McGregor D, and Kleihues, P., eds IARC Scientific Publications No. 139 International Agency for Research on Cancer, Lyon, 1996


Reference: Reference Sadzuka, Y. et al. Modulation of cancer chemotherapy by green tea. Clinical Cancer Research. 1998;4:153-156