Phytochemicals Nutritional Support in the Present Environment

Phytochemicals: Nutritional Support in the Present Environment K. W. Chang, Ph.D. Amway Korea, Ltd. Determinants of Health and Wellness • Uncontrollable – Genetic factors – Environmental factors • infectious agents, • pollution, • xenobiotics • Controllable – – – – Diet Physical activity Rest Stress coping; positive outlook A Balanced Diet • Macronutrients – carbohydrates – proteins – fats • Micronutrients – vitamins – minerals • Phytonutrients – carotenoids – flavonoids – etc. Phytochemicals • Antioxidants – flavonoids, carotenoids • Detoxification agents – glucosinolates, isothiocyanates • Synergize with vitamins – bioflavonoids • Reduce risk of chronic disease Fruit and Vegetable-Rich Diets: Phytochemicals versus Phytonutrients • Phytochemical: any naturally occurring substance present in plants • Phytonutrient: a non-nutritive, yet biologically-active and beneficial substance present in plants What are Phytonutrients? • Phyto = plant • Nutrient = nourishment • Protect against disease to promote good health. • Antioxidants – protect against cellular damage. • Different plants have different phytonutrients. Age-Related Degenerative Disease is Prevalent Ar thr itis Osteopenia Hy per tension CHD Ca ta r a ct Dia betes COPD Str oke Dementia Ca ncer 0 10 20 30 40 50 60 % of Population Over Age 65 Source: Health, United States, 1999 With Health and Aging Chartbook, National Center for Health Statistics Age-Related Degenerative Disease is Rising Arthritis Hypertension CHD Cancer Diabetes Stroke 0 10 20 30 40 50 60 1984 1995 % of Adults Over 70 Source: Older Americans 2000: Key Indicators of Well-Being, Federal Interagency Forum on Aging Related Statistics, www.agingstats.gov Cause of death in China (1970’s vs 1990’s):male • Respiratory 23.9->23.1% • M. Neoplasms 13.8->18.8% • Cerebro-vascular 11.0>17.4% • Digestive 9.0->5.1% • Injury/poison 8.1->9.5% • Heart disease 7.1->8.1% “Epidemiologic data support the association between HIGH intake of vegetables and fruits and LOW risk of chronic disease.” Lampe, Am J Clin Nutr 1999; 70: 475S-490S. “Risk for coronary heart disease can be reduced 20% to 40% by Fruit & Vegetable intake.” Fruits and Vegetables in Chronic Disease Prevention Klerk M et al 1998 Grafisch Bedrijf Ponsen & Looijen BV, Wageningen, The Netherlands Phytonutrient-Rich Diets Reduce Risk for Age-Related Degenerative Disease • Strong Evidence – – – – – – Cancer CHD Stroke Hypertension COPD Cataract • Emerging Evidence – Diabetes – Osteopenia • Preliminary Evidence – ARMD – Arthritis – Alzheimer's Disease Multiple Phytonutrient Classes are Associated with Risk Reduction for Chronic Disease b-Carotene Allyl sulfides Coronary Heart Disease Vitamin E Folic Acid, B Vitamins Polyphenols Anthocyanins Vitamin C Phytonutrients Impact Chronic Disease via Multiple Mechanisms Improved vascular compliance Improved lipoprotein profile Improved vascular reactivity Coronary Heart Disease LDL oxidation protection Decreased platelet aggregation Reduced homocysteine Reduced lipid peroxidation Reduced blood pressure Phytochemical Mechanisms for Reducing Disease Risk • Antioxidant • Anti-inflammatory • Modulation of detoxification mechanisms • Inhibition of cancer initiation, promotion Lampe JW 1999 Am J Clin Nutr 70:475S-490S Nijveldt RJ et al 2000 Am J Clin Nutr 74:418-425 Watson RR 2001 Vegetables, Fruits and Herbs in Health Promotion. CRC Press Age-Related Degenerative Disease Associated with Oxidant Stress • Atherosclerosis; myocardial infarction, stroke, thrombosis • Selected cancers • Cataracts, macular degeneration • Alzheimer's disease • COPD • Diabetes Phytochemicals & Antioxidants • Many phytochemicals are antioxidants • Antioxidants inactivate free radicals • Antioxidants help to reduce damage to cells, lipids and DNA • A mixture of antioxidants is thought to offer the most health benefit • Fruits and vegetables are excellent sources of antioxidants. Physiology and Pathology of Reactive Oxygen Species Antioxidant Phytonutrients Finkel T et al 2000 Oxidants, oxidative stress and the biology of aging. Nature 408:239-247 Ames BN et al 1993 Oxidants, and the degenerative diseases of aging. Proc Natl Acad Sci USA 90:7915-7922 Phytonutrients Interfere with Inflammation via Multiple Mechanisms • Antioxidant Activity – Inhibition of inflammatory ROS catalyzed lipid peroxides • vitamins C, E, rutin, quercetin, catechins, anthocyanins – Inhibition of high Nitric Oxide levels from inducible Nitric Oxide Synthase • quercetin • Inhibition of Inflammatory Signaling Cascade – Inhibition of NFkB activation, inhibiting cyclooxygenase-2 expression, and production of inflammatory prostaglandins • curcuminoids, resveratrol, catechins Metabolic Activation and Detoxification Pathways Phase I Reactions • oxidation • hydroxylation • reduction • dehalgoenation drugs, steroid hormones, chemicals, toxins Cytochrome P450 enzymes Intermediates Damage to DNA, proteins, lipids Sulfotransferases UDP-glucuronosyltransferases Glutathione S-transferases Acetyltransferases Detoxified, conjugated products Phase II Reactions • sulfation • glucuronidation • acetylation • amino acid conjugation • methylation Excretion Diet Effects on Metabolic Activation and Detoxification Phase I Reactions • cruciferates Phase I Reactions • grapefruit drugs, steroid hormones, chemicals, toxins Cytochrome P450 enzymes Intermediates Phase II Reactions • cruciferates • Allium sp Damage to DNA, proteins, lipids Sulfotransferases UDP-glucuronosyltransferases Glutathione S-transferases Acetyltransferases Detoxified, conjugated products Excretion Detoxification Enzymes and Diet Human Experimental Studies • Increased glutathione S-transferase activity – Brussels sprouts : Nijhoff et al, 1995 – Broccoli : Sreerama et al, 1995 • Increased glucuronidation – Brussels sprouts & cabbage : Pantuck et al, 1984 – Watercress : Chen et al, 1996 • Altered metabolism of NNK (Tobacco carcinogen) – Watercress : Hecht et al, 1995 Lampe JW 1999 Am J Clin Nutr 70:475S-490S Fruits and Vegetables and Carcinogenesis • Epidemiologic research shows that plant-based diets are associated with a decreased incidence of cancer • Overall dietary patterns, rather than specific individual compounds, are most strongly linked Lampe JW 1999 Am J Clin Nutr 70:475S-490S A Model of Carcinogenesis Normal Cell Cell with DNA Abnormality Tumor MUTATION Inherited Spontaneous Acquired PROMOTION PROGRESSION Initiation Promotion Lampe JW 1999 Am J Clin Nutr 70:475S-490S Impact of Environmental, Lifestyle, and Dietary Factors on Carcinogenesis Smoking and other exposures DNA repair genes Procarcinogen Lesions/Dysplasia DNA damage Immune system Dietary factors Growth factors Hormones DNA damage CANCER Smoking and other exposures Metastasis DNA repair genes Disability from Degenerative Disease: A Major Cause of Age-Related Health Decline CHD Optimum Health Health hypertension COPD stroke Poor Health Chronic Degenerative Disease cancer Life Span Lifestyle Factors Promoting Healthy Aging The longer the healthy lifestyle, the greater the impact. Optimum Health Fruit & Vegetable-Rich Diet Physical Activity Low Risk Behavior Poor Health Healthy Lifestyle Life Span Carl Rehnborg : Nutrilite Health Institute -1934 Plant Concentrates Fiber Acerola Carrots Alfalfa Water Nutrients in Alfalfa Carotenoids Nutrients in Acerola Synthetic Vitamin C Acerola Lycopene • High tomato consumption decreases risk of prostate cancer 35% • Epidemiological studies suggest protective effect against stomach and lung cancer Lutein • Reduces risk of Age-Related Macular Degeneration (ARMD) 43% • Reduces risk of colon cancer 17% Source: Seddon JM, et al. JAMA. 1994;272:1413-1420 Am J Clin Nutr, Feb 1, 2000;71:575-582 Lutein and Age-Related Macular Degeneration Yellow and dark green leafy vegetables lutein Decreased lutein is associated with increased risk for age-related macular degeneration Flavonoids Quercetin, resveratrol, catechins, hesperidin • Men with highest intake of flavonoids decrease risk of dying from heart disease by 50% Source: Hertog MGL, et al. Lancet. 1993;342:1007-11. Resveratrol • Believed to be responsible for the ‘French Paradox’ • Cardioprotective functions – Inhibits LDL oxidation – Regulates heart rhythm – Reduces platelet aggregation Catechins Catechins in green tea > black tea. • EGCG=epigallocatechin gallate • Best source is green tea • Reduce risk of cancer • Protects against heart disease, atherosclerosis • 7-10 cups/day Source: Biofactors 2000; 13: 49-54. Hesperidin • In combination with another citrus bioflavonoid (diosmin), improves venous tone and elasticity. • May reduce cancer cell proliferation. • May improve serum lipid levels. Garlic • Reduces blood cholesterol by 9-12%. • Lowers blood pressure by 5-10% more than placebo. • High garlic consumption decreases risk of colon cancer by 30 %. Source:Ann Intern Med 1995; 119: 599-605. J Hypertens 1994; 12: 463-468. Isoflavones • Decrease risk of breast cancer in pre-menopausal women • Protect against bone loss in post-menopausal women Source: Anderson et al., N Engl J Med1995 Am J Clin Nutr 1999; 70: 439S-450S. Glucosinolates and Isothiocyanates Broccoli, cabbage, Brussels sprouts, kale, cauliflower • Phytochemicals activate detoxification system in the liver to reduce cancer risk. • Most protective against lung, stomach, colon and rectal cancer. Source: Adv Exp Med Biol 1999; 472: 159-168. Benefits of Fruits & Vegetables • Spinach • Tomatoes • Oranges • Grapes/wine lutein lycopene hesperidin resveratrol eyes heart, prostate cardiovascular cardiovascular • Green tea • Soy • Broccoli etc catechins isoflavones sulforophanes heart, cancer breast, bone detoxification • Berries (blue) • Berries (red) anthocyanins ellagic acid cardiovascular DNA structure Scientific support Thank You !