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Anticarcinogenic compounds in food Non-nutritive ingredients: phytochemicals Objectives What are phytochemicals? Where are they found? What are the health benefits? Are there any risks? What are functional foods and how are they regulated? What do we tell consumers? Definition of Phytochemicals Biologically active chemical compounds found in plants Not nutrients like vitamins or minerals Believed to have health benefits especially related to heart disease and cancer How Scientists View Phytochemicals in Foods Some phytochemicals have profound effects on the body through actions such as Acting as antioxidants Mimicking hormones Altering blood constituents in ways that may protect against some diseases Mechanisms of Chemoprevention Antioxidants: defense against radicals Phase 1 enzyme inducers Phase 2 enzyme inducers Anti-proliferative agents Anti-hormonal compounds Disruption of mutational gain or loss of function Is More Better? Choose Food First Avoid Overdosing Avoid Self Prescribing Berries (sources of vitamin C, E, carotinoids, flavonoids, phytoestrogenes and other phytochemicals) cloudberry cranberries blackberry blackthorn raspberry gooseberry dogberry huckleberry loganberry blueberry strawberry redcurrant blackcurrant Spices and cancer (data based on human epidemiologic studies and animal experiences) Italy: chilli, cinnamon, clove, pepper, nutmeg => ↓ gastric cancer ánizs France and other mediterranian countries: anise, curry, ginger, mustard, paprika, pepper, allspice => ↑ bladder cancer Garam masala (mixture of pepper, clove, cinnemon, nutmeg, ginger, cardamom, caraway, laurel) => ↓ cancer incidence after DMBA treatment szegfűbors babér kömény Walnuts and oleaginous seeds (high amount of vitamin E, selenium, ellagic acid, phytic acid, phytoestrogenes => protective effect) walnut pistachio poppy-seed hazelnut sunflower seed almond pine seeds sesame seed pumpkin seed Whole Foods, Wine, and Tea Epidemiological evidence spanning many countries indicates that deaths from cancer, heart disease, and heart attacks are less common where these foods are plentiful in the diet, where tea is a beverage, or where red wine is consumed in moderation Phytochemicals Whole Foods, Wine, and Tea Historically, diets containing whole grains, fruits, vegetables, herbs, spices, teas, and red wines have been reputed to possess health-promoting qualities These foods and beverages all have something in common Phytochemicals of the flavonoid family Flavonoids Many flavonoids act as antioxidants May protect against cancers and heart disease by this mechanism More evidence is needed before any claims can be made for flavonoids themselves as the protective factor in foods Particularly when they are extracted from foods or herbs and sold as supplements Why are antoxidants important? free radicals are molecules missing electrons: unstable formation of 1 free radical causes a chain reaction with many free radicals formed antioxidants prevent formation of free radicals or break the chain reaction by becoming oxidized Antioxidants Because flavonoids often impart a bitter taste to food, food producers may refine away natural flavonoids to please consumers who generally prefer milder flavors To produce white grape juice or white wine, makers remove the red, flavonoid-rich grape skins to lighten the flavor and color of the product While greatly reducing its flavonoid content Antioxidants Whether or not research confirms the cancerfighting and heart-defending nature of flavonoids, consumers should seek out a variety of whole fruits, vegetables, and other plant-derived foods with their flavonoids intact in place of their more refined counterparts Such diets are consistently associated with low rates of disease Antioxidants Flavonoid supplements have not been proved effective or safe As for red wine, the potential health benefits may not be worth alcohol’s immediate and substantial risk Other sources: Blueberries Tea Grapes Vegetables Tea Black- most often sold, fermented and more processed Oolong- semi-fermented, heated and dried more than green tea but less than black, served in Chinese restaurants Green- unfermented, very little processing White- unfermented, very little processing, harvested before leaves are fully open Tea Calorie Free 87% of dietary flavonoids consumed Antioxident polyphenols including flavonoids Catechin EGCG Proanthocyanidins Cancer Protects against free radical damage Decrease growth of abnormal cells Associated with decreased risk of rectal, colon and skin cancer Other Benefits Memory Immune function Oral health Decreased risk of kidney stones Obesity Mostly epidemiological research and research on tea consumption, concentrated tea extracts may not be safe Antioxidants Chocolate Research subjects were instructed to eat three ounces of dark (bittersweet) chocolate chips Flavonoid antioxidants from chocolate accumulate in the blood The level of certain harmful oxidizing compounds dropped 40% The antioxidant effects of dark chocolate may turn out to be as powerful as those of tea or red wine Chocolate In theory, chocolate may also “thin the blood” by reducing the tendency of blood to clot Blood clots are a major cause of heart attacks and strokes No evidence exists to indicate that people who eat chocolate suffer fewer heart attacks or strokes than people who do not Chocolate Chocolate consumption promotes weight gain Three ounces of sweetened chocolate candy contain over 400 calories A significant portion of most people’s daily calorie allowance Chocolate contributes few nutrients save fat and sugar Antioxidants For most people, antioxidant phytochemicals are best obtained from nutrientdense low-calorie fruits and vegetables and calorie -free green or black tea With chocolate enjoyed as an occasional treat Soybeans Compared with people living in the West, Asians living in Asia suffer less frequently from: osteoporosis cancers, especially of the breast, colon, and prostate heart disease Asian women also suffer less from symptoms related to menopause Soybeans When Asians migrate to the U.S. and adopt Western diets and habits they experience these disease and problems at the same rates as native Westerners Among many differences between the diets of the two regions Asians consume far more soybeans and soy products such as miso, soy drink, and tofu than do Westerners Soybeans Soybeans contain phytochemicals known as phytoestrogens Researchers suspect that the phytoestrogens of soy foods, their protein content, or a combination of these factors may be responsible for the health effect in soy-eating peoples Research, though ongoing, is limited and inconsistent Soybeans We know with certainty that phytoestrogens are plant-derived chemical relatives of the human hormone estrogen They weakly mimic or modulate the hormone’s effects on some body tissues They act as antioxidants Soybeans We know that breast cancer, colon cancer, and prostate cancer are estrogen-sensitive They grow when exposed to estrogen It is unknown if actions of phytoestrogens may alter the course of estrogen-sensitive cancers Results from recent breast cancer studies do not support the idea unless soy is consumed beginning in childhood Soybeans: genistein Symptoms of menopause Phytoestrogens may reduce risk of adult bone loss and the sensation of elevated body temperature known as “hot flashes” A diet high in soy may offer bone protection rivaling that of hormone replacement therapy (HRT) May not reverse bone loss but may prevent it Soybeans Because HRT involves some serious health risks, supplements of soy are often sold to menopausal women as a “natural” alternative Research does not support taking phytoestrogen supplements for bone mineral retention or hot flashes Soybeans Phytoestrogen supplement use may involve some risk While studying one soy phytoestrogen, genistein, researchers found that instead of suppressing cancer growth, high doses appeared to speed division of breast cancer cells in laboratory cultures and in mice Soybeans Findings on the health effects of phytoestrogens should raise a red warning flag against taking supplements Especially in women whose close relatives have developed breast cancer Until more is known, a safer route to obtaining soy phytoestrogens is to include moderate amounts of soy-based foods in the diet As generations of Asian people have safely done through the ages Flaxseed Historically, people have used flaxseed for relieving constipation or digestive distress Currently, flaxseed and its oil are under study for potential health benefits Contains lignans, compounds converted into biologically active phytoestrogens by bacteria that normally reside in the human intestine Flaxseed Studies of populations suggest that women who excrete more phytoestrogens in the urine (an indicator of phytoestrogen intake from flaxseed and other sources) have lower rates of breast cancer Animal studies show a decrease in tumors of the breast and lung when fed flaxseed Flaxseed Studies of the direct effects of giving flaxseed to people are lacking Some risks are possible with its use Flaxseed contains compounds that may interfere with vitamin or mineral absorption Thus high daily doses could cause nutrient deficiency diseases Large quantities can cause digestive distress Flaxseed Although no clear role has been established for flaxseed in the prevention of human cancer Including a spoonful or two of flaxseed in the diet may not be a bad idea Flaxseed richly supplies linolenic acid A needed nutrient often lacking in the U.S. diet Choose most fats from sources of monounsaturated and polyunsaturated fatty acids Keep the amount within calorie needs Choose more fish, nuts and vegetable oils Use lean meats and low fat dairy products Limit saturated and trans fats To provide essential fatty acids and vitamin E while keeping calories controlled and cholesterol and saturated fat low Tomatoes People around the world who eat the most tomatoes, about 5 tomato-containing meals per week, are less likely to suffer from cancers of the esophagus, prostate, or stomach than those who avoid tomatoes Tomatoes Among the phytochemical candidates for promoting this effect is lycopene A red pigment with antioxidant activity Found in guava, papaya, pink grapefruit, tomatoes (especially cooked tomatoes and tomato products), and watermelon Tomatoes Lycopene may inhibit the reproduction of cancer cells Some research suggests that low blood levels of lycopene and related compounds correlate with increased risk of breast cancer elevated incidence of heart disease, heart attack, and stroke May also protect against the damaging sun rays that cause skin cancer Tomatoes In one study, women who consumed a diet rich in fruits and vegetables had high lycopene concentrations and a greatly reduced concentration of an indicator of cervical cancer Do scientists conclude that lycopene prevents cervical cancer? No. The suggestion is that a diet rich in fruits and vegetables with their host of nutrients and phytochemicals reduces women’s risk of cervical cancer and many other diseases Tomatoes A lesson about supplements can be learned from experience with lycopene’s chemical cousin The normally beneficial vitamin A relative betacarotene Diets high in fruits and vegetables that contain beta-carotene often correlate with low rates of lung cancer When beta-carotene supplements were given to smokers lung cancer rates increased Garlic Descriptions of its uses for headaches, heart disease, and tumors are recorded in early Egyptian medical writings In modern medical research, over 3,000 publications have investigated the potential health benefits of garlic Many have reported positive findings Garlic Among garlic’s active compounds are organosulfur compounds Reported to inhibit cancer development in laboratory animals suppress the formation of certain harmful oxidizing compounds that damage DNA and trigger cancerous changes This evidence hints that eating garlic may be beneficial against some forms of cancer in human beings Garlic More potential roles for garlic allergies heart disease bacterial cause of ulcers fungal infections reduce the clotting of the blood improve levels of blood cholesterol in people whose cholesterol is too high for heart health Garlic Volatile sulfur compounds are not present as such in intact cells. The reaction between The enzyme allinase and The volatile precursors S-alk(en)yl cysteine sulfoxide and Sulfonic acid takes place when cells are ruptured Results in the formation of Different thiosulfonates and Related sulfonic acid derivatives Garlic Studies of garlic supplements, such as powders and oils, have been disappointing Positive results seem to be associated with an aged preparation of garlic that lack garlic’s characteristic odor But is rich in antioxidants and other compounds From the scientist’s point of view, no evidence that large doses of concentrated chemicals from garlic may improve a person’s health or injure it People who eat the recommended amounts of a variety of fruits and vegetables may cut their risk of many diseases by as much as half Replacing some meat with soy foods or other legumes may lower heart disease and cancer risks In the context of a healthy diet, foods are time-tested for safety, posing virtually no risk of toxic levels of nutrients or phytochemicals What do we tell consumers? Eat more fruit Increase vegetable portions Use herbs and spices Replace some meat Add grated vegetables Try new foods MECHANISM OF ACTION ON NUTRITIONAL ANTICARCINOGENESIS I. I. Inhibition the binding to DNA brocoli, cabbage, brussels sprout, savoy cabbage (brassicans) - phenylisotiacyanats - ellagil acid greens, fruits, seeds, hazel nut - ellagil acid - flavonoids II. Inhibition of promotion green yellow vegetables, fruits (melon, squash, carrot, brussels, etc.) - retinoids - beta carotin hazel nut, seeds - vitamin E paprika, tomato, lemon, chili orange - vitamin C garlic, onion - organic sulphur chemicals curry - curcumin chili pepper - capsaicin MECHANISM OF ACTION ON NUTRITIONAL ANTICARCINOGENESIS II. III. Modulation of biotransformation brokkoli, cukkini, káposzta, kel, kínai kel, spenót, cékla, karalábé, karfiol - indol-3-carbinol garlic, grains, seal oil, olive sea-fish oils - selenium IV. Induction of physical features, changing of absorption greens, fruits, nut, hazel nut, cereals, grains - fiber greens, nut, hazel nut, cereals, fungus - riboflavin - chlorophyl Other soyabean, olive, maize, sesame, coconut oil, butter, fish coice, poultries, bran, rye Scientific publications: Questions S-ALLYLCYSTEINE INHIBITS CIRCULATORY LIPID PEROXIDATION AND PROMOTES ANTIOXIDANTS IN N-NITROSODIETHYLAMINE-INDUCED CARCINOGENESIS. ALTERED CYTOKERATIN EXPRESSION DURING CHEMOPREVENTION OF HAMSTER BUCCAL POUCH CARCINOGENESIS BY S-ALLYLCYSTEINE. DIETARY SOY AND INCREASED RISK OF BLADDER CANCER: THE SINGAPORE CHINESE HEALTH STUDY EFFECTS OF TEA ON PRENEOPLASTIC LESIONS AND CELL CYCLE REGULATORS IN RAT LIVER CHEMOPREVENTIVE EFFECT OF FARNESOL AND LANOSTEROL ON COLON CARCINOGENESIS I. FIG. 1. STRUCTURES OF FARNESOL AND LANOSTEROL FARNESOL LANOSTEROL APOPTOSIS INDUCTION BY S-ALLYLCYSTEINE, A GARLIC CONSTITUENT, DURING 7,12-DIMETHYLBENZ[A]ANTHRACENE-INDUCED HAMSTER BUCCAL POUCH CARCINOGENESIS. INDOLE-3-CARBINOL HAS POSSIBLE ANTICARCINOGENIC ACTIVITY TOMATO AND GARLIC CAN MODULATE AZOXYMETHANE-INDUCED COLON CARCINOGENESIS IN RATS IDENTIFICATION OF POTENTIAL ARYL HYDROCARBON RECEPTOR ANTAGONISTS IN GREEN TEA Phytochemicals Foodstuffs (fruits, vegetables) Ditions (isothiocyanate, benzylisothiocyanate, phenyl-ethylisothiocyanate, sulforaphan) Brassicas, peas Terpenoids (D-limonene, geraniol, menthol, carvone) Citruses Flavonoids - kvercetin - kemferol, tangeretin, nobiletin, rutin Generally all vegetables and fruits - berries, tomato, broccoli, onion - savoy cabbage, endivia, citruses, horse-radish Phenols (ellagic acid) Tea, fresh harvested fruits and vegetables, walnuts, berries Glucosinolates, indoles Brassicas Sterols (beta-sitosterol, campesterol, stigmasterol) Vegetables Coumarine compounds Manioc, citruses One of sources of the lecture: Fruits and Vegetables – The Real Thing Matters! Being Fit with Phytochemicals Mollie Smith, MS, RD California State University, Fresno Department of Food Science and Nutrition