Fruits And Vegetables A Population Studies

More than 200 epidemiological studies have investigated the relationship between vegetable and fruit consumption and the risk of cancer. When examining the studies of all cancer sites, more than three quarters of these studies show a significant reduction in risk for a higher intake of at least one vegetable or fruit category.3 People who eat higher amounts of fruits and vegetables have about one half the risk of cancer and less mortality from cancer.4,5 Pickled vegetables would not be included in the list of recommended vegetables, since these have been associated with an increased risk of esophageal cancer.6 Fruits and vegetables are most effective against those cancers that involve epithelial cells, such as cancer of the lung, cervix, esophagus, stomach, colon, and pancreas. Results from a large-scale Italian study revealed that relative risk of common epithelial cancers ranged from 0.2 to 0.5, for the highest tertile, compared with the lowest tertile of vegetable intake.7 High intakes of fruit provided reduced risk of many epithelial cancers although the protection was generally less than that seen with a high vegetable intake.

The protective effect of vegetables has also been observed for hormone-related cancers, such as breast cancer. A recently published case control study found a strong inverse association between total vegetable intake and breast cancer risk in premenopausal women.8 A risk reduction of 54% was seen in women with the highest intake of vegetables compared with those with the lowest intake. The protective effect appeared to be due to the synergistic effect of a variety of substances in the vegetables. A Greek study also noted that vegetable and fruit consumption was independently associated with significant reductions in the incidence of breast cancer.9 Women consuming four to five servings of vegetables per day had a 46% lower risk of breast cancer, compared with women consuming less than two servings a day. Furthermore, women consuming six servings of fruit a day had a 35% lower risk of breast cancer than women consuming less than two servings a day.

Different fruits and vegetables have been investigated separately and appear to provide protection against cancer at certain locations. For example, the use of carrots and green, leafy vegetables provides substantial protection against lung and stomach cancers, while the cruciferous vegetables (cabbage, broccoli, cauliflower, etc.) provide useful protection against colorectal and thyroid cancers. In addition, the regular use of onions or garlic can decrease the risk of stomach and colon cancer by 50-60%,3,10,11 while the regular consumption of tomatoes and strawberries was recently found to substantially protect against prostate cancer.12

A regular fruit and vegetable consumption may also reduce the risk of ischemic heart disease.13,14 A study of 11,000 health conscious people in the U.K. noted that a daily consumption of fresh fruit was associated with a 24% reduction in mortality from heart disease and a 32% reduction in death from cerebrovascular disease, compared with less frequent fruit consumption. Daily consumption of raw salad was associated with a 26% reduction in mortality from heart disease.15

Stroke kills over 150,000 Americans a year. Research at Harvard found that persons in the highest quintile of fruit and vegetable intake (men who consumed an average of 5.1 servings/day and women who consumed an average of 5.8 servings/day) experienced a 31% lower risk of stroke, than those in the lowest quintile (men and women consuming less than three servings a day). Cruciferous vegetables, green leafy vegetables, citrus fruits and citrus juices, but not potatoes or legumes, contributed the most to the protective effect of fruit and vegetables.16

The World Health Organization has recommended that, for good health, we consume at least 400 grams (14 ozs.) of fruits and vegetables a day.17

The National 5-A-Day for Better Health campaign was designed to increase the consumption of vegetables and fruit to at least five servings a day. When surveyed, only one in 11 Americans actually met this recommended guideline.18 A lack of knowledge about the value of fruit and vegetables possibly explains the low intake. Two out of every three Americans surveyed said they thought that not more than two servings of fruit and vegetables a day were sufficient for good health.19

A high intake of fruit and vegetables is often associated with a lower meat intake and hence, a reduced saturated fat intake. Fruit and vegetables are known to be rich in dietary fiber, folic acid, potassium, magnesium, vitamin C, and other micronutrients that provide protection against cardiovascular disease and cancer. Beyond all these factors, there are additional protective substances: the phytochemicals.

B. Phytochemical Feast

A variety of foods have been reported to be cardio-protective and cancer-preventive. The foods and herbal seasonings that have been reported to exhibit anticancer activity include soybeans, the cruciferous vegetables, the umbelliferous vegetables (carrots, celery, cilantro, caraway, dill, fennel, parsley, and parsnips), flax, citrus, garlic, onions, ginger, turmeric, licorice root, solanaceous vegetables (tomatoes and peppers), brown rice, whole wheat, oats, cucumber, cantaloupe, berries, green tea, and the Labiatae herbs (mints, rosemary, thyme, oregano, sage, basil).20

A host of cancer-preventive and cardio-protective phytochemicals have been identified in these foods (see Table 14.1).21 Some of these phy-tochemicals may reduce the risk of cardiovascular disease by improving blood flow, inhibiting LDL oxidation, inhibiting platelet aggregation, interfering with cholesterol absorption and modulating cholesterol metabolism. The phytochemicals effectively involved in these processes include the carotenoids, flavonoids, tocotrienols, terpenoids, isoflavones, phytosterols, and various sulfur compounds from the Allium herbs. Furthermore, many of these phytochemicals block various hormone actions and metabolic pathways that are associated with the development of cancer; stimulate the immune system; block the formation of adducts between DNA and a carcinogen; induce phase I enzymes (such as cytochrome P-450) and phase II enzymes (such as glutathione-S-transferase); and have antioxidant activity.1,11,20,22-28

For example, the indoles in cruciferous vegetables strongly induce estrogen 2-hydroxylase, which produces metabolites that decrease the risk of cancer.22 Sulforaphane, the isothiocyanate in cruciferous vegetables,

Table 14.1 Health-Promoting Phytochemicals in Plants21

Phytochemical

Food Source

Carotenoids

Yellow-orange vegetables and fruits; green,

leafy vegetables; red fruits

Coumarins

Celery, parsnips, figs, parsley

Curcumins

Turmeric, ginger

Dithiolthiones

Cruciferous vegetables

Ellagic acid

Grapes, strawberries, raspberries, nuts

Flavonoids

Most fruits and vegetables

Indoles, isothiocyanates

Broccoli, cabbage, cauliflower, Brussels

sprouts, and radish

Isoflavones

Soybeans, tofu

Glucarates

Citrus, grains, tomatoes, bell peppers

Lignans

Soybeans, flax seed

Liminoids

Citrus

Phthalides, polyacetylenes

Caraway, celery, cumin, dill, fennel, parsley,

carrots, coriander

Phenolic acids

Berries, grapes, nuts, whole grains

Phytates

Grains, legumes

Phytosterols

Seeds, legumes

Protease inhibitors

Grains, seeds, nuts, legumes

Saponins

Legumes, herbs

Sulfides

Onions, garlic, chives, leeks

Terpenes

Cherries, citrus, herbs

Tocotrienols

Nuts, seeds

and especially broccoli, induces phase II enzymes that detoxify carcinogens. Broccoli sprouts are reported to have 10-100 times the cancer-protective activity of mature broccoli plants.29 The activity in the sprouts is largely due to glucoraphanin, a precursor of sulforaphane. The citrus flavonoids, tangeretin and nobiletin, are known to activate the detoxifying P-450 enzyme system and are potent inhibitors of tumor cell growth.30 Limonin and nomilin, the principal limonoids in citrus, occur in high concentrations in grapefruit and orange juice, and partly provide the bitter taste in citrus. These limonoids possess the ability to inhibit tumor formation by stimulating the enzyme glutathione S-transferase.31 The pulp and albedo of an orange and other citrus are rich in glucarates, which significantly reduce the incidence and multiplicity of mammary tumors, and increase tumor latency.32 The oil in orange rind contains substantial amounts of limonene, a terpenoid that possesses anti-cancer activity.33

C. Carotenoids

Hundreds of carotenoids have been identified in plants. These pigments are responsible for the yellow-orange and red colors of many of the commonly eaten fruits (such as mango, citrus, peach, pineapple, tomato, strawberries, apricots, guava, watermelon, cantaloupe) and vegetables (such as carrots, pumpkin, sweet potato).34 Dark-green leafy vegetables are also rich sources of carotenoids. In all cases, the deeper the color, the greater the amount of carotenoid pigment. Persons with a high carotenoid intake or who have high levels of serum carotenoids have a reduced risk of cancer.35,36 The carotenoids have significant antioxidant activity and the ability to quench free radicals, thereby protecting DNA, cell membranes, and other cellular components from oxidative damage that might lead to the development of tumor cells. The consumption of tomato products substantially reduces the susceptibility of DNA to oxida-tive damage.37

High levels of lycopene are found in the prostate. The consumption of tomato products, rich in the red lycopene pigment, is associated with a reduced risk of prostate cancer. In the Adventist Health Study, men who consumed tomatoes more than five times a week had a 40% lower risk of prostate cancer than men consuming tomatoes less than once a week.38 In the Health Professionals Study, lycopene intake was inversely related to risk of prostate cancer.12 Risk of prostate cancer was 22% lower and 35% lower in those men consuming four to seven servings per week and more than 10 servings of tomato products per week, respectively, compared with those consuming less than 1.5 servings per week. Studies also suggest that lycopene may play a role in protection against cancer of the breast and cervix.39,40 Tomato and tomato-based products account for over 85% of dietary lycopene in American diets. The rich sources of lycopene (given in pg lycopene per g wet weight) include fresh tomatoes (9-42), tomato paste (54-1500), tomato juice (50-116), pizza sauce (127), watermelon (23-72), pink guava (54), pink grapefruit (34) and papaya (20-53).41 Many factors influence the absorption and bioavailability of lycopene, such as heat and food processing and the presence of dietary fat. The availability of lycopene from tomato paste was found to be greater than from fresh tomatoes. Lycopene concentrates in LDL and VLDL serum fractions.41

Carotenoids protect against cholesterol oxidation. Persons with high levels of serum carotenoids have a reduced risk of heart disease.25,42 The recent EURAMIC study found that a high intake of lycopene (the red pigment in tomatoes, pink grapefruit, guava, and watermelon) in men was associated with a 48% lower risk of a myocardial infarction, compared with a low intake of lycopene.43 Carotenoids act as modest hypocholes-terolemic agents, secondary to their inhibitory effect on HMG-CoA

reductase, the rate-limiting enzyme in cholesterol synthesis. Cholesterol synthesis is suppressed and LDL receptor activity is augmented by the carotenoids te-carotene and lycopene, similar to that seen with the drug fluvastatin. When lycopene supplements (60 mg/day) were given to men for a 3-month period, a 14% reduction in their LDL cholesterol levels occurred.44 Therefore, lycopene may be useful for decreasing the risk of coronary heart disease.

Citrus fruits contain a variety of carotenoids. Pink grapefruits have a high content of lycopene and te-carotene, while other citrus (such as tangerines, oranges) contain high levels of different carotenoids (lutein, zeaxanthin, te-cryptoxanthin)34 that have significant antioxidant activity. These carotenoids are associated with a lower incidence of age-related macular degeneration,45 the leading cause of vision loss in Americans after the age of 55. A diet rich in carotenoids (such as lutein, zeaxanthin or te-carotene) enhances several aspects of immune function in the body, including those linked to tumor cell destruction.46

Carotenoids, along with other antioxidants, may play a role in preventing age-related cataracts. In the Nurses' Health Study, an increased intake of spinach and kale (foods rich in the carotenoid lutein) was associated with a moderate decrease (22%) in risk of cataract.47 In the Health Professionals' Study, broccoli and spinach consumption were consistently associated with a lower risk of cataract. Men in the highest quintile of lutein and zeaxanthin intake (carotenoids found in green vegetables) had a 19% lower risk of cataract, relative to men in the lowest quintile.48

D. Flavonoids

Polyphenols constitute one of the most numerous groups of plant metabolites. They include molecules such as coumarins, the 13 classes of flavonoids (numbering over 5000 substances), as well as highly polymerized compounds such as lignans and tannins. In berries, the main polyphenols are anthocyanins; fruits and vegetables are rich in phenolic acids, citrus are rich in flavonoids, and vegetables are rich in flavonoids and coumarins.49

The many flavonoids in fruit and vegetables have extensive biological properties that reduce the risk of cardiovascular disease. Flavonoids are among the most potent antioxidants. They protect LDL cholesterol from oxidation; inhibit the formation of blood clots; and have vasopressive and hypolipidemic effects and anti-inflammatory action.49,50 Some polyphenols have hypocholesterolemic effects mediated by reduced intestinal cholesterol absorption and increased bile acid excretion. European studies have found flavonoid intake to be inversely associated with heart disease mortality, and the incidence of heart attack and stroke over a 5-year period.51-53 Those who had the highest consumption of flavonoids had 60% less mortality from heart disease and 70% lower risk of stroke than the low-flavonoid consumers. Among other things, flavonoids extend the activity of vitamin C, and have anti-tumor activity.50 The citrus flavonoids, tangeretin and nobiletin, are known to be potent inhibitors of tumor cell growth and can activate the P-450 enzyme system.30

The flavonoid content of a food depends on the growing conditions, the part of the plant consumed, the degree of ripeness, and method of processing. The levels are greater in immature organs of the plant where there is active cell division, and in external tissues exposed to sunlight. Fruits have a relatively high level of flavonoids, especially when ripe. Peeling will eliminate a substantial amount of flavonoids, since the skin contains 8- to 10-fold more than the pulp. Flavonoid levels in processed foods (canned, in glass jars, or frozen) are significantly lower than in fresh products. Flavonoids are carried in the LDL particle along with other antioxidants such as vitamin E and carotenoids. The oxidation of LDL cholesterol can occur only when these endogenous antioxidants are exhausted.50

E. Pigments in Grapes and Cherries

Anthocyanin pigments, the water-soluble, reddish pigments found in fruits such as strawberries, cherries, cranberries, raspberries, blueberries, grapes, and black currants, are reported to be antioxidants and are very effective in scavenging free radicals, inhibiting LDL cholesterol oxidation and platelet aggregation, and protecting against cardiovascular disease.54-56 A variety of anthocyanins and flavonoids have been identified in tart cherries, which possess very strong antioxidant and anti-inflammatory activity. These compounds could account for antiallergenic, antiviral, anticancer, and cardio-protective activities.57 It has been suggested that the composition of tart cherries may protect against various chronic diseases and reduce arthritic- and gout-related pain.57

The regular use of red wine is suggested for lowering the risk of heart disease. Two possible mechanisms explain this effect. First, alcohol raises HDL cholesterol levels.58 Second, wine inhibits the formation of blood clots. Since purple grape juice and dealcoholized red wine inhibit platelet aggregation, it is clearly not an effect of alcohol, but appears to be related to the flavonoid pigments in the grape juice or wine.59,60 Dealcoholized red wines and red grape juice inhibit platelet aggregation by blocking thromboxane B2 synthesis in the platelets. This inhibition was found to be in direct proportion to the content of a stillbene, trans-resveratrol, which is found in wine and grape juice.59 Resveratrol is a phytochemical found mainly in the skins of grapes and is readily transferred to red wine by alcohol extraction. It is also recovered during the hot-press-extraction process in the manufacture of purple grape juice.

Dealcoholized red wine and red grapes are also rich in phenolic compounds such as anthocyanins, flavonols, flavan-3-ols, and hydroxy-cinnamates, which act as antioxidants. These compounds strongly inhibit LDL oxidation and diminish the development of atherosclerotic plaque formation.61-64 The antioxidants in wine and grape juice may be even more potent than vitamins C and E.63,64 In a new study from the University of Wisconsin, grape juice was shown to improve blood flow by 6.4% and protect LDL from oxidation by 35.4%. Wines also contain lignans, with the red wines having four to nine times more lignans than the white wines.65 White wine, white grape juice, and green grapes generally have polyphenolic compounds similar to the red varieties, but occur in lesser amounts.55

In preliminary studies, the stilbene, resveratrol, has been shown to reduce the risk of breast, colon, and liver cancers. Dannenberg has shown that resveratrol inhibits cyclooxygenase-2, an enzyme linked to breast cancer.66 Others have shown that compounds in grapes inhibit breast cancer by suppressing the estrogen-producing enzyme aromatase.67

F. Isoprenoids and Phenolics

Fruits, vegetables, and cereal grains contain a variety of isoprenoid compounds that exhibit anticancer activities. These compounds, which derive from mevalonate metabolism, include the tocotrienols and monoterpenes such as limonene, geraniol, menthol, carvone, and perillyl alcohol. The isoprenoids can suppress tumor growth by inhibiting HMG-CoA reductase, the rate-limiting step in cholesterol synthesis. Overall, the terpenoids and tocotrienols increase tumor latency and decrease tumor multiplicity.68 In addition, many of the terpenoids such as limonene, geraniol, menthol, and carvone exhibit anti-tumor activity by stimulating the activity of the phase II enzyme, glutathione S-transferase. Finally, the terpenoids may also facilitate a reduction in blood cholesterol levels.69,70

A whole variety of phenolic compounds are widely distributed in fruits and vegetables. These phenolics act as antioxidants and influence the sensory quality and stability of foods. Many of these compounds (such as caffeic, ellagic and ferulic acids, sesamol and vanillin) exhibit anticar-cinogenic activity and inhibit atherosclerosis.24 Ellagic acid, in raspberries and strawberries, inhibits certain carcinogen-induced cancers and has other chemopreventive properties. Ellagic acid also has a role in cell cycle regulation of cancer cells.71 A number of fruits and vegetables contain the phytoestrogenic lignans. Those with the highest level of lignans were found to be strawberries, pomegranates, cranberries, melons, asparagus, pumpkin, chives, guava, broccoli, black currant, and garlic.65 The predominant lignan measured in these foods was secoisolariciresinol, with much lesser amounts of matairesinol.

G. Fructose Oligosaccharides

Fructose oligosaccharides (FOS) are widely distributed in plants, with the best sources being artichokes, onions, garlic, leeks, wheat, dandelion greens, asparagus, banana, and rye.72 About 95% of FOS, or oligofructose, in the American diet comes from wheat and onions, with another 4% being derived from bananas and garlic.72 The functional and nutritional properties of oligofructose have led many to see its significance and value in the human diet. Oligofructose can be considered a carbohydrate, similar to dietary fiber. It has been used to replace sugar in foods due to its sweet, pleasant flavor and high solubility. It causes a shift in the composition of colonic microflora by selectively stimulating the growth of bifi-dobacteria.73 Other health-promoting properties reported for oligofructose include increasing intestinal motility, decreasing blood triglycerides and blood cholesterol levels, blunting of alimentary glycemia, decreasing the growth rate of tumors, increasing the absorption of calcium and magnesium, and enhancing the immune system.73

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