Articles > Phytochemicals: Guardians of Our Health

Phytochemicals: Guardians of Our Health
A Continuing Education Article

Increasingly, Americans are being told to eat more plant foods (1). The optimal diet that is recommended by most professional health organizations is a low-fat, low-saturated fat, high-complex carbohydrate diet characterized by a frequent consumption of vegetables, fruit, whole-grain bread, rice and pasta. The WHO study group on diet, nutrition and prevention of communicable diseases recommended that we daily consume at least 400 grams (14 ozs) of fruits and vegetables, including at least 30 gm (1 oz) of pulses, nuts and seeds (2).

Consuming a diet rich in such plant foods will provide a milieu of phytochemicals, non-nutritive substances in plants that possess health-protective effects. Nuts, whole grains, fruits and vegetables contain an abundance of phenolic compounds, terpenoids, pigments and other natural antioxidants (including vitamins A, C and E) that have been associated with protection from and/or treatment of chronic diseases such as heart disease, cancer, diabetes, and hypertension as well as other medical conditions (3). In addition to the phytochemicals, fruits and vegetables are naturally low in fat, saturated fat, cholesterol, calories and sodium, and are rich in potassium, fiber, folic acid and vitamin C.

Eat more fruits and vegetables

n eighty-two percent of 156 dietary studies reviewed recently, it was found that fruit and vegetable consumption provided significant protection against many cancers (4). People who eat higher amounts of fruits and vegetables have about one-half the risk of cancer and less mortality from cancer (5,6). 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). The protective effect of vegetables was also observed for hormone-related cancers. Higher intakes of fruit provided reduced risk of many epithelial cancers although the protection was generally of a lesser magnitude.

At present there is a nationwide campaign to promote an increased use of fruits and vegetables. The "5-a-Day for Better Health" program was designed to encourage the consumption of at least five servings a day of fruit and vegetables. The average American eats only about one and one-half servings of vegetables per day and less than one serving of fruit per day. A recent survey of American eating habits showed that only 1 in 11 Americans met the guidelines for eating at least 3 servings a day of vegetables and at least 2 servings a day of fruit (8). In fact, one in every nine Americans surveyed ate no fruit and no vegetable on the day of the survey, and 45% reported eating no fruit that day. When asked how many servings of fruits and vegetables someone should eat every day for good health, people gave amazing answers. Two out of every three Americans surveyed said they thought that only 2 or fewer servings were sufficient for good health (9).

A recently published study of 2400 Greek women noted that vegetable and fruit consumption were independently associated with significant reductions in the incidence of breast cancer (10). Women with the highest intake of vegetables (4-5 servings/day) had a 46 percent lower risk of breast cancer compared with women that had the lowest vegetable intake (less than 2 servings/day). Women with the highest intake of fruit (6 servings/day) had a 35 percent lower risk of breast cancer compared with women that had the lowest fruit intake (less than 2 servings/day).

Plant protection

The National Cancer Institute has spent in excess of $20 million over the past 5 years researching the anticancer potential of plant foods (11). The foods and herbs with the highest anticancer activity include garlic, soybeans, cabbage, ginger, licorice, and the umbelliferous vegetables (including carrots, celery, cilantro, parsley, and parsnips). Foods with a modest level of cancer-protective activity include onions, flax, citrus, turmeric, cruciferous vegetables (broccoli, Brussels sprouts, cabbage and cauliflower), solanaceous vegetables (tomatoes and peppers), brown rice and whole wheat. Other foods and herbs that were found to contain a measure of anti-cancer activity included oats and barley, mints, rosemary, thyme, oregano, sage, basil, cucumber, cantaloupe and berries (11).

Research has identified a host of active substances in these foods that provide the protection against cancer. These phytochemicals include allyl sulfides in garlic and onions; phytates in grains and legumes; glucarates in citrus, grains and solanaceous vegetables; lignans in flax and soy beans; isoflavones in soy beans; saponins in legumes; indoles, isothiocyanates and dithiolthione in cruciferous vegetables; ellagic acid in grapes, strawberries, raspberries and nuts; phthalides and polyacetylenes in the umbelliferous vegetables; and a whole range of flavonoids, carotenoids and terpenoids in various plant foods. These beneficial chemicals block various hormone actions and metabolic pathways that are associated with the development of cancer (11,12).

Estrogens can be metabolized by cytochrome P-450 enzymes to produce 2-hydroxyestrogens or 16 alpha-hydroxyestrogens. The relative activity of these two pathways in an individual determines risk for hormone-dependant cancers. Hydroxylation at C-16 leads to metabolites that promotes estrogen action and increases risk of breast and uterine cancer while C-2 hydroxylation produces metabolites that oppose estrogen action and decreases cancer risk (13). Lifestyle factors influence the activity of these two pathways. For example, obesity suppresses C-2 hydroxylation while aerobic exercise elevates it. The C- 16 pathway is elevated by high-fat diets. Phytochemicals in our food can alter the relative activities of these pathways. Indole-3-carbinol in cruciferous vegetables is a powerful inducer of the enzyme estrogen 2-hydroxylase (13).

Are the phytochemicals destroyed by cooking? Most of the compounds are heat stable and are not significantly lost in the cooking water. While vitamin C is partially lost by cooking, the availability of carotenoids and the level of indoles in broccoli may actually be increased during cooking(14).

Less cancer with soy

Soybeans contain fairly high levels of several compounds with demonstrated anti-cancer activity, including phytates, protease inhibitors, phytosterols, saponins and isoflavonoids (15). Consumption of soybeans is suggested as a contributing factor in the low incidence of breast and prostate cancer in Japanese women and men, respectively. Chinese having a regular consumption of soybeans and/or tofu have only one-half as much cancer of the stomach, colon, rectum, breast, and lung compared with those Chinese who rarely consume soy or soy products (16)

Soybeans, and non-fermented soy products such as tofu, are a very rich and unique source of the isoflavones, genistein and diadzein. These isoflavonoids inhibit the growth of hormone-dependant and hormone-independent cancer cells in culture (17). The isoflavones in soy have been shown to inhibit the growth of both human breast cancer and prostate cancer (16). A low mortality from prostatic cancer is seen in Japanese men who consume a low-fat diet high in soy products. Decreased prostatic cancer is also seen in Hawaiian men of Japanese descent who regularly eat rice and tofu.

Estrogens can stimulate the growth of mammary tumors in experimental animals. Genistein in soy acts as a weak antiestrogen, competitively binding to the estrogen receptors and reducing the synthesis and activity of endogenous estrogen (18). Hence, genestein can function as an estrogen antagonist and reduce the risk of promoting the growth of estrogen-sensitive tumors. One can obtain substantial levels of dietary isoflavones by a daily consumption of an ounce or two of soy protein. One- half cup of soybeans, one cup of soy beverage, or 4 ounces of tofu can provide about 30-40 mg of genestein (19).

Soy also lowers cholesterol

A number of human studies over the past 20 years have shown that persons who daily consume about 1 to 2 ozs of soy protein for about 4 weeks can experience a decrease in their total and LDL cholesterol levels of as much as 10 to 20 percent when initial blood cholesterol levels are elevated (20). In some instances, persons with normal blood cholesterol levels may also enjoy the benefit of lowered blood lipid levels by consuming soy. While LDL levels are decreased, HDL cholesterol levels normally remain unchanged.

The use of soy also lowers triglyceride levels, especially in subjects with elevated blood triglyceride levels. The blood lipid responses tend to be more pronounced in younger adults than in older adults. The reductions are normally greater in subjects with high initial cholesterol levels. A recent meta-analysis of 38 controlled, clinical trials found that an average intake of 47 gms of soy protein per day produced on average a 13 percent decrease in LDL cholesterol levels and a 10 percent decrease in triglyceride levels (21).

As little as 1 to 2 ozs of isolated soy protein incorporated into muffins, breads, cookies, and other commonly eaten bakery items can effectively lower the cholesterol levels of men who initially had cholesterol levels above 220 mg/dl (22). Simply replacing milk with a soy beverage has been shown to cause blood cholesterol levels to decrease about 5 to 10% and LDL cholesterol levels to drop 10 to 20 percent within 4 weeks (23). It is obvious that very modest changes in our diet appear to have a measurable effect on blood lipid levels.

The mechanism for the action of soy is not known with certainty at this time. The soy isoflavones are potent inhibitors of cholesterol synthesis, and the plant sterols (for example, beta-sitosterol) and saponins in soy can block cholesterol absorption from the diet or increase cholesterol excretion from the body (24).

Phytochemicals in citrus

Citrus, in addition to its ample supply of vitamin C, folic acid, potassium and pectin, contains a host of active phytochemicals that also protect our health. In fact, there are over 170 phytochemicals in an orange (25). The more than 60 flavonoids in citrus possess a wide range of properties including anti- inflammatory and antitumor activity, inhibition of blood clots and strong antioxidant activity (26). The flavonoids, tangeretin and nobiletin, are known to be potent inhibitors of tumor cell growth and can activate the detoxifying P-450 enzyme system (27).

There are about 40 limonoids in citrus, with limonin and nomilin being the principal ones. These compounds, which occur in high concentrations in grapefruit and orange juice, partly provide the bitter taste in citrus. Limonoids possess the ability to inhibit tumor formation by stimulating the enzyme glutathione S-transferase (GST) (28). GST is a detoxifying enzyme that catalyzes the reaction of glutathione with dangerous electrophiles to form less toxic and more water-soluble compounds that can be easily excreted from the body.

Orange and lemon oil contain substantial amounts of limonene, a terpenoid that also possesses anti-cancer activity (29). Citrus pulp and the albedo (the white of the orange) is rich in glucarates. These substances are being studied for their potential to prevent breast cancer and to lower the risk of symptoms of premenstrual syndrome (25).

There are about 20 carotenoids in an orange. Pink grapefruit have a high content of beta- carotene, while other citrus (such as tangerines, oranges) contain high levels of other carotenoids (lutein, zeaxanthin, beta-cryptoxanthin) (30) that have significant antioxidant activity. These carotenoids are associated with a lower incidence of age-related macular degeneration, the leading cause of blindness in the US after age 65 (31). Pink grapefruit also contains a high level of 1ycopene, the red pigment in tomatoes and guava that has a significant anti-tumor activity.

Protection from whole grains

The phytochemicals found in fruit and vegetables are very similar to those located in whole grains. The phytochemicals that are found in grains include plant sterols, phytases, phytoestrogens, tocotrienols, lignans, ellagic acid, and saponins (32). These substances reduce the risk of cardiovascular disease and cancer. The active phytochemicals are concentrated in the bran and the germ, so that the health benefits of grains are maximized when the whole grain product is consumed. Refining wheat, for example, causes about a 200 to 300-fold loss in the phytochemical content (33).

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 (related to the tocopherols), and monoterpenes such as limonene, geraniol, menthol, carvone, beta-ionone, perillyl alcohol (34). Since tumor cells synthesize and accumulate cholesterol faster than normal cells, the isoprenoids can suppress tumor growth by inhibiting HMG-CoA reductase (the rate limiting step in cholesterol synthesis).

In addition, terpenoids such as limonene, geraniol, menthol and carvone act as anticarcinogens by inducing the detoxifying enzyme GST (34). Overall, the terpenoids and tocotrienols increase tumor latency and decrease tumor multiplicity. In addition, these same compounds elicit a significant reduction in total and LDL cholesterol levels (34-36), thereby reducing the risk of heart disease.

Benefits of flax

Flour derived from flax seed is increasingly being used in bread and bakery products to provide not only a nutty flavor but also to increase the nutritional and health benefits of the final product. The use of flax seed can lower both blood cholesterol and LDL cholesterol levels due to its very low saturated fat content (37). Flax seed oil is one of the richest known sources of omega-3 fat, since linolenic acid comprises 55 percent of the oil. This provides flax with its anti-inflammatory effect (and hence the possible usefulness for the treatment of lupus, arthritis, and different allergies) and the ability to boost the immune system (38).

Flax seed is also an extremely rich source of lignans. Plant lignans are converted to mammalian lignans (enterolactone and enterodiol) by bacterial fermentation in the colon (39). These mammalian lignans appear to be anticarcinogenic. The lignan metabolites bear a structural similarity to estrogens and can bind to estrogen receptors and inhibit the growth of estrogen-stimulated breast cancer (40-42). Urinary excretion of lignans is reduced in women with breast cancer, while the consumption of flaxseed powder increases the urinary level of lignans by 8 to 18-fold (43).

Flavonoids

The many flavonoids in plants (fruit, vegetables, nuts and grains) have extensive biological properties that promote human health and help reduce the risk of disease. Flavonoids extend the activity of vitamin C; act as antioxidants; protect LDL cholesterol from oxidation to the unsafe cholesterol oxides; inhibit platelet aggregation; and have anti-inflammatory and anti-tumor action (44,45).

Quercetin is the major flavonol in the Western diet. Rich sources of quercetin are red and yellow onions, kale, broccoli, red grapes, cherries, French beans, apples and cereals. Quercetin possesses both anticarcinogenic activity and the ability to inhibit LDL oxidation (46). The Zutphen study of elderly men in the Netherlands found that the flavonoid intake was inversely associated with heart disease mortality and incidence of heart attack over a five-year period. Those who had the highest consumption of flavonoids had 60% less mortality from heart disease than the low flavonoid consumers (47).

Red wine and grape juice (but not white wine) contain a significant level of phenolic flavonoids and red anthocyanin pigments. These compounds can act as antioxidants, protect against LDL oxidation and inhibit platelet aggregation, thereby providing protection against heart disease (48-50). The phenolic components of red wine, rather than the alcohol content, have been shown to reduce the levels of LDL cholesterol and lipoprotein (a) (51). Substantial levels of the phenolic antioxidant compounds are found in grapes and unfermented grape juice (44).

A whole variety of phenolic compounds, in addition to the flavonoids, are widely distributed in grains, fruits, vegetables and herbs so that it is not uncommon for one to consume up to 1 g of phenolic compounds per day. These phenolics influence the quality, acceptability and stability of foods by acting as flavorants, colorants and antioxidants (52). The phenolic compounds (such as caffeic, ellagic and ferulic acids, sesamol and vanillin) also exhibit anticarcinogenic activity and inhibit atherosclerosis (52).

Color your life

Pigments provide a lot of color to our food and enhance the enjoyment of the eating experience. Presently, there are almost 2000 known plant pigments in our food, including over 800 flavonoids, 450 carotenoids and 150 anthocyanins (53). These pigments do more than just appeal to our senses; they also protect us from disease.

Anthocyanins are the water soluble, reddish pigments found in many fruits, such as strawberries, cherries, cranberries, raspberries, blueberries, grapes and black currants. Since anthocyanins inhibit HMG-CoA reductase and thereby inhibit cholesterol synthesis these fruits provide protection against heart disease. The carotenoids are powerful antioxidants that act to quench free radicals and provide protection against oxidative damage, and stimulate immune function. Persons with high levels of serum carotenoids have a reduced risk of heart disease and cancer (54-56). Carotenoids are the pigments found in yellow-orange, red and green vegetables and the yellow-orange fruits.

Several large-scale, randomized trials (such as the Physicians' Health Study and the Women's Health Study) are in progress to determine the health benefits and safety of well-nourished populations taking beta-carotene and other antioxidant supplements. Results from some of the clinical trials have been disappointing to some in that the supplements were unable to provide any substantial protective effect against heart disease or cancer (57). On the other hand, the consumption of foods naturally rich in beta- carotene, lycopene, lutein or other carotenoids is consistently associated with a lower risk of cancer or heart disease (54,55).

The pigments isolated from the bean seed coat of Phaseolus vulgarus, the common bean, exhibit strong antioxidative activity. These anthocyanin pigments play an important role in chemically protecting the bean from oxidative damage (58). When the beans are ingested the pigments may also provide protection to the consumer against oxidative damage of cell membrane lipids, and supplement the work of vitamins C and E.

Additional protection from herbs

Compounds that stimulate the activity of glutathione S-transferase (GST) are considered as inhibitors of cancer. Substances that stimulate GST activity include the phthalides in celery seed, the sulfides in garlic and onions, the dithiolthiones and isothiocyanates in broccoli and other cruciferous vegetables, the bitter liminoids in citrus and the curcumins in ginger and turmeric (12,28,59).

Rosemary, sage, oregano, thyme and other flavoring herbs that belong to the Labiatae family are known to possess strong antioxidative activity (60). For example, rosemary and sage contain substantial levels of carnosol and ursolic acid, potent antioxidants that possess anti-tumor activity (61). Ginger contains a dozen phenolic compounds, known as gingerols and diarylhaptanoids, that have an antioxidant activity that is even greater than alpha-tocopherol (vitamin E) (62). The compounds responsible for the flavors of many common herbs and seasonings are terpenoids, similar to those mentioned earlier in fruits, vegetables and cereal grains. The terpenoids in herbs are reported to be useful cancer chemopreventive agents (63-67).

Garlic, onions and other members of the Allium family are rich in sulfides and other protective substances. Garlic contains a number of allyl sulfides that are known to decrease the tendency of blood clots to form, significantly lower total and LDL cholesterol levels and decrease the risk of cancer at many sites (68,69). Clearly, a diet in which herbs are generously used to flavor the food will provide a variety of active phytochemicals that promote health and protect against chronic diseases. A number of other frequently used herbal products are reported to provide protection or relief from a variety of common ailments (70).

Conclusion

Clearly, with such a wide variety of protective phytochemicals in fruits, vegetables, whole grains, nuts, legumes and herbal seasonings the regular consumption of these foods is essential to ensuring a healthier population that has lower rates of heart disease and cancer (3). According to the USDA Food Guide Pyramid it is recommended that adults consume between 5 and 9 servings a day of fruits and vegetables. Since very few Americans achieve that level of consumption many could surely benefit from a substantial increase in their use of fruits and vegetables.

While the antioxidant vitamins C and E and beta-carotene apparently have a low toxicity (71), the benefits of a regular and long-term intake of antioxidant supplements are far from conclusive and await further verification from the large-scale intervention trials (57,72). On the other hand, the regular consumption of foods that are naturally high in antioxidants (fruits, vegetables and whole grains) is positively associated with substantial health benefits. These foods contain hundreds of antioxidants, and at least some of them act synergistically (73). Furthermore, the safety of consuming concentrated extracts of fruits and vegetables that contain very high levels of phytochemicals is unknown and unwarranted at this time. The protective benefits of a phytochemical-rich diet is best obtained from a frequent consumption of fruits, vegetables and whole grain products.

 

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