MORE AND MORE consumers are discovering that phytochemicals are good for their health. What are they? What do they do? Phytochemicals are naturally occurring substances in plants that provide color, texture, and flavor for plant foods. They also provide a defense system for the plant, against microorganisms and insects. These phytochemicals also protect us in different ways.

A host of different phytochemicals have been identified in fruits, vegetables, whole grains, nuts, seeds, legumes, and herbs (see Table 1). These phytochemicals possess health-promoting properties useful for the treatment and prevention of chronic diseases, such as cancer and cardiovascular diseases.

Fruits and Vegetables Protect

Many studies have shown that a high intake of fruit and vegetables is associated with a substantial reduction in the risk of various cancers, coronary heart disease, and stroke. In a recent Harvard study the adjusted risk of stroke was reduced 31 percent for those with the highest intake of fruit and vegetables versus the lowest intake.

A recently conducted study from Finland found that a high intake of fruit, vegetables and berries was associated with a 35 percent lower risk of all-cause mortality. Why? They contain little fat and salt, are rich sources of folic acid, potassium and fiber, and are known to be excellent sources of health-promoting phytochemicals.

Persons with a high dietary intake and high serum levels of carotenoids have a substantially reduced risk of cancer. The carotenoids have significant antioxidant activity and the associated ability to quench free radicals, thereby protecting the cell from oxidative damage that may lead to the development of tumor cells.

In addition, a diet rich in carotenoids (such as lutein, zeaxanthin or beta-carotene) is known to enhance several aspects of immune function in the body.

More than 600 carotenoids exist in plants' These pigments are responsible for the bright yellow-orange and red colors of many of the commonly eaten fruits such as mango, citrus, peach, pineapple, tomato, strawberries, apricots, guava, watermelon, and cantaloupe, and vegetables such as carrots, squash, pumpkin, and sweet potato. Dark-green leafy vegetables are also rich sources of carotenoids, but the bright-green chlorophyll pigment masks the yellows and reds.

In addition to carotenoids, fruits and vegetables are rich in vitamin C, folic acid, and other protective substances such as plant sterols and protease inhibitors. Plant sterols, such as ß-sitosterol and stigmasterol, significantly decrease the incidence and growth of colon tumors that are chemically induced in animals. Some protease inhibitors in legumes may also suppress the initiation and promotion of cancer.

Whole Grains

Whole grains are also rich in phenolic compounds such as ferulic acid (a phenolic acid commonly found in whole grains) as well as other health-promoting phytochemicals such as flavonoids, lignans, phytosterols, phytates, and tocotrienols. In the Nurses' Health Study, the risks of coronary heart disease, of stroke, and of type 2 diabetes were reduced about 30-40 percent in those who had the highest intake of whole grains.

Recently, it was observed that a high intake of whole grains was associated with a 20-50 percent reduction in the risk of cancer. Those who had the highest intake of whole grains were also shown to have a 25 percent reduction in all causes of death. Because 90 percent or more of the phytochemicals in grains are in the bran and germ portion of the kernel, it is important to eat grains that are unrefined. (The refining process removes the bran and germ portions, leaving only the primarily starchy endosperm.)

Plant Foods are Winners

The National Cancer Institute has identified about three-dozen plant foods that possess cancer-protective properties. The foods and herbs with the highest anticancer activity include garlic, soybeans, cabbage, ginger, licorice root, and the umbelliferous vegetables (including carrots, celery, cilantro, caraway, dill, 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 bell peppers), brown rice and whole wheat. Other foods and herbs that were found to contain a measure of anticancer activity included oats and barley, mints, rosemary, thyme, oregano, sage, basil, cucumber, cantaloupe and berries.

Phytochemicals are not evenly distributed in plants. They are usually more concentrated in the outer portions. For example, the outer leaves of lettuce contain from 60 to 460 mg/kg of the flavonoid quercetin, while the inner leaves, protected from the sun, contain about 3-8 mg/kg. In a similar way the flavonoids are concentrated in the skins of fruit. Phloridzin is found at levels of 80-420 ppm in apple peel while the pulp only has 1620 ppm of phloridzin. In whole wheat, ferulic acid levels are reported to be 490521 ppm, while refined wheat has only 38-44 ppm. Clearly, the bran and germ contain most of the phenolic acids such as ferulic acid.

Citrus are Terrific!

Some plant foods are really loaded with a variety of phytochemicals. For example, an orange (and other citrus fruits are similar) has about 150 phytochemicals altogether. There are 60 flavonoids present.

These compounds activate the P-450 enzyme system that helps eliminates cancer-causing substances, and inhibit tumor cell growth. The 40 liminoids that provide the bitter flavor are known to stimulate glutathione-S-transferase (GST), a phase II enzyme that helps to eliminate cancer-causing agents from the body.

The 20 carotenoids in citrus stimulate the immune system as well as protect against age-related macular degeneration. The glucarates, which are found in the albedo (the white skin-like portion underneath the peel), are protective against breast cancer. The glucarates significantly reduce the incidence and multiplicity of mammary tumors, and increase tumor latency (delay appearance of tumors). And finally limonene, a terpenoid in the peel (and some of this may enter the orange juice in the industrial juicing process) protects against cancer.

Safe Under the Umbrella

A number of protective mechanisms have been suggested for the action of phytochemicals. Most of them are antioxidants, and act as free radical scavengers. The carotenoids stimulate immune responses and are known to regulate gene expression (connexion43). The sulfur compounds in garlic and onions stimulate beneficial DNA repair while ellagic acid, liminoids, isothiocyanates, sulfides, curcumins, and phthalides all induce GST, the Phase II enzyme which helps to detoxify and eliminate cancer-causing agents from the body. Various indole compounds present in cruciferous vegetables also activate the enzyme benzopyrene hydroxylase that degrades carcinogens.

In preliminary studies resveratrol, a substance found in red grape skins, has been shown to reduce the risk of breast, colon and liver cancers. Scientists have shown that compounds in grapes inhibit breast cancer by suppressing the estrogen-producing enzyme aromatase. Oilseeds, such as sesame seed and especially flax seed, are very rich sources of lignans. Plant lignans are converted to mammalian lignans (enterolactone and enterodiol) by bacterial fermentation in the colon. The lignan metabolites have a structural similarity to estrogens and can bind to estrogen receptors and inhibit the growth of estrogen-stimulated breast cancer.

Fruit and vegetables along with many of the culinary herbs contain terpenoids, which have anti-cancer properties. Rosemary, sage, oregano, thyme and other flavoring herbs that belong to the Labiatae family are known to possess strong antioxidative activity. For example, rosemary and sage contain substantial levels of carnosol and ursolic acid, potent antioxidants that possess anti-tumor activity. Ginger contains a dozen phenolic compounds, known as gingerols and diarylhaptanoids that have potent antioxidant activity. The terpenoids are responsible for the unique flavors of many common herbs and seasonings. These compounds inhibit cholesterol synthesis and act as cancer-chemopreventive agents. (see Table 2)

Getting More Phytochemicals

There are four ways by which we could increase our intake of phytochemicals. Firstly, we could consume more foods that are rich in phytochemicals (see Table I). Secondly, we could fortify our foods with phytochemicals. But, which substances would we add? And how effective would this fortification be? At present we have no data to show the validity of this procedure. We could also develop crops with a higher phytochemical content. But the extra phytochemicals would cause the foods to have a bitter flavor and stronger taste.

Fourthly, we could get our phytochemicals as a supplement. The physiologically-active com-ponents of food can be extracted and formulated into supplements, called nutraceuticals. These supplements are used to deliver a concentrated form of a bioactive agent from food, presented in a non-food matrix. They are often used to enhance a person's health. The dosage level of nutraceuticals usually exceeds that found in normal food. At the present time, we are not sure if these nutraceuticals are safe or effective.

If we are thinking about getting our phytochemicals from nutraceuticals rather than from foods there are some issues, which need to be addressed. Unlike many vitamins, phytochemicals have extended families. For example, there are scores of related flavonoids at different levels in various foods and these flavonoids have different biological activities. They exist both with sugar units attached and without sugars (i.e. glycosides or aglycone forms). The glycosides may have one or more sugars attached to the flavonoid. How well is each of these forms absorbed? And do they act synergistically? We don't know. And, have all of them been discovered, or are there more nutritional foods still unknown?

What About Bioavailability?

Then there is the question of bioavailability. We know that the efficiency of carotenoid absorption is determined by a number of factors such as the food matrix, food processing, structural differences in carotenoids (whether they are oxygenated or not), and interactions with other food components.

The availability of carotenoids from vegetables shows quite a wide variation. Two-thirds of the lutein is available from mixed vegetables while only forty-five percent of the lutein in spinach is avail~ able. There is also a wide bioavailability of beta-carotene from the various vegetables. One experiment revealed that 4 percent of the beta-carotene was absorbed from spinach, 14 percent from mixed vegetables, 21 percent from carrots, 74 percent from broccoli, and 96 percent from green peas. Furthermore, there is a greatly enhanced bioavailability of carotenoids when the vegetables are homogenized and heated. The carotenoid pigments in carrots, spinach, and tomatoes have shown a two- to five-fold increase in availability when the vegetable is liquit1ed and heated.

Some have asked, "Why not give people beta-carotene supplements rather than trying to get them to eat foods rich in beta-carotene?" The beta-carotene supplements should increase serum levels and lower the risk of cancer. However, in half-a dozen large randomized cancer prevention trials, lasting 4 to 12 years, that involved feeding subjects 20 to 50 mg/day of beta-carotene, there was actually observed a 10 to 50 percent increase in the risk of cancer-the very opposite of what was expected!

While the antioxidant vitamins C and E and beta-carotene apparently have a low toxicity, and may act synergistically, the health benefits and safety of a regular and long-term intake of antioxidant supplements is questionable. Preliminary data has been negative so far, and we await further results from large-scale intervention trials. On the other hand, the regular consumption of plant foods that are naturally rich in those vitamins, carotenoids and other antioxidants is associated with substantial protection against heart disease and cancer.

Lycopene: It's Red All Over

Lycopene is the red pigment in tomatoes, strawberries, and other red produce, which is protective against heart disease and prostate cancer. In the Adventist Health Study, men who consumed tomatoes more than 5 times a week had a 40 percent lower risk of prostate cancer compared with those men consuming tomatoes less than once a week. In the Health Professionals Study the risk of prostate cancer was 22 percent lower and 35 percent lower in those men consuming 4 to 7 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.

Tomato products apparently deliver more lycopene than raw tomatoes, since the processing of tomatoes has a significant effect upon the availability of lycopene. For example, heat processing induces isomerization of all trans-lycopene to cis-isomeric forms, which have greater bioavailability. Food processing also breaks down cell walls and weakens bonds between lycopene and the food matrix.

Should we get our lycopene from food or supplements' Are lycopene supplements safe and effective' Dietary supplementation of lycopene does not seem appropriate at this time. Information is lacking for the potential health risk reductions, mechanisms of action, and dose-response relationships for lycopene. Additional data is needed to determine whether the utilization of lycopene is better or worse from supplements compared with food.

Choices About Garlic

The use of garlic is associated with cholesterol reduction, decreased blood clotting, immune enhancement, and a lowered risk of cancer. But which form of garlic should be used' Tablets, capsules, tincture, or aged extracts? Garlic supplements are variable in their effectiveness and depend upon the type of preparation used. Garlic contains numerous sulfur and other active compounds. Do these compounds act synergistically? We don't know. Using garlic cloves seems to be a safer way to secure the health benefits of garlic. Also, there is some experimental evidence that cooked garlic is more effective than raw.

Soy Isoflavones and Blood Lipids

A meta-analysis of 38 controlled clinical trials by Dr. Anderson involving an average soy protein intake of about 50 grams a day revealed that the soy intake was associated with decreases of about 10 percent in total and LDL cholesterol and triglyceride levels. People have wondered whether the same effect could be seen with capsules of soy isoflavones. According to a number of studies there appears to be no effect of feeding isoflavone supplements on blood lipid levels. For example, middle-aged adults with normal cholesterol levels who took a 55 mg isoflavone supplement every day for 8 weeks experienced no changes in their blood lipid levels-either the LDL cholesterol or triglyceride levels.

P.J. Nestel and associates provided 21 perimenopausal/ menopausal women with 80 mg isoflavones per day, containing 45 mg genistein, for 5-10 weeks in a placebo-controlled, crossover trial. While arterial elasticity was seen to improve in the women, their plasma lipids were unaffected. It appears that a protein matrix is necessary for the isoflavones in the soy to lower blood lipids. Other factors in soy protein, which should be considered as active agents to lower blood lipid levels, include the phytosterols and saponins. It should be noted that the isoflavones also require fat for absorption.

Dr. Setchell analyzed 33 brands of isoflavone supplements and found that the total isoflavones per serving varied greatly from 0-58 mg. The measured amount of isoflavone was, on average, 72 percent of that claimed on the label. The source (soy germ, soy isolate, red clover, kudzu) determined the relative amounts of the various isoflavones. Genistein, daidzein, glycitein formononetin, and biochanin A occurred in various amounts, depending on the blend.

Isoflavones can exist with attached sugar molecules (glucosides) or without sugar molecules attached (aglycones). Other groups (such as acetyl or malonyl) may be attached. There is a real need for product quality control and standardization of the isoflavone blends. The isoflavone supplements make a wide range of claims. Little information exists regarding bioavailability, metabolism, clinical effectiveness, and safety of the isoflavone supplements. According to Setchell, there is always the danger of toxicity from overdosing with supplements.

Choose Your Dose Properly

Dosage is also a very important element. A number of culinary herbs that are rich in essential oils provide health-promoting effects. The terpenoids inhibit cholesterol synthesis, and provide protection against cancer and cardiovascular disease. However, large amounts of the extracted oils can be very toxic. Many of the monoterpenes (cineole, anethole, camphor, menthol) can be toxic at high doses. Clearly, if we are taking extracts of plants that have highly concentrated levels of phytochemicals, we run the danger of ingesting toxic levels. An old adage says that the difference between useful therapy and toxicity may be simply one of dosage!

Issues to Resolve

Clearly, there are a number of unresolved issues regarding the use of phytochemicals supplements or concentrates. These need further researching. They include the following 12 issues:

• What are the factors that affect the stability and the bioavailability of phyto-chemicals and their different forms? What influence does food processing have?
• What food matrix is needed for effective absorption?
• Which isomers (look-alike relatives) are the most active?
• What is the effective dose of phytochemicals that provides health benefits?
• Is there a dose-response relationship for the phytochemicals, that is, does the effect increase with amount used?
• What is the metabolic fate of the absorbed phyto-chemicals and what happens to them in the process of digestion and the physiological activity of the products'
• How do phytochemicals act in specific tissues?
• What amount of phyto-chemicals
• causes adverse or toxic effects?
• Are there synergistic (combined) effects between any of the phytochemicals or with the food'
• Is there any subject variation regarding absorption and body use of phytochemicals?
• Are supplements as effective as food,
• more effective, or less effective?
• How reliable are the label claims regarding contents?

Conclusions

With the wide variety of health-promoting phytochemicals found in fruits, vegetables, whole grains, nuts, legumes and herbal seasonings, the regular consumption of these plant foods is essential for good health and reduction of the risk of chronic disease such as cardiovascular disease and cancer. The safety and effectiveness of consuming concentrated extracts of vegetables and fruits (nutraceuticals) that contain very high levels of phytochemicals are unknown at this time. Clinical trials examining the physiological effects of lycopene, beta-carotene, isoflavones, phytosterols, tocotrienols, lutein, and other nutraceuticals have met with mixed and sometimes disappointing results.

Table 1

Health-promoting Phytochemicals in Plant Foods

Phytochemical

Allyl sulfides

Carotenoids

Coumarins

Curcumins

Dithiolthiones

Ellagic acid

Flavonoids

Indoles/isothiocyanates

Isoflavones

Glucarates

lignans

liminoids

Phthalides/polyacetylenes

Phenolic acids

Phytates

Phytosterols

Protease inhibitors

Saponins

Terpenes

Tocotrienols

Food Source

Onions, garlic, chives, leeks

Yellow-orange vegetables/fruits; green, leafy vegetables; red fruits

Celery, parsnips, figs, parsley

Turmeric, ginger

Cruciferous vegetables

Grapes, strawberries, raspberries, nuts

Most fruits and vegetables

Broccoli, cabbage, cauliflower, Brussels sprouts, and radish Soybeans, tofu

Citrus, grains, tomatoes, bell peppers

Soybeans, flax seed

Citrus

Caraway, celery, cumin, dill, fennel, parsley, carrots, coriander Berries, grapes, nuts, whole grains

Grains, legumes

Seeds, legumes

Grains, seeds, nuts, legumes

Beans, herbs

Cherries, citrus, herbs

Nuts, seeds