If you saw them listed as ingredients on a cereal box you might be alarmed: isoflavones, terpenes, indoles, phenolic acids. But these tongue-twisters aren't artificial additives, they're naturally occurring chemicals found in foods like fruits, vegetables, and grains - chemicals our bodies may use as part of their disease-fighting arsenals.

These substances are called phytochemicals (phyto is Greek for plants). Some, such as digitalis and quinine, have been used for medicinal purposes for centuries. The anticancer effects of many of them, however, are only beginning to be explored.

Phytochemicals differ from vitamins and minerals in that they have no known nutritional value. Some are antioxidants, protecting against harmful cell damage from oxidation. Others perform different functions that help prevent cancer. Today's laboratory pioneers are still deciphering the many ways phytochemicals in foods may offer front-line defenses against cancer.

Isothiocyanates, for example, found in cruciferous vegetables like broccoli and cabbage, protect against cancer through their effect on enzymes. Saponins, found in beans and legumes, may prevent cancer cells from multiplying by influencing a genetic material in the cells.

A single tomato or orange contains hundreds, and possibly thousands of phytochemicals. Indeed, much of the work thus far has been simply cataloging and classifying them.

Phytochemicals as cancer preventives

One reason scientists are so excited about phytochemicals is their apparent ability to stop a cell's conversion from healthy to cancerous at so many different stages. Indoles, a family of phytochemicals found in cruciferous vegetables, stimulate enzymes that perform many functions One impact is to make the hormone estrogen less effective, possibly reducing breast cancer risk. Research shows that allyl sulfides, in the garlic and onion family, increase enzymes that affect cancer-causing substances and help the body get rid of more of them. And Ellagic acid, a type of phenolic acid found in strawberries and raspberries, reduces the genetic damage caused by carcinogens like tobacco smoke or air pollution. It does this by affecting the carcinogen, and also, possibly, by directly protecting the cell's genetic material.

One scientist who gives a hill of beans - soybeans, that is - about phytochemicals is Stephen Barnes, Ph.D., a pharmacology professor at the University of Alabama at Birmingham. Barnes has spent the past decade investigating the anticancer properties of soy foods.

"We're trying to determine if certain compounds in the soybean are responsible for the lower rates of cancer, particularly breast and prostate, that are seen in people who consume soy as a significant part of their diet," said Barnes.

Tofu, soy milk, and other foods made from soybeans are rich in isoflavones, which may inhibit cancer cell growth and division under some conditions. Since cancer is the result of the cell growth process gone awry, isoflavones may provide a means for switching off the unusual growth

Barnes is currently overseeing two pilot studies he hopes will provide promising evidence for large clinical trials in the future. In one, 37 healthy pre-and post-menopausal women in San Francisco are consuming diets with and without soy. Researchers are examining their breast fluid for properties that may mean greater risk of breast cancer. In the second trial, at the University of Alabama at Birmingham, 40 elderly men with elevated prostate-specific antigen (PSA) levels, which means they may be at risk for prostate cancer, are drinking soy beverages to see if the isoflavones lower the PSA levels.

Phytochemicals in cancer treatment

Phytochemicals are also being studied in cancer treatment, where they are used in amounts so concentrated they qualify as drugs. Pamela Crowell, Ph.D., an assistant biology professor at Indiana University-Purdue University at Indianapolis, has found the perillyl alcohol, found in cherries and lavendar, causes pancreatic tumors to regress in laboratory animals. She says these compounds appear to cause tumor cells to shift to a less malignant type. Perillyl alcohol belongs to a class of phytochemicals called terpenes. Limonene, contained in the peel of citrus fruits, is one of the best known phytochemicals in this class. In laboratory animals it blocks the development of breast tumors and causes existing tumors to regress.

Taxol, another member of the terpene family, is not found in food, but is a phytochemical already being used in clinical trials. The Food and Drug Administration approved the compound, derived from the Pacific yew tree, for treating ovarian cancer in 1992 and breast cancer in 1993. Taxol is now made in a semisynthetic process, so there is no shortage of the drug.

Molecular pharmacologist Susan Band Horowitz, Ph.D., has been studying taxol since the 1970s. It was her laboratory at the Albert Einstein College of Medicine in the Bronx, New York, that first determined how taxol works to prevent cell division. Although it is used in very low concentrations, it does have side effects such as hair loss, says Horwitz. She stresses that people and animals have died from ingesting taxol in its natural state.

Phytochemicals, like many other chemicals, can be toxic and must be properly formulated and tested before using.

Designer Foods Fanfare

Although there's still much that is unknown about phytochemicals, what scientists do know, at least from many human studies worldwide, is that people who eat large quantities of fruits and vegetables have reduced cancer risks. Some researchers are looking at the effects of other aspects of a lifestyle associated with eating lots of fruits and vegetables, like eating less fat or exercising more. Many scientists, however, think a lifelong diet of phytochemicals plays an important role.

Is an anti-cancer cocktail brimming with extra-strength phytochemicals soon to be on supermarket shelves? Many experts predict it won't be long before some of the better-known phytochemicals start appearing in pills or packaged foods the way vitamins, calcium, beta-carotene, and other nutrients are now. Indeed, the National Cancer Institute's (NCI) major foray into phytochemicals was dubbed the Designer Foods Research Project when it was first announced in 1989 by Ritva Butrum, Ph.D., then Chief of NCI's Diet and Cancer Branch, and now Vice President for Research at the American Institute for Cancer Research. Carolyn Clifford, Ph.D., who directs the program today, says the technology is far ahead of the science at this point.

"You can modify the chemical consituents in food through plant breeding, bioengineering, and food processing, but before we get to that stage we need to know: What compounds? What levels are effective?" says Clifford.

In other words, would megadoses of certain phytochemicals really head off cancer? Could they have harmful side effects? Does the preventive punch of phytochemicals depend upon dozens or hundreds of them working together in a complex ballet, as they do in foods?

Seattle-based nutritionist Mark Messina, Ph.D., does not endorse the trend toward souped-up cereals or what might be called "phytamin" pills. "I think we should focus our time on getting people to consume the type of diet we already know will reduce cancer risk. The notion of "designer foods" is in essence trying to supplement your way to good health. It doesn't make up for a bad diet, says Messina, formerly with the NCI and now a nutrition consultant.

Messina, like Barnes, is a big booster of soy foods and recommends Americans eat one serving (1/2 cup of tofu or 1 cup of soy milk) daily for the isoflavones, which aren't readily found in other foods. He says studies have shown that one serving daily is enough to lower cancer risk.

Table:

Phytochemicals: The Next Frontier

Phytochemical Family:

*Food Sources:*
Ally Sulfides	Onions, garlic, leeks, chives
Indoles	Cruciferous vegetables (broccoli, cabbage, kale, cauliflower)
Isoflavones	Soybeans (tofu, soy milk)
Isothiocyanates	Cruciferous vegetables
Phenolic acids	(ellagic acid, Tomatoes, citrus fruits, carrots,
ferulic acid)	whole grains, nuts
Polyphenols	Green tea, grapes, wine
Saponins	Beans and legumes
Terpenes	(Perillyl alcohol, Cherries, citrus fruit peel limonene)

The Take-Home Message

Although cruciferous vegetables and citrus fruits are developing reputations as phytochemical powerhouses, keep in mind that these are simply the most studied foods and scientists are learning more everyday. Eating a variety of vegetables and fruits is more important than concentrating on particular kinds to get the full gamut of phytochemicals found in nature.

Here are some easy ways of increasing your intake of phytochemicals.

Eat more grains. Don't limit your choices to bread, rice, and pasta. Try couscous, quinoa, bulgur, barley, kasha, and wild rice for variety. Once available only in health foods stores, most of these grains have become supermarket staples.

Eat a variety of vegetables. Broccoli is very nutritious, but you don't have to eat it every day. Don't forget carrots, cauliflower, greens, winter and summer squashes, green and red peppers, snow peas, red cabbage,... the list is endless. Bags of mixed vegetables in the frozen foods section make getting an assortment at a single meal easy. Don't feel you have to eat a wide variety every day; your weekly consumption is what's important.

Eat more fruits. Research shows the average American eats about one serving a day. A glass of juice at breakfast is nice, but how about some bananas, blueberries, or peaches atop your cold or hot cereal? A crisp apple or fragrant orange as a midday snack or perfectly ripe strawberries for dessert?

Don't forget herbs and spices. Even though you don't eat much of them, they contain phytochemicals too. Garlic, hot peppers, basil, parsley, and other fresh and dried herbs add zip to low-fat foods.

Decrease portion size of meat, fish and poultry. You'll naturally eat more grains and vegetables if you do. Remove half the filling from an overstuffed deli sandwich. Update a favorite dish by changing the meat-to-vegetable ratio: chicken and pasta casserole with peas can become pasta and pea casserole with chicken.

Explore new foods and new recipes.

Tofu may be a phytochemical-filled option, but how to prepare it may be a challenge. The same may be true for other unfamiliar offerings in the produce department, like jicama, fennel, tomatilloes, daikon, papaya, or passion fruit. Some supermarkets offer recipe cards or fliers to encourage customers to try the more exotic fare. Or check out one of the many new low-fat healthy cookbooks for tips.

"Five years ago we didn't know about half the phytochemicals we know of today; five years from now we'll know about that many more," says nutritionist Mark Messina, Ph.D. "I think the bottom line with phytochemicals is that they just give us more reasons to consume a plant-based diet."

1. Edited by Thomas Dao, M.D.; Jan Kasofsky-Flynn, Ph.D., R.D.; Adrianne Rogers, M.D.; David Rose, M.D., D. Sc., Ph.D.; Karen Collins, M.S., R.D.; Melanie Polk, M.M.Sc., R.D., L.D.; Reprinted with permission from the American Institute for Cancer Research, 1759 R Street, NW, Washington DC 20069.

References: 1. American Institute for Cancer Research Newsletter, "Foods `Designed' to Prevent Cancer," Spring 1992, Issue 35; "Green Tea: Drink to Your Health?" Spring 1993, Issue 39; "Linking Plants to People," Winter 1995, Issue 46. 2. Berkowitz, Kathy Field, "Will `Designer Foods' Fortified with Phytochemicals Fight Cancer?" Environmental Nutrition, March 1993, pp. 1-2. 3. Interviews with: Stephen Barnes, Ph.D., University of Alabama at Birmingham; Carolyn Clifford, Ph.D., National Cancer Institute; Pamela Crowell, Ph.D., Indiana University-Purdue University at Indianapolis; Susan Band Horwitz, Ph.D., Albert Einstein College of Medicine, Bronx, NY; and Mark Messina, Ph.D., Port Townsend, WA. 4. Schardt, David, "Phytochemicals: Plants Against Cancer," Nutrition Action Healthletter, April 1994, pp. 1-4.

[as published in the VHL Family Forum, March 1996]

As published in the VHL Family Forum, 4:1, March 1995. For permission to reprint, please contact the VHL Family Alliance, editor@vhl.org. Further information is available from the VHL Family Alliance, info@vhl.org.