Designer foods.

Herbert F Pierson has a 9'x 10' office, a 1972 volkswagen bug, and one-eighth of a secretary. Herbert F. Pierson could revolutionize the American food supply.

In 1989, the National Cancer institute toxicologist came up with what he calls "a small interesting project I wanted to build a career around." Pierson's idea: identify the naturally occurring constituents of fruits, vegetables, and grains that protect against cancer, and add known quantities of them to foods that don't have reliable amounts ... or any.

Voila! Designer foods.

It's too early to know whether Pierson's idea will work, or even whether it will survive the government bureaucracy. But one thing is dear: his small interesting project has captured the imagination of scientists and food companies alike.

Q: What led you to study plants?

A: We spent several years looking at the literature on diet and cancer. We decided not to focus on fiber, fat, or the vitamins that were already being studied. instead, we wanted to know what else in food might be contributing to the effect of diet on cancer.

We noticed that populations consuming green leafy vegetables, orange yellow vegetables, fruits, and grains had protection against cancer. So we started looking at the chemical constituents of these edible plants-not at the proteins, fibers, or fats, but at the small organic molecules that have roles in the plants' physiology.

Q: What kind of roles?

A: Some of these substances, which are called phytochemicals, protect against fungal or bacterial infections. Others make the plant more-or less--appetizing to plant-eating animals.

The question is: do these phytochemicals have roles in humans that enable them to protect us against cancer?

Q: Why would you expect them to?

A: In studies where animals are given large doses of powerful chemical carcinogens, many of the phytochemicals showed potent anti-carcinogenic activity. And many of them have subtle drug-like activities or influence human biochemical pathways in favorable directions.

Q: What are some examples?

A: There are at least 500 known carotenoids, of which beta-carotene is the most famous. There are terpenoids, which impart flavors and odors to foods. And then there's a variety of polyacetylenes, flavonoids, coumarins, phenolic acids, glucarates, and limonoids, just to touch on a few.

Q: Why not study whole foods instead of their chemical components?

A: We could if we knew for certain that the phytochemicals were in the foods. But we don't know: there is tremendous variability in foods. It's partly due to agriculture, partly due to genetics, partly due to environmental conditions, and partly due to food processing.

So we came up with the idea of formulating foods with known amounts of these phytochemicals. We call them "designer foods."

Q: Have you created any yet?

A: No. We're still searching for the phytochemicals to formulate into a designer food. In the first year, we'll be looking at phytochemicals in five plants: garlic, licorice root, flaxseed, citrus fruits, and umbelliferous vegetables, which include parsley, carrots, and celery, as well as some of the most toxic plants we know.

Q: How did you pick garlic?

A: It's been eaten by humans for thousands of years, and there was epidemiological evidence showing protection against cancer.

And in animal and cell culture studies, garlic compounds stimulate the biochemical pathway involving glutathione, which detoxifies foreign materials. Garlic compounds also intercept activated carcinogens before they attack DNA.

Q: Why citrus fruits?

A: They also have phytochemicals that prevent cancer in animals.

Flavonoids, for example, enhance the body's detoxification system. They protect cell membranes because they're antioxidants. Flavonoids also help regulate enzymes that go unchecked when a cell becomes malignant.

Q: How are enzymes involved in cancer?

A: When carcinogens or viruses activate a cell's cancer-producing oncogenes, those genes start making proteins, many of which are enzymes that control cell division. When the enzymes are overproduced and underregulated, the cell starts proliferating.

Q: What else is in citrus fruit?

A: Phenolics neutralize carcinogens like nitrosamines. They also stimulate the synthesis of glutathione, the body's detoxifier.

The carotenoids are good quenchers of oxygen free radicals that cause damage.

Saponins and triterpenoids inhibit breast cancer in rodents. The mechanisms are not yet understood, but some researchers believe that saponins block cells' receptors for estrogen.

Q: Why would blocking estrogen inhibit cancer?

A: Estrogen encourages some breast tumors to grow. Saponins and triterpenoids could work like the drug tamoxifen, which is given to many women with breast cancer. Tamoxifen keeps breast cells from absorbing estrogen. But we don't know if saponins and triterpenoids block estrogen receptors in humans yet.

Q: What is flaxseed?

A: It's linseed, and it's one of the few foods that are rich in alpha-linolenic acid, which is one of the omega-3 polyunsaturated fatty acids similar to those in fish oil.

Flax also has a series of phenolic compounds called lignans. Lignans have anti-estrogenic activity, and they're found in high quantifies in the urine of vegetarian women, who have a very low risk of developing breast cancer.

Q: Is licorice root in licorice candy?

A: No. Licorice root comes from a legume, like soybeans. In Europe, it's used in a variety of foods as a flavoring, a stabilizer, and an antioxidant preservative. Some Scandinavian candies contain up to 16 percent licorice root extract by weight.

Q: What's in licorice root?

A: Many international patents have been approved for licorice root's medicinal uses. For example, its constituents have a natural antibiotic activity against Streptococcus mutans, the bacterium that causes dental cavities. You'll see some components of licorice-root-like molecules in mouthwashes.

Licorice root's triterpenoids and some of its phenolics inhibit the key enzymes that are overproduced in cells that are undergoing conversion to cancer.

Q: So year one is garlic, citrus, licorice root, flax, and umbelliferous vegetables. How about year two?

A: We're going to look at soybeans in a little more depth. Soybeans, like most legumes, are rich in isoflavones, which inhibit the activity of tyrosine kinase.

The kinases are enzymes that tend to be overproduced and that are pivotal to the transformation of normal cells into cancer. Reports from The Netherlands indicate that as certain breast cells become increasingly malignant, the activity of tyrosine kinase increases.

Q: But are isoflavones-or other phytochemicals-in food absorbed into the blood?

A: We don't know yet, but a good deal of literature suggests that they are. Another question is whether they reach high-risk tissues such as the breast. Do they get into the cells that are undergoing the precancerous process? And do they alter the activity of these kinases

We need to know more about the changes-or lack of changes-that go on when healthy humans ingest phytochemicals.

Q: What changes will you look for?

A: Well, there's a lot of evidence suggesting that three biochemical pathways-prostaglandins, steroids, and drug-control cell proliferation, which is linked to cancer.

In our reviews, one prostagiandin, E-2, stuck out consistently as potentially harmful. In every animal tumor, in every cancer cell system, and in every human biopsy of tumors or pre-tumors in which prostaglandin E-2 was looked for, it was overproduced. So prostaglandin E-2 is linked to tumor promotion.

It's also the major pain-transmitting neurochemical in the body. That's why you take aspirin for a headache. Aspirin, which inhibits the production of prosatagiandin E-2, was anti-mdnogenic in some studies. But aspirin's acidity in the gastrointestinal tract limits its usefulness for preventing cancer in whole populations. [Taking buffered aspirin doesn't solve the problem-Ed.]

Q: Do some foods inhibit E-2?

A: Yes. Garlic, licorice root extract, citrus compounds, flax, and a number of umbelliferous vegetables.

Q: My are you studying steroids like estrogen?

A: People who are at high risk for breast and uterine cancer have higher levels of compounds that the body processes estrogen into.

Apparently, estradiol-estrogen's parent compound-can follow two pathways in a woman's body. One inactivates the estrogen, removing it as a stimulator of cell division. The other activates the estrogen, making it more potent and less likely to be excreted.

The trick is to find the phytochemicals-- like indoles in cabbages--that favor the estrogen deactivation-andexcretion pathway and that minimize the activation pathway.

Q: What will drug metabolism tell you about cancer?

A: Some of the same oxidative enzymes in the body that help us process-or metabolize-drugs can actually turn environmental pollutants, food contaminants, and even some substances made by the body, into carcinogens. Many phytochemicals stimulate the biochemical pathways that detoxify and excrete drugs, rather than turn them into carcinogens.

Q: So you'll study prostaglandin, steroid, and drug pathways in people who are fed ordinary foods like garlic?

A: Yes, but understand that garlic itself is a chemical nightmare. For example, if you crush up raw garlic, you get a lot of thiosulfinates-allicin is the predominant one. It's one of the major contributors to garlic's odor, it has antimicrobial activity, and it's unstable.

But if you steam distill garlic, the water will create a different variety of disulfides and trisulfides. One, called ajoene, appears to be a potent prostaglandin inhibitor. In fact, there are Japanese patents on a pain-killer made of ajoene. It may end up being the next generation of over-the-counter nonsteroidal anti-inflamniatory drugs.

If you saute garlic in oil, you increase the formation of vinyl-dithiins. They're bronchial relaxers, and there are patents pending. on their use for asthmatics.

The bottom line is: if you were to look at the phytochemocals in the garlic in processed foods versus raw garlic, you'd see dramatic differences, and we don't know which has the best potential for preventing cancer. So we plan to study several processed forms of garlic and compare the results to raw garlic.

Q: Once you identify the phytochemicals like those in garlic, then what?

A: We'll incorporate them into foods-I can't say which-that are acceptable to the people in the study. But first we'll make sure the foods don't cause indigestion, diarrhea, allergic responses, or intolerances at the levels people will be eating.

Then we'll monitor the foods' impact on steroid, prostaglandin, and drug metabolism. Meanwhile, the FDA will conduct special safety studies in animals.

Q: What problems do you anticipate?

A: We don't know how much of these phytochemicals might create adverse reactions. For example, some of the phenolic acids in parsley and celery irritate the gastrointestinal tract.

We've got animal studies designed to find combinations of phytochemicals that produce the maximum anti-cancer activity at the lowest levels. For example, when garlic is combined with the flavonoids, you may get the same effect at lower-and less irritating-levels.

Q: Will you be using larger amounts of phytochemicals than occur naturally in food?

A: No. Let's say you were to extract one clove's worth of garlic's sulfur compounds and incorporate it into a slice of bread, and ask study participants to eat two slices three or four times a day. You'd be feeding them an extraordinary amount of garlic--and perhaps more frequently--compared to what they would typically be getting. But it's still at food, not drug, levels. However, if you were to take that same amount of garlic and administer one of its compounds, such as diallyl sulfide, in pure form in a gelatin capsule, you'd have a drug, not a food.

Q: Will you test the foods only on healthy people?

A: To start with. Eventually, we'll test the foods in populations at high risk for developing cancer. For example, we'd see whether designer foods could reduce the active estrogen and increase the detoxified estrogen in women at high risk for developing breast cancer.

Q: When will we know if these phytochemicals prevent cancer?

A: That comes much later. You have to start out with high-risk people who are basically healthy, feed them the designer foods, and follow them for years, making sure they keep eating the foods. It's important to get support from the food industry because these studies will be expensive.

Q: How is the industry involved?

A: Most of our food ingredients come from industry through legal agreements. For example, a Japanese and several U.S. firms are supplying the garlic for our initial studies. A major cereal company is going to work with us on phytochemicals in grains. We've had more than 150 food and pharmaceutical companies express interest.

Later on, we'll ask the food industry to mass produce the designer foods for the larger clinical studies.

Q: Are others making designer foods?

A: The Japanese and the Germans are way ahead of us. The German FDA has approved the over-the-counter sale of botanicals for disease treatment and prevention. A Japanese company is selling, in vending machines, designer foods formulated from oriental medicinal plants.

Q: Can you tell us now which foods prevent cancer?

A: Recommendations have to come from the National Cancer institute. I can say that it won't hurt to eat more garlic, to keep your diet varied, and to eat as many fruits, vegetables, and whole grains as you can tolerate.