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FOOD AS MEDICINE: TAKE TWO BROCCOLI FLORETS AND CALL ME IN THE MORNING

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We know how you feel about vegetables. You used to push them strategically around your plate, then secretly feed them to the dog. Now that you're grown up you obediently trudge to the salad bar, then load up with cottage cheese and croutons.

But here's the awful truth: Vegetables may be even better for you than your mother said. They may even protect you from cancer and heart disease.At least that appears to be the conclusion of hundreds of studies conducted in laboratories around the world as scientists explore the newest dietary frontier.

Vegetables are not only more important than we thought, they're also more complicated. They contain not only vitamins and minerals and carbohydrates and fiber, but also compounds known as phytochemicals (a fancy but fairly meaningless word meaning simply "plant chemicals").

The names of these phytochemicals hardly roll off the tongue - isothiocyanate, glycyrrhizin, beta-cryptozanthin. There are hundreds of thousands of them, most of them discovered only in the past five years.

They're not vitamins. They aren't nutrients crucial in keeping people alive. But they are biologically active.

In the plants themselves, these chemicals fight off predators. Now, in labs from Provo to Tokyo, scientists are trying to understand what they do for humans. But as one researcher at a lab at the University of Illinois says, "we're still in the dark ages."

We know that people who eat more vegetables and fruits have fewer chronic diseases than those who eat less. We know a little bit about which particular fruits and vegetables seem to offer protection from certain diseases. We know about what some of the phytochemicals in vegetables and fruits can do in petri dishes and, in some cases, in animals.

We suspect that phytochemicals can protect humans from the worst of diseases. We don't know for sure, though, how that might happen. Research results are intriguing but sketchy, and in some cases contradictory.

But that hasn't stopped us from being hopeful. We search, as always, for a magic bullet, and hope to find it - even in broccoli. Or, better still, in a broccoli pill.

If you want to get a handle on just how promising and complex the phytochemical revolution is, take a look at the maroon carrot.

Actually you won't be able to see the maroon carrot at your supermarket till next winter. But Leonard Pike, a horticulturist at Texas A&M University, is happy to talk about it now.

Pike runs the university's Vegetable Improvement Center, a name that evokes all the ambivalence - the disdain and guilt and grudging respect - that Americans feel about vegetables.

Pike knows the statistics: that the average American eats three or fewer servings of vegetables and fruits a day, even though the government encourages at least five servings a day. So Pike and his colleagues toil to come up with vegetables that people will actually eat - ones that are tasty and pretty and take advantage of the emerging research about phytochemicals.

The lab works both with medical researchers and with the food industry, trying to develop foods that contain more of the compounds that might fend off tumors and heart attacks

Their first product is the maroon carrot. Beet-colored on the outside, it is crunchier and sweeter than the average carrot. Teenagers who visit the lab gravitate toward it.

The maroon carrot has also been engineered to provide about twice the amount of beta-carotene as a garden-variety carrot.

Beta-carotene belongs to a class of phytochemicals known an carotenoids, a class that includes about 600 naturally occurring compounds. In human blood, beta-carotene is the most widely occurring carotenoid. It has also gotten the most press of any phytochemical.

In the beginning, all the press was good: study after study that seemed to prove that a diet rich in the antioxidant beta-carotene reduced the risk of cancer and heart disease. And then in 1994 there was a disturbing report out of Finland.

Over 29,000 male smokers, ages 50 to 69, were studied for six years. Some were given vitamin E, some beta-carotene, some a combination, some a placebo.

The results: the incidence of lung cancer was 18 percent higher in the men receiving the beta-carotene.

A similar trial in the United States - following 18,000 people at high risk for lung cancer - was halted after participants supplemented with beta-carotene had 28 percent more lung cancer and 17 percent more deaths than the placebo group.

About the same time, a third study - the Physician's Health Study - followed 22,000 male doctors and discovered that beta-carotene supplements provided neither any benefit nor any harm when it came to either cancer or heart disease.

On the other hand, an animal study, published in 1995, found this: That of hamsters induced with oral cancer, those that had a diet rich in beta-carotene developed fewer precancerous cells and fewer, smaller tumors.

Scientists around the world are still scratching their heads.

"I don't think anyone really understands what happened in those (Finnish) trials," says Michael Wargovich, a researcher at the University of Texas M.D. Anderson Cancer Center.

The assessment is difficult because humans are complex. Unlike rats or hamsters, one person isn't like another. We each are subject to so many variables, from diet to genetics to environmental exposure.

And phytochemicals are equally as complex. In one circumstance they may prevent disease and in another they may cause disease. Cabbage, for instance, has been shown both to cause tumors in animals and to prevent them.

Even more important, says Wargovich, they may not do their magic alone.

Carrots, for example, contain dozens of phytochemicals, whereas the supplements given to the Finnish smokers contained only beta-carotene. "My suspicion is that it's the synergy that's protective," says Wargovich.

Alone, each phytochemical may be useless; it may take all the other phytochemicals that make up any particular vegetable or fruit, working together, to help prevent disease.

In addition, notes nutritionist Pat Montague of Nature's Way, if you heavily supplement with one carotenoid you may become deficient in others.

Clearly, if phytochemicals are the new frontier, we haven't even set off in the handcarts yet.

So, what do we know for sure?

The first studies that intrigued scientists were broad population studies comparing disease rates in various countries around the world. For example, breast cancer mortality rates per 100,000 women are 4.6 in China and 22.4 in the United States.

Epidemiologists studied these kind of findings and discovered that the lower cancer and heart disease rates occurred in countries where people consumed more fruits and vegetables.

Later they did diet surveys in individual countries and discovered, again, that the people who ate more fruits and vegetables had lower rates for all types of cancer and for heart disease. Then they began honing those results. What exact fruits and vegetables? Which exact chemicals in those fruit and vegetables?

They asked people what they ate. They examined vegetables under microscopes. They took, for example, stalks of broccoli, put them in a blender, extracted different chemicals and examined, in a petri dish, what those chemicals did to certain cancer-fighting enzymes.

They tested the compounds on rodents that had been injected with carcinogens. Lately they have also begun "feeding trials" in which they test certain vegetables and fruits on human subjects.

Here are some of the most interesting results:

- Total vegetable and fruit intake: A 20-year Harvard study of middle-aged men found that the risk of stroke (adjusted for age) decreased in proportion to the amount of fruit and vegetables eaten. For each increment of three servings per day, there was a 22 percent decrease in the risk of all types of stroke.

- Tomatoes contain lycopene, a carotenoid believed to be twice as potent as beta-carotene in its antioxidant properties (lycopene is also found in red grapefruit). Three studies point to lycopene's possible health benefits:

Rats fed a high lycopene diet in a Japanese study showed a significant suppression of mammary tumor development.

A diet study in Italy showed less incidence of cancer, most notably gastrointestinal, in people who ate more tomatoes and tomato products.

A Harvard study of over 47,000 men found that those whose diets were highest in tomato sauce, tomatoes, pizza (and strawberries) had lower rates of prostate cancer.

- Broccoli contains about 30 phytochemicals, most notably sulforaphane, a compound shown to reduce mammary cancer formation in rats. A Johns Hopkins study, performed in the Brassica Chemo-Protection Laboratory run by Paul Talalay and his colleagues, found that rats injected with carcinogens developed fewer and smaller tumors if they had been fed sulforaphane.

It appears, says Talalay, that the sulforaphane activates phase II enzymes that can detoxify carcinogens. "It's important, though, that we don't give any impression that this is a treatment," he says. Talalay and his colleagues are planning human studies on tumor formation. "It's a very long term proposition," he cautions.

Other cruciferous vegetables - kale, cauliflower, cabbage, etc. - also contain high amounts of these chemicals.

- Spinach and collard greens contain lutein and zeaxanthin, which seem to protect against age-related macular degeneration that can lead to blindness. A Harvard study found that a diet higher in green leafy vegetables was associated with a lower risk of this form of blindness. Those people who ate the most spinach and collard greens had a 43 percent lower risk for the disease.

- Citrus fruits contain, among other things, liminoids. They appear to inhibit a variety of tumors in animals, both spontaneous and chemically induced, at various sites, including mammary, skin, liver, stomach and lung.

- Garlic, one of the most studied foods, contains several phytochemicals that may play a health role.

An analysis of five controlled clinical trials, published in the Annals of Internal Medicine in 1993, reported that "the best available evidence suggests that garlic, in an amount approximating one-half to one clove of garlic a day, decreased total serum cholesterol levels by about nine percent. . . ."

The Iowa Women's Health Study of over 41,000 women studied participants for five years and concluded that those ingesting more than one serving of garlic per week cut their risk of colon cancer by one-half.

In cell cultures, according to Byron Murray of Brigham Young University, one particular sulfide in garlic prevents a protein in cancer genes from getting to the site where it can become active. This protein, says Murray, is found in 50 to 70 percent of human tumors.

The Garlic Hotline at the Cornell University Medical Center in New York City reports that it gets an average of 100 calls a day from people wanting to know more about garlic's effect on health.

- Soy contains isoflavones, such as genistein, which seem to fight cancer at several stages and at several sites in the body. It also seems to reduce the levels of serum cholesterol. (See story on C1.)

For all their promise, however, none of these studies, or hundreds like them, definitively proves anything. We still can't say for sure that a particular food protects us from cancer, and what exactly it is about that food that might be beneficial.

"A great deal of what people say in this field is hype," says Johns Hopkins' Paul Talalay. And the questions people ask most often, he says, "we don't have answers for."

People want to know, for example, how much of a vegetable they should eat.

But, notes Talalay, not all broccoli is created equal, and it doesn't come with a label that lists the amount of sulforaphane it contains. Variations in growing and harvesting conditions make a difference. And you can't rely on animals studies to give you a clue about doses, since a mouse, for example, will typically eat 25 percent of its body weight a day.

We also can't assume that if some is good, more is better. "Everything has a toxic point," says Clare Hasler, director of the Functional Foods for Health program at the University of Illinois.

Scientists also don't know enough yet about how we should eat our vegetables. Studies are only beginning on how cooking affects different chemicals. Some compounds are rendered nearly useless when they're heated. Others (such as some chemicals in carrots) are more effective.

In Byron Murray's lab at BYU, a graduate student tested raw and cooked broccoli's ability to retain sulforaphane. Boiling was the worst way to prepare broccoli, but the amount retained also depended on which part of the broccoli was eaten.

Testing different broccoli parts for their effectiveness in inducing the special enzymes that help detoxify carcinogens, the lab found that: a raw 2-inch spear with floret can induce 760 units of the enzyme; a raw floret alone can induce 1580 units; the stem alone 278. Boiled for five minutes, the spear's number of usable enzymes was down to 90 units.

On the other hand, another class of chemicals found in broccoli - indoles - seem to work better when heated.

Our confusion about phytochemicals, though, hasn't stopped the nutritional supplements and food industries from trying to cash in on what little we do know.

"The No. 1 food trend is the increasing role of food and food ingredients in self-medication and disease prevention," trumpeted the July 1994 edition of Food Technology, a publication of the Institute of Food Technologists.

So at the Vegetable Improvement Center at Texas A&M they're working on the Super Onion and the Super Garlic, extra-fortified with phytochemicals like allyic sulfides. Other labs, many of them funded by the foods industry, are testing concoctions such as broccoli-flavored salsa and chocolate-flavored broccoli juice.

Some people call them pharmafoods or nutraceuticals or foodiceuticals - all names that point to the increasingly fuzzy line between food and medicine.

"The food/drug interface" is what Hasler of the Functional Foods for Health program at the University of Illinois calls it. Hasler was in Park City last month at the aptly named "Foods as Medicine" conference.

If you add enough extra beta-carotene to a carrot, does the carrot become a drug? Can you make a health claim about a food? These are the kinds of questions food industry lawyers are grappling over with the Food and Drug Administration (a name that suddenly takes on new meaning).

Quaker Oats is currently in negotiations over its proposed health claim about oat bran and cholesterol. A drug requires two well-controlled clinical trials to be approved, says Hasler. "Oat bran has 17 positive clinical studies but the claim is still pending."

In the meantime, nutritional supplement companies are coming out with what some people are calling "phytamins." There is, for example, the "Cruciferous Vegetable Blend" on sale at New Frontiers. The box pictures broccoli and cabbage, and promises 100 mg of standardized sulforaphane, "400 times as concentrated" as the amount in 3.5 ounces of fresh broccoli.

There are also lycopene pills and a multicarotene pills, and within the next few months at least 10 companies are coming out with pills chock full of isoflavones.

And so another human fantasy is achieved: vegetables you don't have to actually chew or taste. But will pills alone protect us from tumors and heart attacks?

Not likely, say researchers.

"You can't put all the phytochemicals of broccoli into a capsule," cautions Hasler. "The evidence is still in support of whole foods," and variety is the key. There is, she says, no magic bullet.

And we can't be sure, yet, if we're helping or hurting our body by ingesting huge amounts of isolated phytochemicals.

It looks like you still need to eat your vegetables.