Beyond beta-carotene.

"Now with carotene">beta-carotene!" boasted boxes of Total cereal and Centrum vitamins.

"Antioxidant nutrients such as Beta Carotene and Vitamins C and E help protect against harmful cell damage," claimed an ad by vitamin giant Hoffmann-LaRoche.

Everyone from the National Cancer Institute to Nutrition Action had taken a comfortable seat on the beta-carotene bandwagon.

Oh sure. All had warned that "something other than the beta-carotene in fruits and vegetables could protect against cancer." But once that handy disclaimer was out of the way, we settled in for a nice wagon ride...until April 15, 1994, when the wagon turned into a roller-coaster.

That's when the by-now-famous Finnish trial announced that smokers who were given beta-carotene supplements had a higher, not lower, risk of lung cancer than smokers who didn't take beta-carotene. The critics let loose.

"The study wasn't relevant to nonsmokers." "The Finns got too little, too late." "It was just a fluke!" Only time will tell who's right.

But meanwhile, a few scientists started to retrace their steps. Maybe, just maybe, it isn't beta, but another of the 40 or so carotenoids in food that protects us against cancer. And some scientists studying eye and heart disease have also started to look beyond beta.

A SURE BETA

It all started in 1981. That's when the respected British journal Nature ran an article entitled "Can dietary beta-carotene materially reduce human cancer rates?"(1)

Until then, many researchers thought that vitamin A could prevent cancer. But in Nature, Richard Peto of Oxford University suggested that scientists had been barking up the wrong vitamin.

The most compelling evidence: smokers with lung cancer reported having eaten fewer orange and green fruits and vegetables than smokers who had avoided lung cancer.

So how did "orange and green fruits and vegetables" get boiled down to beta-carotene?

"Beta-carotene was the most abundant of the carotenoids that the body converts to vitamin A," says Regina Ziegler of the National Cancer Institute. For that reason, researchers already knew how much was in which foods and how to measure it in blood.

But so far, beta-carotene hasn't worked against cancer. Researchers have completed three trials in which people were given beta-carotene to see if it would prevent lung or skin cancer or precancerous lesions of the colon.(2)(3)(4) It didn't.

Only in a fourth study, in China, did beta-carotene--in combination with vitamin E and selenium--seem to reduce the risk of stomach cancer.(5)

The disappointing results haven't surprised Ziegler as much as they have others. "What always concerned me about the beta-carotene theory," she says, "is that whenever researchers looked, green and yellow fruits and vegetables were better than beta-carotene at predicting the risk of cancer. The catch was, no one had looked at other carotenoids."

Nor had they looked at other potential cancer-fighters in fruits and vegetables, like indoles or phenols, she adds.

THE EYES HAVE IT

At first they can see shapes, but they can't see to read. Then things get blurry, and finally they disappear. That's what happens to people with age-related degeneration of the macula, a tiny area in the center of the retina. It's the most common cause of irreversible blindness in people over age 65.

It has no known cause and no known cure. That's why researchers are so bent on preventing it.

But how? In the mid-1980s, they hit on a few clues. In several studies, people who had macular degeneration reported eating fewer beta-carotene-rich fruits and vegetables.(6)

Based on that and other evidence, in 1993 the National Eye Institute launched the "Age Related Eye Disease Study." More than 5,000 people at high risk for blindness are being given 1) beta-carotene, vitamin E, and vitamin C, 2) zinc and copper, 3) all five, or 4) a (inactive) placebo.

But in November 1994, a study by Johanna Seddon and co-workers at Harvard Medical School suggested that carotenoids other than beta-carotene might protect the eyes.

Seddon looked at five different carotenoids when she compared the diets of 356 victims of macular degeneration with the diets of 520 patients with other eye diseases.(7) Why did she go beyond beta? "The dietary database for several potentially effective carotenoids had just recently become available," she says.

The results pointed not to orange vegetables, but to green leafy ones.

"People who ate spinach or collard greens two to four times a week had half the estimated risk of those who ate them less than once a month," she says. "Those who ate them five or more times a week seemed to have even a lower risk."

Green leafy vegetables are rich in lutein and zeaxanthin, two other carotenoids. Only then did another piece of the puzzle fall into place.

Lutein and zeaxanthin form the yellow pigment in the macula. "These yellow pigments can filter out visible blue light, which theoretically can cause photic [light] damage," says Seddon.

Interestingly, in 1992 Susan Hankinson of Harvard Medical School found fewer cataracts in nurses who reported eating lutein-rich spinach, but not beta-carotene-rich carrots.(8)

HEARTS GET BETA

It came as a surprise. In 1991 Harvard researchers conducting the Physicians' Health Trial noticed something unusual about 333 doctors who entered the study after having had angioplasty, a bypass, or other signs of heart disease.

Those who were taking beta-carotene were half as likely as the non-takers to have a "coronary event" like a heart attack.(9) But there were only 27 heart attacks altogether.

"It's possible that the results were due to chance," cautioned Harvard's Charles Hennekens at the time.

Nevertheless, the idea that antioxidants could halt heart disease caught fire. Why? Evidence was mounting that LDL ("bad") cholesterol couldn't invade artery walls unless it was first oxidized.

"The preliminary results from the Physicians' Health Trial got tied together with the finding that beta-carotene can serve as an antioxidant," says Harvard's Meir Stampfer.

At the same time, he adds, "sporadic evidence suggested that fruits and vegetables are associated with a lower risk of heart disease."

Since the Physicians' Health Trial, says Stampfer, "it looks like vitamin E is a better antioxidant than beta-carotene," at least in test tubes.

And, in contrast to vitamin E, there is little evidence that people who get beta-carotene from supplements--rather than food--have a lower risk of heart disease.

"That's an important distinction," says Stampfer, "because fruits and vegetables give you lots of other stuff too."

The Women's Health Study, now under way, may help researchers discern what it is in fruits and vegetables that shields the heart. There's just one catch. It will answer questions about only one carotenoid: beta-carotene.

MAKE IT A MILLION AND ONE

Who knows? Maybe someday we'll know that spinach is good for your eyes, carrots are good for warding off cancer, and tomatoes are good for your heart.

It's just too early to say.

And even if you wanted a supplement with lutein and zeaxanthin for your vision, for example, you'd have trouble finding it. "Lutein is not on the market in the U.S.," says Norman Krinsky of Tufts University. Another carotenoid, lycopene, will soon be sold here, he adds.

There's really only one solution.

"We've heard it a million times," says Harvard's Meir Stampfer. "But all that the evidence on beta-carotene tells you is that fruits and vegetables are good for you."

(1)Nature 290: 201, 1981.

(2)New Eng. Journal of Medicine 330: 1029, 1994.

(3)New Eng. Journal of Medicine 323: 789, 825, 1990.

(4)New Eng. Journal of Medicine 331: 141, 1993.

(5)Journal of the Natl. Cancer Inst. 85: 1483, 1993.

(6)Amer. Journal of Epidemiology 128: 700, 1988.

(7)Journal of the American Medical Association 272: 1413, 1455, 1994.

(8)British Medical Journal 305: 335, 1992.

(9)Clinical Cardiology 16 (Suppl. I): I-10, 1993.

WHERE TO GET WHICH CAROTENOIDS

Here are the best places to get the five major carotenoids. The further along each list you go, the less you get. Your best strategy: eat 'em all...and more.

* Alpha-Carotene: canned pumpkin, carrots.

* Beta-Carotene: sweet potatoes, carrots, apricots, spinach, collard greens, canned pumpkin, cantaloupe.

* Beta-Cryptoxanthin: papaya, oranges, tangerines.

* Lutein and Zeaxanthin(*): kale, collard greens, spinach, swiss chard, mustard greens, red pepper, okra, romaine lettuce.

* Lycopene: tomato juice, watermelon, guava, pink grapefruit, tomatoes.

(*)Until recently, laboratory analyses were unable to separate the two.

Source: Journal of the Amer. Dietetic Assoc. 93: 284, 1993. Chart compiled by Ingrid VanTuinen.

THE BOTTOM LINE

* Eating five or more servings of leafy green vegetables every week may protect your eyes.

* Eating five to nine daily servings of fruits and vegetables--especially orange and leafy green ones--may reduce your risk of cancer and heart disease.

* Carotenoid supplements may not do any good. Scientists don't know which of the thousands of substances in fruits and vegetables are protective.