Vitamin E & fat: anatomy of a flip-flop.

"High-vitamin-E foods, even if high-fat, can prevent heart attacks," declared Dan Rather on the "CBS Evening News" last May 1. "Margarine may be good for a healthy heart," announced the headline in the Los Angeles Times the next morning.

Since 1977, health authorities have been urging Americans to eat less fat to cut their risk of heart disease, cancer, and obesity. All it took was one new study to convince millions of people that two decades" of advice had been turned on its head.

"It's so frustrating when scientists flip-flop," says Nutrition Action reader Hilda Zentner of Rockville, Maryland.

You bet it's frustrating. And this one wasn't even a flip-flop.

THE STUDY

As is often the case, it started with a press release from a major medical journal. This study appeared in the best possible place: the New England Journal of Medicine, which is unsurpassed for its tough publication standards and its ability to attract the media.

Lawrence Kushi and colleagues at the University of Minnesota and elsewhere had examined the diets reported in 1986 by more than 34,000 postmenopausal women participating in the Iowa Women's Health Study.(1)

By the end of 1992, 242 of the women had died of heart disease. The researchers' question: Had those women consumed less (or more) of three antioxidants--vitamin C, vitamin E, or carotenoids--than the survivors?

For carotenoids and vitamin C, no important differences appeared. For vitamin E, the differences were almost too dramatic to believe. Compared to women who consumed less than five International Units (IU) of vitamin E a day from their food:

* women who ate roughly 5 IU to 8 IU a day appeared to cut their risk of dying of heart disease by about 30 percent, and

* women who ate more than 8 IU a day seemed to slash their risk by more than 60 percent.

Oddly, vitamin E supplements didn't seem to lower the risk at all (possibly because few women took them for long enough). Only fatty, vitamin-E-rich foods, like margarine, mayonnaise, and nuts or seeds seemed to protect the heart. That's the "man bites dog" twist that made the story big news.

"For years, the leading message about eating and health has been a simple one: Cut out fat and cholesterol," explained an Associated Press story. "Now the reality is beginning to look considerably more complicated."

THE BIG PICTURE

To most researchers, Kushi's study raises more questions than it answers.

First, there's the inconsistency. "This study actually comes to the opposite conclusion of other similar studies on vitamin E and heart disease," notes Julie Buring, an epidemiologist at Harvard Medical School.

* In the Nurses' Health Study of roughly 87,000 women, only vitamin E supplements--not vitamin E in foods--was linked to a lower risk of heart disease.(2) The 4 "percent lower risk was seen largely in women who took at least 100 IU of E a day for at least two years.

* In the Health Professionals Followup Study of nearly 40,000 men, there was some hint that vitamin E found in food might protect the heart. But almost all of the protection was due to the high levels--at least 100 IU a day--in supplements.(3)

WHY RESEARCHERS WORRY

In Kushi's and the other two studies, researchers "observed" a lower risk of heart disease in people who consumed higher levels of vitamin E in food or supplements.

But, says Buring, "the difficulty

RELATED ARTICLE: THE BOTTOM LINE

* Researchers need far more evidence before they can say whether the low doses of vitamin E in foods can reduce the risk of heart disease, as a recent study concluded.

* So far, few experts advise people to eat more fatty foods to get vitamin E.

* Clinical trials are in progress to determine whether the high doses of vitamin E in supplements can prevent heart disease, as earlier studies suggested. Results are due in five to ten years.

with observational studies is that they cannot show that it's the vitamin E itself that lowered risk. People who take supplements or eat diets rich in vitamin E probably have diets or lifestyles that are different in other ways."

Kushi agrees. "Vitamin E intake could be a marker for something else or for a constellation of things that we didn't measure," he says. For example, the women who consumed more vitamin E could have also taken more aspirin, which reduces heart disease risk.

The question can only be answered, says Buring, by clinical trials that randomly assign people to groups that get either vitamin E or a look-alike but inactive placebo. So far, two are complete: * In the Alpha-Tocopherol Beta-Carotene Cancer Prevention Trial, Finnish smokers given 50 IU of vitamin E a day for five to eight years had no lower risk of heart disease than placebo-takers, though their risk of angina pectoris (chest pain upon exertion) was slightly lower.(4, 5)

* In the Cambridge Heart Antioxidant Study (CHAOS), men or women with heart disease who were given 400 or 800 IU of vitamin E a day for a year and a half had a 77 percent lower risk of heart attack. (The E-takers had no lower risk of dying of heart disease, but the study probably was too short to evaluate death rates.)(6)

Two more studies should yield results in five to ten years:

* In the Women's Health Study, which is headed by Buring, some 40,000 health professionals are taking either a 600 IU vitamin E supplement (from natural sources) or a placebo every other day.

* In the Women's Antioxidant and Cardiovascular Disease Study (WACS), women who already have heart disease are taking either a 600 IU natural vitamin E supplement or a placebo every other day.

These trials are testing vitamin E in supplements, not food. Drawing conclusions without trials is risky. Remember beta-carotene? It appeared to reduce the risk of cancer in observational studies and increase the risk in clinical trials...at least in smokers.

"Beta-carotene surprised us," says Buring. "The lesson we should have learned was that the results we see in observational studies aren't always borne out by clinical trials."

BACK TO THE FAT

Many people who caught glimpses--or secondhand reports--of last May's news never even knew it was about vitamin E. All they heard was the headline: "Mayonnaise and margarine may be good for you."

Too bad they didn't hear what the lead researcher had to say.

"The study didn't really address fat per se," Kushi explains. "We're looking at fat intake now, but we're not done yet." So far, he's not advising people to eat margarine.

Kushi's take on the study: "A little bit of nuts and vegetable oils may be okay, but don't go over-board."

And other foods, like whole grain breads and wheat germ, are also sources of vitamin E that his study linked, though less strongly, to a lower risk of heart disease.

"High-vitamin-E diets tend to be high in plant foods," Kushi explains. "So our results fit with advice to eat more grains, fruits, and vegetables."

NOT READY FOR PRIME TIME

Kushi's study wasn't flawed. It just wasn't ready for prime time. Or, one could say, the public just isn't ready for studies that raise questions instead of providing final answers.

"People shouldn't draw conclusions from any one study," explains Buring. "People have got to get away from thinking that every study translates into action. Like most, this one doesn't."

(1) New Eng. Journal of Medicine 334: 1156,1996. (2) New Eng. Journal of Medicine 328: 1444, 1993. (3) New Eng. Journal of Medicine 328: 1450,1993. (4) New Eng. Journal of Medicine 330: 1029,1994. (5) Journal of the American Medical Association 275: 693,1996. (6) The Lancet 374: 781, 1996.

RELATED ARTICLE: Where to Find Vitamin E

The U.S. Recommended Daily Allowance--or Daily Value--for vitamin E is 30 IU. Except for wheat germ, only fatty foods have more than 1 or 2 IU of naturally occurring vitamin E. A handful of breakfast cereals are fortified with 8 to 30 IU. But if future studies confirm Kushi's findings--rather than those from the Nurses' Health Study and the Health Professionals Follow-up Study--only vitamin-E-rich foods, not supplements or fortified foods, may protect the heart.

Food                                         Vitamin E(IU)
General Mills Total (3/4 to 1 cup)               30(*)
Kellogg's Product 19 (1 cup)                     30(*)
Almonds (3 Tbs.)                                 11
Safflower oil (1 Tbs.)                            9
Kellogg's Complete Bran Flakes (3/4 cup)          8(*)
Kellogg's Low Fat Granola (1/2 to 2/3 cup)        8(*)
Kellogg's Mueslix (2/3 to 3/4 cup)                8(*)
Kellogg's Nutri-Grain (3/4 to 1//4 cups)          8(*)
Wheat gemm, toasted (1/4 cup)                     8
Canola oil (1 Tbs.)                               4
Corn oil (1 Tbs)                                  4
Soybean oil (1 Tbs.)                              4
Olive oil (1 Tbs.)                                3
Peanuts (3 Tbs.)                                  3
Margarine, all except fat-free (1 Tbs.)         1-2
Mayonnaise, full-fat (1 Tbs.)                     2
Peanut butter (1 Tbs.)                            2
Bread, whole wheat (2 slices)                     1
Broccoli, cooked (1/2 cup)                        1
Brussels sprouts, cooked (1/2 cup)                1
Spinach, cooked (1/2 cup)                         1

(*) vitamin E added by manufacturer.

source: U.S.D.A. Nutrient Data Laboratory and companies.