Antioxidants nixed again in healthy heart quest

Washington -- Theoretically, antioxidant vitamins should provide heart-healthy benefits, but the evidence from clinical trials is clearly coming down on the negative -- as in forget-about-it -- side of the equation, particularly for women.

The latest in a string of studies on vitamins C, E and beta carotene found no reduction in cardiovascular events among a group of about 8,000 women at high risk for heart disease who consumed various combinations of the vitamins over nine years.

The study was in the Aug. 13/27 Archives of Internal Medicine.

The researchers' conclusion is not surprising, given similar findings that have emerged during the past several years. But it is disappointing, since popping a handful of vitamins undoubtedly would be easier than sticking to an appropriate diet and getting sufficient exercise.

Clearly, healthier hearts and blood vessels are a prevention imperative. Heart attacks and strokes cause more deaths in Americans -- among both genders and all racial and ethnic groups -- than do any other diseases, according to the Centers for Disease Control and Prevention.

Although the trial was conducted with women, there is no evidence that men and women differ in their responses to antioxidants, said Dr. Pamela Ouyang, professor of medicine at Johns Hopkins University in Baltimore. Dr. Ouyang participated in an earlier trial on antioxidants.

The reason so many researchers have poured so much time and energy, not to mention resources, into the quest for what could have been a magic-bullet cure for heart disease is the evidence that had accumulated from basic science and animal studies. These early indicators suggested that vitamins could prevent harmful oxidation processes in the blood vessels.

Although most agree that it was a great initial thought, data did not follow to back it up. "I think there is clearly no evidence to support the idea," said Paul D. Thompson, MD, director of cardiology at Hartford Hospital in Hartford, Conn.

And it is not the first time this pattern has emerged. "We live in a time where many similar circumstances have occurred where we have had reason to believe that something might actually be beneficial and it proved not to be. And sometimes it proved to be harmful instead," noted David Herrington, MD, MPH, director of the Translational Science Institute at Wake Forest University in Winston-Salem, N.C.

Hormone therapy's supposed cardiovascular benefits and the heart risks discovered, belatedly, from the pain reliever Vioxx are just two recent cases where research findings resulted in reversals of fortune for what had been considered useful medications, he noted.

"The landscape is littered with examples that proved to have results different from what was anticipated once they were put to the test of a formal clinical trial," he said.

The findings also point up the complexities of the human body and how various systems interact with nutrients, said Alice Lichtenstein, DSc, professor of nutrition, science and policy at Tufts University in Boston, Mass. "There are multiple systems which can alter almost any of the individual reactions that we can measure outside the body."

Study author Nancy Cook, ScD, associate professor of preventive medicine at Harvard Medical School, isn't ready to give up on all antioxidants, although her study seems to point in a negative direction. "There is a possibility that combinations of nutrients might have an effect. So it's not clear that there is no remaining effect of any antioxidants."

On the bright side

Her study actually found there was some evidence of fewer strokes as a result of taking vitamins C and E. "While that is intriguing, it could be a false-positive result," Dr. Cook said, leaving the door open for other researchers to duplicate the finding.

But at this point, many different studies have failed to find the overall benefit of antioxidants, Dr. Cook acknowledged. "It's possible there may be some benefit to some groups, but it doesn't seem it should be advocated for the general population."

Despite the findings, however, patients still are consuming vast numbers of these vitamins, and there may be no way to persuade them to stop.

"I think anybody who practices medicine has a lot of patients who will take anything except what you prescribe to them," Dr. Thompson said.

David Waters, MD, professor emeritus in the Dept. of Medicine at the University of California San Francisco, received a barrage of e-mails after he published findings in 2002 showing that vitamins E and C had no cardiovascular benefit.

He was asked whether he used the natural or the artificial form of vitamin E and when he responded that it was the artificial kind, his correspondents said, "No wonder it didn't work. If it was natural vitamin E, it would have worked." But both types are basically the same, he added.

"There is a community of people out there who, if you tell them it's a vitamin, they think it is good for them. They think it is healthy. If you tell them it is a compound made by a pharmaceutical company, they think pharmaceutical companies are evil, so it is probably toxic. It's not rational sometimes," he said.

Meanwhile, Dr. Waters has moved away from research on vitamins and is now involved in clinical trials of drugs that affect cholesterol or atherosclerosis. "It's the same idea, but not with vitamins," he said.

Plus, he's moved beyond statins to conduct research on drugs that raise HDL levels and are anti-inflammatory. "There are lots of other exciting things to do, and vitamins are sort of like Hula Hoops or the Bee Gees," he added.

Although the halt last December of a late stage trial on torcetrapib, a drug to raise HDL levels, was a "huge disappointment," Dr. Waters said, he remains optimistic that in five to 10 years there actually will be drugs that will decrease the number of coronary events in patients.