They were some of the most promising medicines of the 1990s — wonder pills that appeared to fight cancer, heart disease, stroke and other ailments.

Laboratory tests and initial studies in people suggested that lowly vitamins could play a crucial role in preventing some of the most intractable illnesses, especially in an aging population. The National Institutes of Health gave them the same treatment as top-notch pharmaceutical drugs, investing hundreds of millions of dollars in elaborate clinical trials designed to quantify their disease-fighting abilities.

Now the results from those trials are rolling in, and nearly all of them fail to show any benefit from taking vitamins and minerals.

This month, two long-term trials involving more than 50,000 participants offered fresh evidence that vitamin C, vitamin E and selenium supplements don’t reduce the risk of prostate, colorectal, lung, bladder or pancreatic cancer. Other recent studies have found that over-the-counter vitamins and minerals offered no help in fighting other cancers, stroke and cardiovascular disease.

Research has even suggested that, in some circumstances, vitamin and mineral supplements can be unsafe.

No vitamin pills needed?

Some physicians now advise their patients not to bother with taking the pills and to rely instead on a healthy diet to provide needed vitamins and minerals.

“These things are ineffective, and in high doses they can cause harm,” said Dr. Edgar R. Miller, a professor of medicine and epidemiology at Johns Hopkins University School of Medicine in Baltimore. “People are unhappy with their diets, they’re stressed out, and they think it will help. It’s just wishful thinking.”

Yet faith in vitamins runs deep. The Council for Responsible Nutrition, a Washington, D.C.-based trade group, estimates that 64 percent of American adults take vitamin and mineral supplements. Despite the steady drumbeat of reports questioning their efficacy, sales have risen consistently from $5 billion in 1995 to $10 billion this year, according to Nutrition Business Journal.

Scientists remain convinced that vitamins are essential to health. But they have puzzled over how their obvious benefits could be so elusive in randomized controlled trials, the gold standard of medical research.

“You really do need vitamin E. You really do need vitamin C. You really do need selenium,” said Jeffrey Blumberg, director of the U.S. Department of Agriculture’s Antioxidants Research Laboratory at Tufts University in Boston. “Without them, you die.”

Problems with studies

Blumberg and others now believe that a combination of factors — including the versions of vitamins that were tested and the populations they were tested in — probably doomed the studies from the start.

“In retrospect, maybe the expectations were a little bit unrealistic,” said Blumberg, whose research has been funded in part by supplement makers.

Researchers have identified several reasons why vitamins don’t lend themselves to randomized controlled trials. Chief among them is that there is no true placebo group when it comes to vitamins and minerals because everyone gets some in their diet.

“For drugs, someone either has (the impotence drug) Cialis in their system or he doesn’t have Cialis,” said Paul Coates, director of the National Institutes of Health Office of Dietary Supplements in Bethesda, Md. With vitamins, on the other hand, “there’s a baseline exposure that needs to be taken into account. It makes the challenge of seeing an improvement more difficult.”

A vitamin’s benefit may become apparent only if people aren’t getting enough of it already.

The observational studies that originally linked vitamins to better health may have been biased because people who take supplements are healthier overall than people who don’t.

The data collected by these massive studies isn’t useless. Researchers said they could spend years slicing and dicing it to see if they can tease out a positive effect in a subgroup.