Tuesday, October 23, 2012

Curbing the Enthusiasm on Daily Multivitamins

Carl Wiens
Can you reduce your risk of cancer by taking a multivitamin every day?
Last week, Boston researchers announced that one of the largest long-term clinical trials of multivitamins in the United States — encompassing 14,000 male physicians 50 and older, and lasting over a decade — found that taking a common combination of essential vitamins and minerals every day decreased the incidence of cancer by 8 percent, compared with a placebo pill.
Men who had already had cancer earlier in life were most likely to benefit, the study found. Cancer deaths also were lower among those who took vitamins, though that may have been a chance finding. Curiously, the vitamin regimen did not reduce the rate of prostate cancer, the most common cancer affecting men.
The researchers also looked for side effects and found that daily vitamins caused only minor problems, like occasional skin rashes.
Even though an 8 percent reduction in the overall cancer rate is fairly modest, Dr. Demetrius Albanes, senior investigator at the National Cancer Institute, said the potential public health implications were vast. “If you think of the hundreds of thousands of new cases of cancer every year, 8 percent can add up quite a bit,” he said.
Yet no one is rushing out to urge more Americans to take multivitamins. Although half the population already takes some kind of supplement, previous studies have yielded decidedly mixed results. Some trials of high doses of nutrients believed to be cancer-fighters were shut down prematurely when they backfired, driving up cancer rates instead of reducing them.
Current federal dietary guidelines and American Cancer Society recommendations encourage people to eat a balanced diet rich in fruits and vegetables. Until now, the consensus has been that there is insufficient scientific evidence to justify taking a multivitamin to prevent cancer or other chronic diseases.
Though a large trial in Linxian, China, found decreases in stomach cancer in people randomly assigned to supplements including vitamin E, selenium and beta carotene, that population suffered from chronic nutritional deficiencies, and stomach cancer was more common than in the United States.
A review by the National Institutes of Health in 2006 concluded that evidence was “insufficient to prove the presence or absence of benefits from use of multivitamin and mineral supplements.” More recently, the Institute of Medicine cautioned people on vitamin D and calcium supplements, saying that most healthy adults do not need them and that high doses of calcium have been linked to kidney stones and heart disease and that high doses of vitamin D may also be harmful.
Dr. J. Michael Gaziano, a cardiologist at Brigham and Women’s Hospital and the V.A. Boston Healthcare System who is the lead author of the new multivitamin study, said the main reason to take a multivitamin was, and continues to be, to prevent nutritional deficiencies. He was reluctant to speculate about how a multivitamin might curb cancer. One of the dominant hypotheses, he noted, is that certain vitamins are antioxidants that protect aging cells against oxidative damage caused by free radicals, harmful molecules resulting from metabolic processes within cells.
The physicians study was a type of clinical trial considered highly reliable at determining cause and effect: participants were randomly assigned to take either a multivitamin or a placebo. But they were not representative of the population at large. The doctors were a fairly homogeneous, well-educated group, less racially and ethnically diverse than the population as a whole, with far fewer smokers. And, there were no women.
“The results are promising, but we want to make sure the effects would be similar and certainly not harmful across different populations,” said Marji McCullough, a nutritional epidemiologist with the American Cancer Society. “It’s worth trying to replicate these findings to see if they’re generalizable to women, smokers and others.”
Dr. McCullough also noted that there are different multivitamin combinations and the trial results would apply only to the specific formulation used in the study. Pfizer donated the multivitamins, called Centrum Silver, but the company has tinkered with the formula since the trial began — reducing the amount of vitamin A, for example, and adding the nutrients lutein and lycopene.
Generally speaking, people who take vitamins are a relatively healthy bunch to begin with, experts say. They tend to eat a varied and healthful diet, watch their weight and be physically active. It’s not always clear that the benefits they attribute to vitamins actually result from the pills.
“There’s a mystique about vitamins, that vitamins are some type of magical ingredient,” said David G. Schardt, senior nutritionist for the Center for Science in the Public Interest, an advocacy group in Washington. “There is a kernel of truth in that, because vitamins are essential to life. But that people will live longer or healthier lives if they take vitamins or eat foods fortified with vitamins — that’s difficult to prove.”
This year the center pressed Pfizer to change Centrum labels that said the multivitamins supported “breast health” and “colon health.” Such claims have to be approved in advance by the Food and Drug Administration, and even though the labels did not say explicitly that the supplements prevent cancer, the center alleged that was the implied message.
Experts are particularly concerned about letting the enthusiasm get ahead of the scientific evidence, because some vitamin trials have led to frighteningly paradoxical results. In two separate studies, smokers who were given supplements of high doses of beta carotene unexpectedly developed more lung cancers than those on placebos. Beta carotene was believed to protect against cancer, but it appears that in smokers’ lungs, the high doses actually caused DNA damage instead of protecting against it, Dr. McCullough said.
Another large study, involving 35,000 men who were given vitamin E and selenium in the hopes of reducing prostate cancers, also had disappointing results.
While deficiencies of certain nutrients can be harmful, an excess in some cases may also be bad, said Dr. Joel B. Mason, professor of medicine and nutrition at Tufts University. Like some medications, certain nutrients and vitamins may need to be delivered within a specific optimal range to confer benefit, he said, a concept he and others have termed a “Goldilocks phenomenon.”
“I think there is pretty compelling evidence that habitual underconsumption of folate does lead to an increase in colon cancer, and perhaps a few other types of cancer as well,” Dr. Mason said. “Folate is an essential factor in the synthesis and repair of DNA.”
But giving a well-nourished population folate supplements does not seem to decrease the risk further, Dr. Mason said, and some studies have indicated that “in some people who take extraordinarily large amounts of folate, there may be a paradoxical increase in colorectal cancer.”
One of the important observations of the new study is that a daily multivitamin appears to be fairly safe. That may also help shape the direction of future research, said Dr. Albanes, the senior investigator at the National Cancer Institute.
“The idea that ‘if a little is good, more is better’ led to trials with higher doses that didn’t necessarily come to fruition,” Dr. Albanes said. “This points us in the direction of the kinds of dosages that should be considered for prevention. It’s food for thought.”

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