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Why we know so little about effects of vitamin D supplements

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The March issue of The Scientist has a great article outlining the considerable barriers facing researchers who are seeking proof that vitamin D supplements can help prevent a slew of diseases, including cancer, diabetes, stroke and multiple sclerosis.

The article also explains why, despite all the positive headlines about vitamin D, we really don’t have any solid evidence yet that taking vitamin D in supplemental form will improve our health. Almost all we have so far are observational studies, which can show only a correlation between two things, not a causation. And correlations are often misleading. (The sun comes up each morning while I’m writing this Second Opinion column, but that doesn’t mean my writing of the column causes the sun to rise.)

What we need are large-scale clinical trials — ones in which many thousands of participants are randomly assigned to take either a vitamin D supplement or a “sugar pill” for many years while their health is periodically assessed and recorded. But those studies are notoriously difficult and expensive to do.

Yet, as reporter Amy Maxmen points out in The Scientist article, the public — and many doctors — aren’t waiting for rigorous clinical trials:

Spurred by headlines about its potential benefits, US consumer sales of vitamin D supplements rocketed from $50 million in 2005 to $550 million in 2010, according to estimates from the Nutrition Business Journal. Enthusiasm for the vitamin echoes among doctors and natural-food advocates, who are pushing for doses higher than the 400 to 600 International Units (IU) that the government currently recommends for maintaining healthy bones.

However, [epidemiologist JoAnn] Manson [at Harvard Medical School in Boston], a refined woman of measured words, is acutely aware of the disappointment that has trailed the hyping of vitamins over the decades. Vitamin E, a fat-soluble antioxidant, gained a reputation for fighting cancer in the 1990s, when observational studies found that people who took supplements had lower rates of the disease. But the buzz died out in 2008 when a 35,000-person clinical trial on vitamin E and selenium was terminated prematurely after people taking the supplements showed a slightly higher risk of developing prostate cancer than the control group.

Similarly, in 1996 two large clinical trials dumbfounded fans of beta-carotene, a substance that humans convert into vitamin A after consuming it in fruits and vegetables. One trial found that it raised the risk of lung cancer and heart disease, and the other ended anticlimactically after 12 years with the conclusion that beta-carotene supplements performed no differently than placebo. “You have to look at these previous randomized trials as cautionary tales,” Manson says, “because they show that time and time again, everyone jumped on the bandwagon and then the randomized trials did not have favorable results, and in fact, the risks outweighed the benefits.”

At the same time, however, this is exactly why large-scale trials are necessary, she says. Though they aren’t perfect, such trials are the only way to discover whether vitamin D causes better health, or simply indicates it. “For example, people who are physically active tend to spend more time outdoors walking, hiking, or playing tennis. They get more sun exposure” — and thus more vitamin D — “but the real benefit might be physical activity,” says Manson. “There are so many potential confounders, and this is just one we know about.”

Manson is heading the largest vitamin D intervention trial yet, a 5-year, $22 million study called VITAL (VITamin D and omegA-3triaL). But to keep that study’s costs down, she and her colleagues have had to cut some corners. They are giving the study’s 20,000 participants only 2,000 IUs of vitamin D daily, which critics say will be too low to see any health effects. They are also mailing the randomly assigned pills (the vitamin D and the inert placebos) to the study’s participants, which means the researchers won’t know for sure if the pills were actually taken. Also, because it’s considered medically unethical to ask anyone to go without vitamin D, the volunteers are free to take the supplements on their own. If enough of them do that, it could seriously skew the study’s results.

“A better vitamin D trial might send health-care professionals out to personally deliver pills to each of the [study’s] 20,000 participants,” writes Maxmen. “It might also test various doses of supplements, because no one knows how much is best.”

But that would cost too much.

A half a dozen or so other vitamin D clinical trials are currently under way, reports Maxmen, but each has its own methodological problems. Still, these studies may be the best we get.

While waiting for the results, which will start rolling in over the next few years, consumers may want to keep in mind those government vitamin D recommendations that Maxmen mentioned. After an extensive review of all existing data, the Institute of Medicine (IOM) reported late in 2010 that most Americans under the age of 70 need no more than 600 IUs of vitamin D daily to keep their bones healthy — an amount, the IOM experts added, that seldom requires supplementation.

For, as the IOM report pointed out, most Americans — yes, even those of us living in the northern latitudes of Minnesota — get plenty of vitamin D from our food and from natural sunlight.


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