Vitamins: Benefit of the doubt vs. doubts about benefit
Good news about vitamins is hard to find these days. B vitamins don't prevent heart attacks. Vitamin E doesn't benefit people with Alzheimer's disease. Vitamins A, C, and E — no cancer protection there.
Mixed in with the null findings are a few that suggest large doses of vitamins might cause some real harm. One of the first came in 1994, when a high-profile Finnish study linked beta carotene, a form of vitamin A, to an increased risk of lung cancer in male smokers. Several years later, high intake of retinol — another form of vitamin A — was linked to hip fractures. More recently, folic acid has come under some suspicion. Studies have identified a possible connection between high intake of this B vitamin and increased risk of cancer, particularly colon cancer.
Taking large, "megadoses" of individual vitamins has been a dubious proposition for quite some time (although exactly what constitutes a megadose is ill-defined). There are, though, at least two notable exceptions. First, pregnant women — indeed, all women of childbearing age — should get extra folic acid (400 micrograms daily) to protect against birth defects. Second, there's growing evidence that most Americans — particularly those in the northern two-thirds of the United States — would benefit from getting between 800 international units (IU) and 1,000 IU of vitamin D daily, which is twice as much as the official recommendation.
What is new is that the multivitamin has become a harder call these days. For years, even the most mainstream of doctors have been comfortable recommending them. They're affordable and can be an easy way to fill in the nutritional gaps in our diets. And where we don't have gaps, they supply modest surpluses.
But as the negative findings of studies of vitamins have piled up, there's been some pulling back. In 2009, results from a large study of postmenopausal women were published that showed multivitamin use had little to no effect on cancer and cardiovascular risk.
Vitamins are organic (carbon-containing) compounds that we must ingest in small amounts for our bodies to function properly. Thirteen vitamins have been isolated and identified: eight different B vitamins and vitamins A, C, D, E, and K.
Historically, the problem with vitamins was that people didn't get enough of them. But as the food supply became more reliable and diets improved, the focus shifted from absence to addition and whether consuming vitamins in abundance might fend off disease and perhaps even prolong life.
...and the bust
But amid all the vitamin mania, researchers were quietly running vitamins through the gauntlet of randomized trials. Hundreds, if not thousands, of results have now been published. Not all the results are negative by any means, but there's a persuasive tilt in that direction.
Vitamin C was first to travel from vaunted to vanquished. Studies showed the vitamin did not prevent colds and was not useful in treating colon cancer, as was hoped. In late 2008, Harvard researchers added another finding to the list that vitamin C does little, if anything, to prevent heart attacks and strokes.
Vitamin E looked promising because of its strong antioxidant effects — and doctors believed it, too. But randomized trial results haven't been kind to E, either. Alzheimer's disease, heart disease, cancer — reports in 2005 made the vitamin out as ineffectual against all three.
And it's been a bumpy ride for the B vitamins, too. The hope was that a trio of them — B6, B12, and folic acid — might be an easy way to rake back heart disease risk because they lower levels of homocysteine, an amino acid in the blood. In randomized trials, they've reduced homocysteine levels, but that reduction hasn't translated into lower heart disease risk.
Limits of randomized trials
Much of this bad news for vitamins has come in the form of negative results from randomized trials, which in medical circles is damning evidence indeed. The randomized trial is considered the true test in medicine — the final arbiter of whether or not something works.
But when it comes to evaluating how well vitamins — and other preventive measures — protect us against chronic diseases like cancer and heart disease, the randomized trial may have some blind spots. For one thing, it may take decades for conditions like cancer or dementia to develop. So even if a trial lasts many years, that might not be long enough to pick up on the effect of an intervention, particularly if it's subtle. There's also a question about applying narrow randomized trial results to everyone.
Results from randomized trials can also be misleading if the findings for a subset of people differ from the overall ones.
That elusive bottom line
Despite all the back-and-forth, there are a couple of areas of agreement. Added vitamins have lost their sheen, and there are more doubts than ever about taking them in pill form. Large doses of single vitamins aren't a good idea: the benefit is doubtful, and some can cause harm. The notable exceptions are vitamin D, and folic acid for young women.
And what about multivitamins? The doses they contain aren't likely to pose any risk, but the leap of faith that we're getting benefit from them has definitely gotten longer. On the other hand, it's a reasonable choice to take a multivitamin — or not to, if you have a well-rounded diet.
April 2009 update