Alphabet overload: Which dietary supplements are effective?

From vitamin A to zinc, supplements line supermarket and drug store shelves in a mind-numbing proliferation of strengths and configurations. Health claims on labels stay narrowly within legal boundaries -- catching the eye and raising the hopes of unwary consumers.

At least a third of the population takes a vitamin and mineral supplement every day, according to a recent federal survey. And sales in the United States reached $6.6 billion in 2003, a 7% growth over the year before, with about half spent on multivitamins and B vitamins as well as C and E. But which of these, if any, should be taken is a puzzle for patients and for their physicians.

Adding to the problem is that some patients aren't forthcoming about the supplements they are taking, unaware that harmful interactions with some medications and some conditions can occur.

A recent clinical trial, for instance, linked beta-carotene supplements with higher rates of lung cancer in heavy smokers. Another trial found that vitamin E can cause increased bleeding, especially among people already taking anticlotting medication.

Then there's the question of proper dosing, because large amounts can sometimes be counterproductive.

It's not difficult to get too much vitamin A, said Meir Stampfer, MD, DrPH, chair of the Harvard School of Public Health's epidemiology department. "Between supplements, fortified breakfast cereals and milk, it's easy to get up to 10,000 or more international units per day, and that's a level where you start to see clinical harm in terms of increased susceptibility to fractures and other adverse health effects."

Also because of food fortification, it has become fairly easy to exceed the recommended 2,500 mg a day upper limit for calcium.

Meanwhile, the landscape is further complicated by the fact that related research often has contradictory findings. Imagine the confusion of patients with arthritis who read headlines one week that too much vitamin C might be bad for their condition and the next that a diet rich in vitamin C could cut arthritis risk.

It's perplexing on several fronts, Dr. Stampfer said. "On the most basic level, the knowledge base truly isn't there for many supplements." And many patients don't understand that there is little regulatory oversight of this burgeoning industry.

Under the Dietary Supplement Health and Education Act, which became law in 1994, manufacturers are responsible for ensuring the safety of their products. Medicines must be proven safe and effective to the satisfaction of the Food and Drug Administration, but dietary supplements, which include herbal products as well as vitamins, do not.

"It's astonishing that a marketer is not required to show any evidence of efficacy at all," Dr. Stampfer noted.

Healthy living

It's a given that vitamins are essential for life and that inadequate intake is a risk factor for chronic disease. If everyone ate their five to nine daily servings of fruits and vegetables as recommended by the Dept. of Health and Human Services, all might be well. But few do.

"By and large, Americans are not eating very healthily," said Jeffrey Blumberg, PhD, chief of the antioxidants research lab at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University in Boston.

To make up for dietary deficiencies, physicians should recommend that all their patients take a daily multivitamin/multimineral pill, Dr. Blumberg said. A multivitamin can act as insurance by filling gaps left by inadequate diets. This recommendation was among those advanced last fall by an expert panel on nutrition chaired by Dr. Blumberg.

To fine-tune that suggestion, he advises that for young women, the multivitamin contains at least 400 micrograms of folic acid. A randomized clinical trial conducted in Britain concluded that folic acid reduced the risk of neural tube defects in newborns by 70% among high-risk women.

The FDA now requires that food be fortified with folic acid, but some fear that adequate amounts might not be consumed by the group most in need -- women of childbearing age. "I can tell you that maybe 30% of women of childbearing age are taking a multivitamin [with folic acid], and a 30% compliance rate is not what I would call great," Dr. Blumberg said.

Taking a patient-by-patient approach can work with supplements other than folic acid. For example, vitamin B-12 supplements are a prudent recommendation for older patients who lose the ability to gain this nutrient from their diets. "It's not that they are exhibiting clinical symptoms, but they aren't doing as well as they could," Dr. Stampfer said.

And calcium and vitamin D are still needed for bone health despite the growing popularity of drugs such as the bisphosphonates and calcitonins. Dr. Blumberg cautions that the drugs need to build on a strong substrate of bone, which is where vitamin D and calcium enter the picture.

But whether men should be taking calcium supplements is a point of contention. While many physicians recommend supplements for men and women alike, Dr. Stampfer doesn't advise supplemental calcium for men of any age because a number of studies show that a higher calcium intake is associated with an increased risk for prostate cancer. "The studies for fracture risk for men aren't as convincing for calcium alone," he said. "But for women, I don't see any downside."

Adequate consumption of the two nutrients is especially important for teenage girls, for whom supplements might be indicated, Dr. Blumberg said. "I would be happy to engage in a debate about it, but my opponent would have to convince me that you can readily get adolescents to consume enough milk and cheese and fish oils."

While strong cases can be made for taking a multivitamin and, at least for certain populations, supplements of folic acid, B-12, vitamin D and calcium, beyond those well-researched nutrients, the vitamin picture becomes murky.

The C and E puzzle

The data are mixed for the preventive powers of vitamins C and E, whether alone or in tandem.

"Many of my patients take vitamin C religiously, although I never recommend it," said Mary Pickett, MD, assistant professor of medicine at Oregon Health & Sciences University. Vitamin C's health claims, whether for warding off colds or preventing cancer, have not borne up in clinical trials.

Patients older than 65 are particularly interested in taking vitamin supplements that might help prevent dementia and Alzheimer's disease, said Michael Weiner, MD, MPH, an assistant professor of medicine at Indiana University School of Medicine. "While there have been some observational data consistent with the benefits on memory of vitamin E, the randomized trials aren't there yet."

And the American Heart Assn. recommended in the Aug. 3 issue of Circulation that people get their antioxidants from food, not supplements, to reduce the risk of heart disease. Most physicians, though, would not object to patients taking vitamin E or other vitamins in safe doses. There is still a chance they could help, Dr. Weiner said.

One study showed that high levels of vitamins C, E, beta-carotene and zinc could slow the advance of age-related macular degeneration and cataracts.

Dr. Stampfer takes 400 IUs of vitamin E daily. "The way I look at it is: Let's say there's a 10% chance that it is doing me some good, at that [low] price, I'll take the gamble."

And it's possible that vitamin E plays a beneficial role for certain people.

"When someone says vitamin E might reduce the risk of cancer or heart disease or dementia or cataracts or infectious disease because it increases immune function, I think that might be true, we just don't know for whom it is true," Dr. Blumberg said.

There is also some provocative evidence that taking supplemental folic acid with vitamins B6 and B12 can lower homocysteine levels, which can, in turn, reduce the risk of cardiovascular disease, Dr. Blumberg said. But the evidence is not yet solid enough to promote widespread homocysteine testing. "Clearly people are waiting for more science to come out before it is a standard like cholesterol testing," he said.

A stronger scientific base could definitely help physicians sort through the jumble of A, Bs and C to determine which vitamins are best for which patients.

"It's true that the studies are a little expensive and sometimes don't give exactly good, crisp answers," Dr. Stampfer said. "But we have to keep moving to improve our knowledge."

Dr. Stampfer also would like better regulation. "Not to tie peoples' hands, but just to avoid unscrupulous, misleading claims that take advantage of the complexity and people's desire for health," he said.

The AMA has pushed for stronger FDA oversight of dietary supplements for years.

Although manufacturers are prohibited from making claims that their products can treat or cure a specific disease, "it appears that many vendors of dietary supplements are ignoring the law's prohibition in their promotion," AMA Trustee Ron Davis, MD, told a congressional subcommittee in June.

The House already has passed legislation to require manufacturers to report adverse events from supplements, and the Senate is considering similar legislation. Such reporting is currently voluntary.