Clinical Practice

This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors' clinical recommendations. A healthy 54-year-old, nonsmoking, omnivo-rous woman presenting for a routine examination asks about vitamin supplements. She expresses confusion about conflicting reports and recommendations. She currently uses no supplements. Medical teaching has been that, in generally healthy persons, nutritional needs can be readily met by diet alone. However, recent evidence shows that the use of folic acid supplements in early pregnancy can dramatically reduce the incidence of neural-tube defects; thus, at least in some circumstances, vitamin intake can be suboptimal without there being any clinical evidence of deficiency. Public interest in vitamin supplements is enormous, with 30 percent of the population of the United States currently using such supplements. 1 Political pressures have led to a highly unregulated industry with limited control by the Food and Drug Administration over marketing and quality. Ideally, vitamin supplements would be evaluated in randomized prevention trials with measurable clinical end points. However, such trials are complicated , and the results could be misleading. First, everyone has some level of consumption of vitamins, so the effect of a supplement depends on the amount of a given vitamin that is already being consumed. Because trial participants often have good diets, the results of a study finding no effect of a vitamin supplement might not apply to those with poorer diets. Moreover, a trial may be too short for an effect to be detected, particularly in the case of the incidence of cancer. In addition, to enhance their statistical power , many studies focus on persons at high risk for a disease or those with existing disease. If diet is not responsible for the elevated risk, such a focus could obscure a benefit that might be observable in a population with average risk. In general, clearly positive results would be compelling, but negative results would be difficult to interpret. One approach is to discourage the use of vitamin supplements unless benefits are proved in random-ized trials with measurable clinical outcomes. An alternative is to use all the available evidence to weigh the likelihood of a benefit against the likelihood of harm, while also considering the costs. Evidence should include the results of animal studies, randomized trials examining intermediate biologic markers, …