Vitamin and mineral supplements for cancer prevention: issues and evidence

Trials of nutritional supplements for cancer prevention must overcome a variety of challenges not shared in the usual paradigm of pharmaceutical agents for prevention of cardiovascular disease. Unlike for cardiovascular disease, for cancer we typically do not have well-established causal risk factors as targets for intervention. Also, for most likely cancer interventions, the expected time to achieve an effect is much longer, more variable, and far less well understood than for cardiovascular disease, and the progression of pathophysiology is much harder-or impossible-to follow, in contrast with imaging for progression of atherosclerosis in cardiovascular disease. Also, cancers at various sites have a wide range of etiologies. The optimal age for intervention, best dose, and duration needed to test nutritional agents for cancer prevention are largely unknown, making null findings hard to interpret. Unlike with drugs, baseline nutritional status can be critical. Moreover, because the nutritional agents are often readily available, adherence in control groups in trials can be impaired. Several gene-nutrient and nutrient-nutrient interactions have been identified that could affect trial results. Some studies suggest that particular nutrients may be effective only in subgroups defined by genotypes or by nutritional status of another nutrient. All these challenges must be considered in planning informative trials. Long-term prospective cohort studies, especially with repeated measures and high follow-up, can provide useful data for planning trials as well as the basis for rational recommendations while awaiting trial results or in settings where trials may be infeasible.