In search of the magic nutraceutical: problems with current approaches.

Over the last few decades, substrates with immune-modulating properties have been identified in all groups of micro- and macronutrients. Numerous experimental studies have focused on evaluating these substances, either alone or in combination. After hundreds of experiments, no clear, consistent signal exists that any of these agents result in significant treatment benefits in critically ill patients. The current approach to establishing the efficacy of nutritional interventions suffers from several limitations. First, the majority of studies focus on surrogate or substitute end points rather than clinically important end points. Second, the majority of clinical studies are small, and as such are underpowered to detect a significant treatment effect on clinically important end points. Third, the methodological quality of individual randomized trials varies. Methodological limitations, prevalent in nutrition studies, limit the strength of clinical inference that can be made from study results. High quality studies have been shown to differ significantly from low quality studies in their estimation of treatment effect. Fourth, the generalizability of single-site studies is limited. Finally, studies sponsored solely by industry are considered to be less believable than studies conducted under the auspices of peer-review agencies. Future evaluations must be done in the context of large, multicenter, well-designed, randomized trials focusing on clinically important end points that are sponsored from a variety of sources (including peer-reviewed agencies). Although such trials are costly, they are feasible and are much more likely to be believable and generalizable than the current approach.