Future approaches for DRI development are likely to be increasingly more sophisticated in their inclusion of an array of physiological, environmental, and genomic characteristics. The interplay of these factors in determining the prevalence of various phenotypes will need to be recognized, and the interpretation of the special nutrient needs imposed by this interplay will require an expanded DRI process. This increased sophistication will impose important challenges to further address knowledge gaps, mechanistic complexity, and the present inadequate understanding of interactions among diverse environmental conditions and individual behavioral choices.

Finally, an improved understanding of genomic influences on health will cause us to rethink the use of DRIs in designing strategies to promote individual and population health.

An audience member commented that genomic variability and the presence of polymorphisms will undoubtedly play an increased role in DRI development. However, after describing the example of methylenetetrahydrofolate reductase polymorphism, he suggested that the changes involved may not be dramatic. Dr. Garza added that we often forget that these polymorphisms were positively selected. At some point in our evolution, they must have played some beneficial role. In some context, they may increase risk, whereas in other contexts, they may be protective.

Another participant addressed the issue of environmental influences, noting that Dr. Garza had mentioned infectious diseases as pertinent to nutrient reference values for persons in developing countries. Given that inflammation is shown to play a role in the pathogenesis of chronic diseases and may be relevant to the aging North American population, the participant questioned whether inflammation should be added to the list as either a physiological or environmental factor to be considered. Dr. Garza responded that aging is germane, and the physiological adjustments and metabolic abnormalities that accompany aging, are relevant to the derivation of future DRIs.