majority of case-control and cohort studies are not simple repeats of previous undertaking and thus vary enormously in experimental design, tested populations, and outcome measures; all of this can surely influence overall interpretations. Unfortunately, conclusions based on a meta-analysis may even depend on the method the authors used to select trials for inclusion in the analysis. Thus, summaries of evidence which do not consider the biological response, plausibility and consequences are doomed to create more confusion than they resolve. What is increasingly clear is that inadequate long-term intervention studies exist for making definitive conclusions about who will benefit and who might be placed at risk by dietary change. Indisputably, well-controlled long-term intervention studies which incorporate the newest technologies hold the greatest promise for unraveling the complex interplay between diet and health. Future clinical studies must incorporate genomics in the study design, and not just use it as an analytic approach to confounders to data interpretation. Considerable preclinical evidence linking diet to health outcomes centers on the response to a single bioactive component as a modulator of a key cellular process or series of critical processes [7, 8]. Both in vitro and in vivo studies suggest that multiple targets are likely responsible for the phenotypic response to foods and/or dietary supplements [8, 9]. These targets may be involved in cell division, inflammation, apoptosis, compound bioactivation or a host of other biological processes which influence the phenotype. Focusing on a process which can be modified by one or more bioactive food components will help with a systematic approach to understanding the role of diet in health promotion. However, in some cases, research suggests that whole foods may offer advantages over isolated components, possibly indicating that multiple food components or multiple targets are needed to bring about a desired effect. Nutrient-nutrient, as well as nutrient-drug interactions can be significant determinants of the overall phenotypic response. For example, the ability of n–3 fatty acids to increase the sensitivity to anthracyclines is dependent on vitamin E intake [10] or the benefits of calcium are generally dependent on the intake of vitamin D [11]. While not as frequently examined, negative interactions among food components or nutrient-drug interactions are also possible and such lines of investigation deserve added attention to assist with the identification of potentially vulnerable individuals. Since the quantity of exposure can markedly influence the outcome, it is imperative that nutrition studies use physiologically relevant concentrations and consider the totality of the diet as a factor influencing the overall response [7, 8]. Sadly, multiple exposures in humans are hampered by the availability of definitive biomarkers that reflect a long-term health outcome. Finally, it is worth noting that studies which examine the impact of dietary change through more than one phase of life are exceedingly rare, yet are desperately needed if
Nutrition and Genomics
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