The science surrounding vitamin D presents both challenges and opportunities. Although many uncertainties are associated with the understandings concerning vitamin D, including its physiological function, the effects of excessive intake, and its role in health, it is at the same time a major interest in the research and health communities. The approach to evaluating and interpreting the available evidence about vitamin D should be founded on the quality of the data and on the conclusions that take into account the totality of the evidence. In addition, these activities can be used to identify critical data gaps and to help structure future research. The Office of Dietary Supplements (ODS) at the National Institutes of Health has as part of its mission the goal of supporting research and dialogues for topics with uncertain data, including vitamin D. This review considers vitamin D in the context of systematically addressing the uncertainty and in identifying research needs through the filter of the work of ODS. The focus includes the role of systematic reviews, activities that encompass considerations of the totality of the evidence, and collaborative activities to clarify unknowns or to fix methodological problems, as well as a case study using the relationship between cancer and vitamin D.
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