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to understand whether local production of calcitriol has an impact on health outcomes. In turn, the relevance of vitamin D nutriture and serum 25OHD for such an effect should be established.

  1. Clarify the extent to which differences exist between vitamin D2and vitamin D3. Physiological responses as well as potential for differences in safety risks for the two forms of the nutrient should be further explored.

Synthesizing Evidence and Research Methodology

  1. Explore enhanced methodologies for data synthesis. Alternative methods for synthesizing evidence from different study types and multiple parameters that consider uncertainties (including measurement error) include teleoanalysis, confidence profile predictive meta-analysis, and generalized multi-parameter evidence synthesis. In the case of calcium and vitamin D, such approaches should facilitate quantitative estimates of effect size and dose–response relationships as needed for DRI development.

  2. Identify approaches to weight better potential health outcomes. In order to ensure the most objective and comprehensive systematic evidence reviews in the future, approaches to better weight potential health outcomes are needed.


The committee encountered major challenges in determining the dose–response relationships for calcium and vitamin D. Sun exposure introduced further uncertainties regarding vitamin D.

Research Related to Dose–Response Relationships

  1. Conduct studies to identify specific health outcomes in relation to graded and fully measured intakes of calcium and vitamin D. Too few studies are specifically designed to study the effects of graded doses of calcium or vitamin D on health outcomes, both overall and as part of the same study using the same subjects and outcome measures. Further, many studies in the calcium and vitamin D area are confounded by the failure to specify or measure and thereby take into account “background” intakes of the nutrient being studied when dose–response is being explored.

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