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after the 2009 analysis by the Agency for Healthcare Research and Quality (Chung et al., 2009), hereafter referred to as AHRQ-Tufts, the committee concluded:

  • A dose–response relationship can be simulated based on serum 25OHD measures. That is, serum 25OHD levels can reflect intake, and there are studies that relate bone health outcomes to serum 25OHD levels, as described in Chapter 4.

  • Newer data provide the ability to link vitamin D intakes to the change in serum 25OHD level under conditions of minimal sun exposure, thereby reducing the confounding introduced by the effect of sun exposure on serum 25OHD concentrations. These data also provide an approach for estimating dietary reference values related to intakes that will achieve targeted serum 25OHD concentrations, albeit without regard to the contributions from sun exposure.

Generally, association studies that use a biomarker of exposure in relation to health outcomes can present challenges when establishing reference values. Such measures are not necessarily valid or reliable markers, and they can be subject to considerable confounding by a host of variables. In the case of vitamin D, there are certain factors that allow more confidence in using this measure in the estimation of reference values. Specific deficiencies of vitamin D lead to recognized, measurable deficiency states with adverse effects on the indicator of interest, in this case bone health as evidenced by rickets and osteomalacia. The next consideration is whether the biomarker is an accurate reflection of intake. In the case of serum 25OHD concentrations, despite the lack of clarity about the impact of a number of variables on serum 25OHD concentrations, the measure can be reasonably associated with total intake when sunlight exposure is minimal.

On this basis, serum 25OHD concentrations were used to simulate a dose–response relationship for bone health. Next, the available data—notably those obtained under conditions of limited sun exposure—were integrated in order to estimate a total intake that would result in the desired serum 25OHD relative to measures of bone health. This step-wise process for simulating a dose–response relationship for vitamin D considered, first, the relevance to this study of the confounding introduced by 25OHD assay methodologies and related measurement problems, including “assay drift.” Next, the data from three bodies of evidence described in Chapter 3—the relationship between calcium absorption and serum 25OHD levels; serum 25OHD levels and bone health in children; and serum 25OHD levels and bone health in older adults—were summarized and used to specify a dose–response curve for serum 25OHD. Interestingly, concordance of



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