title: Key questions in vitamin D research.
abstract: Despite interest and expanding research on non-bone health outcomes, the evidence remains inconclusive concerning the causal role of vitamin D in the non-bone health outcomes. To improve our understanding of its role, research needs to address five key areas related to vitamin D: 1) its physiology and molecular pathways. 2) its relationship to health outcomes. 3) its exposure-response relationships, 4) its interactions with genotype and other nutrients and 5) its adverse effects. Its metabolism needs to be elucidated including extra-renal activation and catabolism, distribution and mobilization from body pools, kinetics of this distribution, and their regulation during pregnancy and lactation. Rigorous, well-designed randomized clinical trials need to evaluate the causal role of vitamin D in a diverse array of non-bone health and chronic disease outcomes across the life cycle and reproductive states. Critically needed is the determination of the exposure-response, inflection and threshold of serum 25(OH)D concentrations relative to functional and health outcomes. The dose-response relationships of standardized measures of serum 25(OH)D need to be understood in response to low and high doses of total vitamin D with careful consideration of confounding factors including catabolic rates. How do relevant genetic polymorphisms, dietary calcium and phosphate and potentially dietary cholesterol interact with vitamin D exposure on its bioavailability, transport, distribution in body pools, metabolism and action as well as on bone and non-bone health outcomes? The nature and mechanisms of U-shaped risk relationships with adverse health outcomes at higher exposure to vitamin D needs elucidated across the life cycle and reproductive stages.
authors.affiliation: Cornell University, Ithaca, NY, USA. pmb22@cornell.edu
authors.forename: Patsy M
authors.initials: PM
authors.lastname: Brannon
mesh_terms: D004305:Dose-Response Relationship, Drug; D005838:Genotype; D006801:Humans; D014807:Vitamin D / Q000009:adverse effects / Q000031:analogs & derivatives / Q000097:blood / Q000502:physiology*; D014809:Vitamin D-Binding Protein / Q000097:blood
chemical_list: D014809:Vitamin D-Binding Protein; D014807:Vitamin D; C104450:25-hydroxyvitamin D