Vitamin D: the more we know, the less we know.

Abstract

Over the last 20 years there have been numerous studies, including NHANES III (the National Health and Nutrition Examination Survey III), the Women's Health Study, and the Nurses' Health Study, showing an association between decreased 25-hydroxyvitamin D [25(OH)D]6 concentrations in blood and the risks of cardiovascular disease, stroke, cancer, fractures, and mortality (see the Supplemental Reading List that accompanies the online version of this Q&A at http://www.clinchem.org/content/vol61/issue3). Approximately 10 years ago, these studies led to recommendations from multiple professional societies that the definition of 25(OH)D deficiency be changed from <20 ng/mL (50 nmol/L) to <30 ng/mL (75 nmol/L). In the US, we and other institutions saw the volume of 25(OH)D testing increase 5–6-fold between 2004 and 2007. Furthermore, the use of <30 ng/mL (75 nmol/L) to define 25(OH)D deficiency results in almost half of the tested population in a large Midwestern US hospital, such as ours, as being vitamin D deficient. In late 2010, the Institute of Medicine (IOM) issued a report that vitamin D supplementation was unlikely to be beneficial for any condition other than bone health and that blood concentrations of 20 ng/mL (50 nmol/L) or greater were sufficient for maintaining bone health. Since then, several metaanalyses have failed to show that low 25(OH)D concentrations are associated with risk for any of the above-mentioned nonskeletal chronic conditions, with the possible exception of fractures. Complicating the association of 25(OH)D blood concentrations with risk has been the poor agreement among 25(OH)D immunoassays (e.g., differences in recognition of 25(OH)D2 and 25(OH)D3, the 2 forms of commercial supplements of the vitamin), for which there are ongoing efforts to standardize 25(OH)D assays. Further complicating what we know and don't know is the recent discovery of genetic polymorphisms in vitamin D binding proteins (VDBPs) that segregate well between blacks and …