Endocrine Abstracts

Research into the role of vitamin D in human health has significantly increased. Best known for its role in calcium and bone metabolism, it is now also acknowledged to play a role in non-calcaemic processes, including muscle and immune function. For many of these, randomised controlled trials are underway and mechanisms are only partly understood. The plasma concentration of 25-Hydroxy-vitamin D (25OHD) is considered the best marker of vitamin D status. The free fraction of 25OHD has been proposed as an additional or better measure of tissue availability. Free 25OHD is calculated from total 25OHD, vitamin D binding protein (DBP) and albumin concentrations or directly measured by ELISA. The free hormone theory states that only the free fraction can enter cells. This may however not fully apply to 25OHD since several organs express a megalin-mediated internalisation mechanism for DBP bound metabolites. In healthy people, plasma total and free 25OHD are highly correlated. Specific physiological and pathological conditions are associated with alterations of plasma DBP and the relationship between total and free 25OHD, such as renal disease and pregnancy. The impact of these variations on tissue 25OHD availability is unclear. Compared to total 25OHD, free 25OHD has been reported to be more strongly associated with PTH, BMD and various non-skeletal or calcaemic outcomes (e.g. risk of various types of cancer) in some but not all reports. There is also conflicting evidence regarding racial differences in the total to free 25OHD ratio. These findings may be confounded by methodological issues in one of the DBP assays used, resulting in pronounced differences in DBP concentrations between GC-genotypes. I will review novel research into vitamin D and the current evidence regarding the potential differences between the relationships of free and total 25OHD with health outcomes and the potential role of DBP concentration and genotype.