Effect of vitamin D deficiency in developed countries.

Introduction: Vitamin D deficiency is common worldwide with adverse effects on skeletal health. In recent years, there has been great interest in non-classical actions of vitamin D. Basic research has uncovered actions in a range of non-skeletal tissues, and observational studies have identified inverse relationships with risk of a number of disease states including sarcopenia, obesity, the metabolic syndrome, cardiovascular disease, cancer and autoimmune diseases. Sources of data: PubMed, Medline and Cochrane Systematic Reviews. Areas of agreement: Current evidence supports the use of vitamin D supplementation in deficiency to improve skeletal outcomes such as falls/fracture risk and bone mineral density. Areas of controversy: There is debate reflected in guidelines on optimal thresholds for circulating levels of vitamin D. Further studies are required to refine dosing regimens and treatment target levels of vitamin D. Growing points: A number of studies have investigated the extra-skeletal effects of vitamin D deficiency but causality in humans has yet to be confirmed. Areas timely for developing research: Large-scale randomized controlled trials incorporating data on vitamin D status at baseline and follow up, adverse events, and comparison of dosing regimens are required. It is imperative that studies are carried out with a diverse range of participants (age, gender and ethnicity), and settings to allow for a more individualized approach. In addition, we would advocate incorporating cutting-edge research tools into human studies to advance our understanding of the mechanisms of vitamin D action in extra-skeletal disease. This may involve multi-metabolite analysis of vitamin D metabolites, or unbiased approaches to assess regulation of gene/protein expression in tissues of interest.