Vitamin D supplementation: when and how?

The multiple effects of vitamin D on skeletal and extra-skeletal tissues increased the attention of scientists and public to the possible relationship between hypovitaminosis D and a variety of acute and chronic diseases. However, several points are still largely debated. In particular, the definition of optimal vitamin D status [as assessed by the circulating levels of 25-hydroxyvitamin D (25(OH)D)] remains controversial, and experts still disagree about several related outcomes: how to estimate the prevalence of vitamin D deficiency, when to start treatment, how to reach optimal 25(OH)D levels, which type of vitamin is preferable for supplementation, which dosing strategy is the better option. In this context, a matter of major debate is represented by the measurement of circulating level of 25(OH)D, whose determination is affected by the lack of standardization and by several technical problems. It has been recently hypothesized that free and bio-available, rather than total 25(OH)D, mostly determine its biological action. However, further evaluation of directly measured free 25(OH)D levels is needed, in order to establish its role in research and clinical practice. Finally, it is not yet defined if a threshold of optimal vitamin D status for reducing the risk of extra-skeletal diseases exists. Actually, it is plausible that the desired 25(OH)D level may vary widely, depending on the health outcome in question. However, this topic is uncertain, partly due to the lack of randomized controlled trials assessing the effect of vitamin D supplementation on extra-skeletal end-points.