Vitamin D assay and supplementation: still debatable issues.

Over the last decades, in addition to the improvement of pathophysiological knowledge regarding the role and mechanisms of action of vitamin D, there has been a progressive advancement in analytical technologies for its measurement, as well as in methodological standardization. A significant number of scientific works, meta-analyses, and guidelines have been published on the importance of vitamin D and the need for supplementation in deficient individuals. However, it appears necessary to clarify the fundamental elements related to the measurement of vitamin D (both at the strictly analytical and post-analytical levels) and the scientific evidence related to the efficacy/safety of supplementation. In particular, there is a need to discuss current recommended levels for deficiency, insufficiency and possible toxicity in the light of evidence from standardization projects. Additionally, given the important interrelations between vitamin D, parathyroid hormone (PTH), and fibroblast growth factor-23 (FGF23), the analytical issues and clinical utility of these biomarkers will be discussed.