LAUSR

During my residency and training as an endocrinologist, I began to get interested in the study of vitamin D. In the past, vitamin D has been considered to be an essential vitamin for bone health but in recent years something has changed. I can affirm that there was a rediscovery of vitamin D; it is not just the Bbone vitamin^ but it has been shown to be a hormonewith several nonskeletal actions. The increased consensus on the pleiotropic effects of vitamin D and the high prevalence of hypovitaminosis D in the general healthy population have increased the interest in vitamin D among researchers, clinicians, and the lay public. Lack of vitamin D has been involved in the pathogenesis of several acute and chronic illnesses including musculoskeletal disorders [1], type 1 diabetes [2], type 2 diabetes [3], male hypogonadism [4], polycystic ovary syndrome (PCOS) [5], cancer [6], autism [7], dementia [8] and cardiovascular diseases [9]. Of particular interest is the possible involvement of vitamin D in the treatment of these diseases. Humans derive vitamin D from cutaneous synthesis (in the form of cholecalciferol (D3)), diet (in the form of D3), and nutritional supplements (in the form of D3) or ergocalciferol (D2) [10]. Upon exposure to ultraviolet B radiation (UVB), 7-dehydrocholesterol in the skin is converted to pre-vitamin D3, which is immediately converted to vitamin D3 in a heat-dependent process. After ingestion or synthesis, vitamin D is hydroxylated in the liver to form 25 hydroxyvitamin D (25(OH)D2 or 25(OH)D3, its major circulating form, which has little biological activity. 25(OH)D is converted in the kidney by 25(OH)D-1alpha-hydroxylase (CYP27B1), to its bioactive hormonal metabol i te 1 ,25 dihydroxy-vi tamin D (1,25(OH)2D or calcitriol). The primary action of 1,25(OH)2D is through the nuclear vitamin D receptor (VDR), which heterodimerizes with the retinoid X receptor and binds to vitamin D-responsive elements near target genes [10, 11]. The primary action of 1,25(OH)2D is to enhance intestinal calcium absorption and to promote osteoclast function, thereby keeping calcium and phosphorus homeostasis and bone health. However, the discovery that nearly all tissues in the body express the VDR and that several tissues also express CYP27B1, thereby allowing for local production of 1,25(OH)2D with a paracrine effect, has provided important insights into the pleiotropic effects of vitamin D and its potential role in a variety of extra-skeletal tissues [11]. There is no consensus on the 25(OH)D thresholds for defining vitamin D adequacy in order to prevent and/or treat chronic diseases. The only recommendations are related to skeletal outcomes. The guidelines by the Institute of Medicine (IOM) and the Endocrine Society differ on classification of vitamin D status [12, 13]. These differences are explained by the populations targeted by the guidelines and how the evidence was synthesized. Specifically, the IOM guidelines concentrated on the general healthy population and considered only trials, concluding that blood concentrations of 25(OH)D > 20 ng/ml are consistent with favorable skeletal outcomes. In contrast, the Endocrine Society clinical practice guidelines concentrated on people at high risk for vitamin D deficiency and considered both trials and observational (epidemiologic) studies in concluding that blood concentrations of 25(OH)D > 30 ng/ ml are desirable for optimal skeletal outcomes without any upper limit that would be concerning for safety. Based on this evidence, this guest issue was created with the aim to gather a selected international panel of independent scientific experts in order to develop a series of evidence-based reviews * Giovanna Muscogiuri [email protected]