Abstract
The vitamin D receptor is expressed in multiple cells of the body (other than osteoblasts), including beta cells and cells involved in immune modulation (such as mononuclear cells, and activated T and B lymphocytes), and most organs in the body including the brain, heart, skin, gonads, prostate, breast, and gut. Consequently, the extra-skeletal impact of vitamin D deficiency has been an active area of research. While epidemiological and case-control studies have often suggested a link between vitamin D deficiency and conditions such as type 1 and type 2 diabetes, connective tissue disorders, inflammatory bowel disorders, chronic hepatitis, food allergies, asthma and respiratory infections, and cancer, interventional studies for the most part have failed to confirm a causative link. This review examines available evidence to date for the extra-skeletal effects of vitamin D deficiency, with a focus on randomized controlled trials and meta-analyses.
Highlights
Given the extensive literature reported in this area over the last two decades, we have discussed key papers that illustrate variations in data reported from the various kinds of studies, with a focus on randomized controlled trials (RCTs) and meta-analyses of existing studies
Vitamin D passes into dermal capillaries and is carried by vitamin D binding protein (DBP) to the liver, where microsomal vitamin D 25-hydroxylase catalyzes its conversion to 25-hydroxy vitamin D [25(OH)D], the storage form of vitamin D. 25(OH)D is what is reported when we ask for levels of vitamin D, and most assays report both 25(OH)D2 and 25(OH)D3
D deficiency has been associated with conditions such as multiple sclerosis, type 1 diabetes (T1D), rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis, inflammatory bowel disease, hepatitis, asthma and respiratory infections
Summary
While the skeletal effects of vitamin D are well recognized and described extensively in the literature [1,2,3], its extra-skeletal effects have been subject to some controversy with conflicting data reported, for case-control or epidemiologic vs. prospective and interventional studies. This review aims to summarize and synthesize data regarding many extra-skeletal effects of vitamin D. Vitamin D3 (cholecalciferol) is synthesized primarily in the skin on exposure to ultraviolet radiation, while vitamin D2 (ergocalciferol) is derived from plant sources. Normative ranges for its possible extra-skeletal effects remain to be determined. Data suggest that vitamin D3 may be more effective in raising 25(OH)D levels than vitamin D2 (reviewed in [5]). 25(OH)D is transported to the kidney by DBP, where cytochromal 25-hydroxyvitamin D 1-α hydroxylase catalyzes its conversion to 1,25 dihydroxy vitamin D [1,25(OH) D], the active form of vitamin D. How vitamin D deficiency affects disease states in these multiple organ systems has been an active area of research. Repletion of vitamin D stores to mitigate and improve disease processes has been attempted in certain conditions, there is a paucity of data to direct clear treatment protocols, especially in the pediatric population
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