The vitamin D endocrine system (D-endo) is essential for calcium and bone homeostasis. The vitamin D receptor, VDR, is ubiquitously expressed and about 3% of the mouse or human genome is regulated by D-endo. VDR knock-out mice show impaired striated muscle maturation and selective VDR deficiency in heart muscle cause cardiomyopathy. Muscle weakness may be severe in patients with severe chronic renal failure combined with vitamin D deficiency or in subjects with congenital CYP27B1 deficiency. Muscle strength and function may be impaired in elderly vitamin D deficient elderly subjects and result in increased risks of falls. The final proof of causality is hotly debated but meta-analyses of supplementation studies suggest a modest reduction in falls in elderly subjects with severe vitamin D deficiency. All cells of the immune system express VDR. A large number of immune-related genes are coherently controlled by 1,25(OH)2D. The native immune system is stimulated by 1,25(OH)2D. A low vitamin D status is associated with an increased risk for all types of infections. Human intervention studies however are equivocal. The acquired immune system is suppressed by D-endo. In animal models vitamin D deficiency leads to increased sensitivity to autoimmune diseases such as inflammatory bowel disease or autoimmune diabetes after exposure to predisposing factors. In man, epidemiological studies confirm such associations, but intervention studies till now fail to show preventive effects. The antiproliferative effect of 1,25(OH)2D on cancer cells has been confirmed in most cells with inhibition of the cell cycle. VDR deficient mice are more prone to cancer when exposed to predisposing factors. The association between a low vitamin D status and colon cancer is fairly consistent in several meta-analyses. A few RCTs however have so far not confirmed beneficial effects on caner. In conclusion, serum 25OHD levels above 20 ng/ml may convey some global health benefits beyond bone but ongoing studies will allow confirming or correcting this conclusion.
20 - 23 May 2017
European Society of Endocrinology