Vitamin D: not just the bone. Evidence for beneficial pleiotropic extraskeletal effects


Vitamin D is a fat-soluble vitamin and a steroid hormone that plays a central role in maintaining calcium-phosphorus and bone homeostasis in close interaction with parathyroid hormone, acting on its classical target tissues, namely, bone, kidney, intestine, and parathyroid glands. However, vitamin D endocrine system regulates several genes (about 3 % of the human genome) involved in cell differentiation, cell-cycle control, and cell function and exerts noncalcemic/pleiotropic effects on extraskeletal target tissues, such as immune and cardiovascular system, pancreatic endocrine cells, muscle, and adipose tissue. Several studies have demonstrated the role of vitamin D supplementation in the prevention/treatment of various autoimmune diseases and improvement of glucose metabolism, muscle, and adipose tissue function. Hence, this review aims to elucidate the effects of vitamin D on extraskeletal target tissues and to investigate the potential therapeutic benefit of vitamin D supplementation among a broad group of pathological conditions, especially with regard to metabolic and autoimmune diseases. In addition, we focused on the best daily intakes and serum levels of vitamin D required for extraskeletal benefits which, even if still controversial, appear to be higher than those widely accepted for skeletal effects.

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Fig. 1
Fig. 2


VD3 :

Vitamin D3



25(OH)D3 :

25-Hydroxyvitamin D3

1,25(OH)2D3 :

1,25-Dihydroxyvitamin D3


Vitamin D binding protein


Vitamin D receptor


Parathyroid hormone


Bone mineral density


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Caprio, M., Infante, M., Calanchini, M. et al. Vitamin D: not just the bone. Evidence for beneficial pleiotropic extraskeletal effects. Eat Weight Disord 22, 27–41 (2017).

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  • Autoimmune diseases
  • Hashimoto thyroiditis
  • Multiple sclerosis
  • Glucose metabolism
  • Adipose tissue
  • Obesity
  • Diabetes
  • Skeletal muscle
  • Eating disorders
  • Anorexia nervosa