Pleiotropic effects of vitamin D
Vitamin D is phylogenetically an old compound present in simple organisms without skeleton for millions of years. Its primary function, acting as a cytokine, has been the defence against microbial invaders. Vitamin D modulates the innate immune response by inducing the synthesis of endogenous antibiotics in monocytes-macrophages. Epithelial barrier tissues in lung, gut, placenta and skin employ the same antimicrobial mechanisms. Vitamin D also interacts with dendritic cells and lymphocytes to modulate the acquired immune response. Other important biological functions of vitamin D are the maintenance of muscle strength and size, stimulation of insulin production in β-cells, suppression of renin secretion from kidneys, attenuation of autoimmune inflammatory processes of atherogenesis in arterial wall. It can decrease cellular proliferation of both normal and cancer cells and induce their differentiation. The more advanced function of vitamin D is that of a hormone, reserved for species with endo-skeleton where it regulates calcium, phosphorus and bone homeostasis.
Vitamin D3 is metabolized in the liver to 25-OH vitamin D, which levels determine patients vitamin D status. 25-OH vitamin D is activated in kidneys to 1,25-(OH)2 vitamin D or hormone D that binds to its nuclear vitamin D receptor and controls more than 200 genes.
There is an epidemic of vitamin D deficiency (25-OH vitamin D less than 50 nmol/l) and insufficiency (25-OH vitamin D less than 75 nmol/l) in general population. Reasons are greater sun protection and increase in population body mass index. Severe vitamin D deficiency causes rickets or osteomalacia. Less severe forms have other serious consequences: increased risk of type I and type II diabetes, multiple sclerosis, rheumatoid arthritis, hypertension, cardiovascular disease, and cancer (colon, breast). Vitamin D insufficiency and deficiency are significantly associated with all-cause and cardiovascular mortality.
Optimal vitamin D levels are 75100 nmol/l. In the absence of sun exposure 1000 IU of cholecalciferol is required daily or 7000 IU weekly to maintain normal vitamin D levels. To achieve normal levels, 2000 IU daily are needed for a month or two. Vitamin D replacement is cheap and safe.