Re: Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials
Vitamin D can be synthesized by human skin from 7-dehydrocholesterol with the help of ultraviolet light obtained from sunlight. Calcitriol is the active form of vitamin D which is formed after two hydroxylation reactions; one at 25th position occurs in liver by 25-α-hydroxylase and the other in kidney at 1st position by 1-α-hydroxylase enzymes. The presence of extra renal 1-α-hydroxylase enzyme in many tissues including macrophages, B cells and T cells has led to the proposal that vitamin D also play important role in these tissues. 25-hydroxy vitamin D is the major circulating form of vitamin D and the extra renal tissues convert it into calcitriol where it acts in a paracrine manner.
As a result of this, many disease conditions including autoimmune diseases, infectious diseases including HIV, type 2 diabetes and metabolic syndrome and some types of cancers are associated with low serum levels of 25-hyroxy vitamin D. In these conditions, whether decreased 25-hydroxy vitamin D in serum is the cause or effect is debatable. The role of vitamin D in modulating the immune responses involves production of calcitriol by extra renal 1-α-hydroxylase enzyme acting on 25-hydroxy vitamin D obtained possibly from plasma. This could possibly explain the decreased level of 25-hydroxy vitamin D observed in the plasma of patients with various diseases. Supplementing vitamin D in such cases would then depend on the effect of vitamin D in the overall disease process. The overall effect of vitamin D may be even more complicated in inflammatory conditions in metabolically active tissues such as adipose tissue. Since inflammation is one of the common events observed in many of the clinical outcomes studied, it is very important that future research on vitamin D should be conducted to decipher the effects of vitamin D in mediating both immune and metabolic functions.
Lastly, a deeper understanding of the vitamin D metabolism and better biomarker to assess its deficiency are needed.
Competing interests: No competing interests