inflammation flow chart

Vitamin D and immunity

Vitamin D can be synthesized in the skin when it is exposed to sunlight and is then metabolized in the liver and kidney to the metabolically active form called 1α,25-dihydroxyvitamin D. Through binding to the vitamin D receptor (VDR), 1α,25-dihydroxyvitamin D can regulate the expression of hundreds of genes involved in skeletal and other biological functions (1). Vitamin D exhibits many non-skeletal effects, particularly on the immune system.

Acting through the VDR, 1α,25-dihydroxyvitamin D is a potent immune system modulator. The VDR is expressed by most cells of the immune system, including regulatory T cells and antigen-presenting cells, such as dendritic cells and macrophages. Under specific circumstances, monocytes, macrophages, and T cells can express the 25-hydroxyvitamin D3-1α-hydroxylase enzyme and produce 1α,25-dihydroxyvitamin D, which acts locally to regulate the immune response (2,3). There is considerable scientific evidence that 1α,25-dihydroxyvitamin D has a variety of effects on immune system function, which may enhance innate immunity and inhibit the development of autoimmunity. Conversely, vitamin D deficiency may compromise the integrity of the immune system and lead to inappropriate immune responses.

More than 200 viruses are responsible for causing familiar infections of the upper respiratory tract (URT), known as the common cold, resulting in symptoms of nasal congestion and discharge, cough, sore throat, and sneezing. The analysis of cross-sectional data from 18,883 participants (ages 12 years and older) of the Third US National Health and Nutrition Examination Survey (NHANES III) reported an inverse relationship between serum 25-hydroxyvitamin D concentrations and recent (self-reported) URT infection (URTI). Compared to levels of circulating vitamin D of 30 ng/mL or above, the risk of URTI was 24% higher in individuals with concentrations between 10 and 29 ng/mL and 36% higher in those with levels below 10 ng/mL (5).

Vitamin D deficiency in pregnancy may cause early asthma and wheezing, since vitamin D has effects on the developing lung and immune system during the fetal and early postnatal periods. Other randomized control trials indicated that vitamin D3 supplementation during pregnancy decreased the rate of respiratory tract infections or wheeze within the first 5 years of infant’s life (4).

At sufficient UV-B exposure, humans can synthesize vitamin D3 endogenously in their skin. However, today’s lifestyle often makes the molecule a true vitamin and micronutrient that needs to be taken up by diet or supplementation especially for immune-supportive benefits.


  2. Edfeldt K, Liu PT, Chun R, et al. T-cell cytokines differentially control human monocyte antimicrobial responses by regulating vitamin D metabolism. Proc Natl Acad Sci U S A. 2010;107(52):22593-22598.
  3. Smolders J, Thewissen M, Damoiseaux J. Control of T cell activation by vitamin D. Nat Immunol. 2011;12(1):3; author reply 3-4.
  4. Wagner and Hollis (2018) The implications of vitamin D status during pregnancy on mother and her developing child. Frontiers in Endocrinology. 9:500
  5. Ginde et al (2009) Association between serum 25-hydroxyvitamin D levels and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Archives of internal medicine. 169(4):384-390