A New Approach to Infection: Vitamin D

Vitamin D has a role in the immune system distinct from its regulatory role in calcium homeostasis. Immune cells express the vitamin D receptor and can metabolize circulating 25-hydroxyvitamin D into its active form, 1,25-dihydroxyvitamin D. This finding has researchers looking for new ways to manipulate vitamin D in the innate and adaptive immune systems.

Humans have used Vitamin D throughout time to treat illness. Physicians prescribed cod liver oil and sunlight to treat infection for years before effective antibiotics were discovered, unaware that the apparent active ingredient in both is vitamin D. Vitamin D is heralded mostly for its role in bone health, but it also has a role in the immune system distinct from its regulatory role in calcium homeostasis. Immune cells express the vitamin D receptor and can metabolize circulating 25-hydroxyvitamin D into its active form, 1,25-dihydroxyvitamin D. This finding has researchers looking for new ways to manipulate vitamin D in the innate and adaptive immune systems.

The December 2014 issue of Current Opinion in Endocrinology, Diabetes, and Obesity includes an article that describes this vitamin’s exciting possibilities in infectious disease. The authors ask: Might vitamin D modulate inflammatory response and autoimmune disease? The hypothesis that it may be beneficial is based on studies associating low vitamin D levels with a number of infectious diseases including respiratory infection, septic shock, and influenza.

The authors concisely summarize current knowledge. Salient points include the following:

  • 1,25-dihydroxyvitamin D has been shown to trigger antimicrobial peptide production with a direct pathogen-killing capacity.
  • Vitamin D signaling is linked to human innate immune response.
  • Various cells, including monocytes and macrophages, express CYP27B1, the enzyme responsible for the final step in the conversion of 25(OH)D3 into bioactive 1,25(OH)2D3.
  • In respiratory epithelial cells, 1,25(OH)2D3 appears to enhance killing of airway pathogens, such as Bordetella bronchiseptica and Pseudomonas aeruginosa.

Clinically, vitamin D’s role in infectious disease has numerous clinical implications. Tuberculosis (TB) appears to develop more ready in vitamin D-deficient individuals. Studies have produced mixed results when they have administered vitamin D to TB patients—some show increased response to medication while others do not. Some researchers believe that in TB, patients need low doses of vitamin D for long periods of time as opposed to short bouts of high-dose therapy.

Isolated vitamin D studies have also shown beneficial results in preventing influenza in children.

Future studies need to look for ideal doses and dosing regimens, and investigate subgroups that may be more responsive to vitamin D.