The possible double-edged sword effects of vitamin D on COVID-19: A hypothesis

Cell Biol Int. 2021 Jan;45(1):54-57. doi: 10.1002/cbin.11469. Epub 2020 Oct 10.


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) gains access to host cells by attaching to angiotensin-converting enzyme 2 (ACE2). Vitamin D (VitD) can upregulate ACE2 and has an antagonistic effect on Renin, which exerts a vasodilatation and anti-inflammatory effect against coronavirus disease (COVID-19). However, it may also facilitate viral entry by increasing ACE2 as the main SARS-CoV-2 receptor and mediates ROS production through NADPH oxidase, as a double-edged sword effect. Lung function and the immune system are also influenced by VitD through several mechanisms, including increased natural antibiotics (Defensin and Cathelicidin) and upregulated transforming growth factor-β. A higher IgA, Th2/Th1 ratio, and T-regulatory cells are attributable to VitD effects on the immune cells, while these changes may also be a double-edged sword in COVID-19. Although VitD supplementation might be highly recommended in COVID-19, the administration's dosage and route could be challenging. Furthermore, this issue has not been mentioned in various studies so far. So, the report aimed to explain the current challenges with the application of VitD in COVID-19.

Keywords: COVID-19; angiotensin-converting enzyme 2; receptor; severe acute respiratory syndrome; supplementation; vitamin D.

Publication types

  • Review

MeSH terms

  • Angiotensin-Converting Enzyme 2 / metabolism*
  • Animals
  • COVID-19 / metabolism*
  • COVID-19 Drug Treatment
  • Humans
  • Treatment Outcome
  • Vitamin D / administration & dosage*
  • Vitamin D / metabolism*
  • Vitamin D Deficiency / drug therapy
  • Vitamin D Deficiency / metabolism*


  • Vitamin D
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2