Vitamin D high doses supplementation could represent a promising alternative to prevent or treat COVID-19 infection()

Although we lack enough evidence to justify supplementing with vitamin D in the prevention and treatment of COVID-19 infection, it is increasingly feasible that this hypothesis is valid. Two general underlying mechanisms should be considered. One would be the anti-infectious and immunomodulatory action that it exerts by improving intercellular barriers by stimulating innate immunity, as well as by modulating adaptive immunity. Also, vitamin D reduces the production of inflammatory cytokines, such as IL-2 and interferon-gamma (INFγ). More recently, multiple pleiotropic effects have been demonstrated on the actions of vitamin D at the anti-inflammatory and immunomodulatory level with positive results in studies with influenza, coronavirus, and other respiratory infections. An inverse relationship between serum vitamin D levels and the prevalence of the respiratory infectious disease has been described. Of interest, another mechanistic approach responds to considering the inhibition of the renin-angiotensin-aldosterone system (RAAS), which is exacerbated in COVID-19 infection because the virus binds to the enzyme ACE2, making more angiotensin II available to cause damage. Vitamin D inhibits mediators of RAAS – present in all cells of the body – and by inhibiting ACE activity and increasing ACE2, it lowers angiotensin II levels. We present studies with proposals for recommended doses of vitamin D, and although a single guideline is not specified, the possible benefits are promising. Finally, the purpose of this review is to share this idea with health professionals to ignite the debate and call for critical reflection, so that it can contribute to the undertaking of more and better clinical designs to validate the benefits of using high doses of vitamin D for the benefit of public health and especially in times of crisis for COVID-19.