Vitamin D: Why I Think it’s Anti-viral

When I wrote my initial blog entry, I realized that there wasn’t direct evidence for its application for prevention or mitigation of COVID-19, and this has been pointed out to me by three people. Nevertheless, I think that vitamin D is likely to be anti-viral because (a) of circumstantial evidence correlating vitamin D deficiency with viral infections, (b) an immunological role of vitamin D and (c) new trials to directly test vitamin D against SARS-CoV2.

(a) Circumstantial evidence. There are many studies that have shown that viral infections are more frequent and severe in the presence of poor vitamin D status. As early as 1979 a strong association between “colds” and rickets (frank vitamin D deficiency) was reported among children. In a survey (published in 2009) of over 18000 individuals in the USA between 1988 and 1994, there was a correlation between serum levels of 25-OH vitamin D3 (25-OHD3, the standard marker for vitamin D status) and upper respiratory tract infections. A more recent review in 2015 (Can J Physiol Pharmacol 93(5):363-8) updated the association between vitamin D deficiency and the increased risk of acquiring various infections.

In the specific case of COVID-19, it started in China in mid-winter when vitamin D status is at its worst. This viral infection has been a lesser problem to date in the southern hemisphere, notably New Zealand and Australia, where it was summer when it started to spread internationally. The evidence associating vitamin D deficiency and increased COVID-19 severity includes a May 2020 publication by Ilie et al who reviewed a number of European studies for which the incidence of the disease and blood levels of 25-OHD3 were available. They found a correlation between vitamin D deficiency and the numbers of both cases and deaths due to COVID-19; there was a statistically significant downward slope showing fewer cases and deaths with higher 25-OHD3 levels. Examples of factors that result in low serum 25-OHD3 concentrations were given as avoidance of sunlight and more skin pigmentation by people in southern Europe. Higher amounts of serum 25-OHD3 in northern countries was attributed to fortification of food with vitamin D and consumption of cod liver oil and vitamin D supplements. (Ilie, P.C., Stefanescu, S. & Smith, L. The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality. Aging Clin Exp Res (2020). https://doi.org/10.1007/s40520-020-01570-8) Somali immigrants in Sweden are 10-fold over represented as victims of COVID-19. While there are socio-economic explanations for this, their more extensive skin pigmentation puts them at risk for vitamin D deficiency. Similarly in the United States the order of vitamin D deficiency in racial groups is Blacks, Hispanics, Whites, which is the same order as deaths rates due to COVID-19.

(b) Immunological role. It is now widely accepted that vitamin D is essential for proper immunological functions. In a comprehensive discussion of vitamin D and viral infections, Teymoori-Rad et al (2019) describe the vitamin D-induced formation of cathelicidin and βdefensin. They address mechanisms by which these peptides might exert anti-viral activity as well as mechanisms by which vitamin D could interfere with the “cytokine storm” associated with severe viral infections including that of COVID-19. (Majid Teymoori‐Rad, Fazel Shokri,Vahid Salimi, Sayed Mahdi Marashi. The interplay between vitamin D and viral infections. Reviews in Medical Virology March 2019, Volume 29(Issue2) 16 pages.)

The role of vitamin D in immune function is just one of several that have been added to the classical bone calcium effect. Due to these many functions it is referred to as a hormone rather than a vitamin. Nevertheless there is one striking difference between vitamin D and classical hormones such as insulin. Vitamin D release in the body is not regulated by negative feedback. In the case of insulin, lower blood sugar results in decreased insulin release.