Vitamin D Deficiency Increases Risk of Any Acute Respiratory Infection
And Vitamin D supplementation diminishes this risk and the risk of severe infection outcomes for persons with low baseline Vitamin D serum levels.
A systematic review of 38 studies (n = 207,587) found 7 studies demonstrating a statistically significant increased risk of infection and 16 studies demonstrating an increased risk of ICU admission and intubation following COVID19 infection from deficient calcifediol serum levels. 6 other studies including 2 cohorts, 2 clinical trials, 1 cross-sectional and 1 case control study found that calcifediol supplementation reduced the risk of ICU admission and intubation requirement by 62%. 7 demonstrated that calcifediol supplementation reduced the relative risk of COVID19 mortality by 65%. 9 retrospective and 10 prospective studies that measured the baseline calcifediol serum levels of COVID19 patients prior to infection demonstrated that deficient calcifediol serum levels double the risk of COVID19 mortality. A meta-analysis of 23 studies (n= 2,692) found that calcifediol serum deficiency doubled the relative risk of severe disease following SARS-COV-2 infection in 17 studies and mortality in 13 studies.
The elevated risks of infection and disease severity created by low vitamin D serum levels and the benefits of vitamin D supplementation extend well beyond SARS-COV-2 to other respiratory infections.
An individual participant data level meta-analysis of 25 RCTs (n = 10,933), published in the BMJ, found that vitamin D supplementation results in a statistically significant reduction in the proportion of participants experiencing at least one acute respiratory tract infection, which varied greatly depending on their baseline calcifediol serum levels. A subgroup analysis revealed that the strongest and only statistically significant effect for Vitamin D supplementation reducing the risk of any acute respiratory tract infection was at baseline levels lower than 25 nanomoles/liter or 10 ng/ml in 14 studies. A stratification of this subgroup analysis by dosing regimen revealed that daily or weekly Vitamin D supplementation was associated with an even greater protection against acute respiratory tract infection for participants above and below the 25 nmol/L baseline but had a stronger effect for those below the baseline.
A follow-up systematic review and meta-analysis, published in the Lancet, that included an additional 18 Vitamin D supplementation RCTs that measured the incidence of acute respiratory infections among participants prospectively (n = 48,488) between 2009 and 2021 found that a significantly lower proportion of participants taking a vitamin D supplement had one or more acute respiratory infections compared to placebo controls, but with no significant difference in the proportion of participants who had at least one acute respiratory infection between higher and lower doses. Vitamin D was only found to have a statistically significant protective effect, compared to placebo controls, as a daily regimen of 400-1,000 international units (10-25 ug) and not as a weekly or monthly bolus and not for participants with asthma or any lung disease.
As a 2013 review published in Nutrients notes, Vitamin D supports both the innate and adaptive immune system via the Vitamin D activating enzyme and vitamin D receptors on a variety of immunocytes that use circulating levels of calcitriol to suppress inflammatory cytokine response and regulate differentiation and proliferation of T and B cells and their subtypes. Thus, Vitamin D deficiency elevates the risk of hypercytokinemia and as I pointed out in a prior post dormant T cells naive to pathogens that invade the body constantly and thus not initiating a response from other immunocytes to the pathogens.