Evaluating the Evidence in Clinical Studies of Vitamin D in COVID-19

Abstract

Laboratory evidence provides a biological rationale for the benefits of vitamin D in COVID-19, and vitamin D supplementation is associated with reduced risk of respiratory infections. Most of the clinical studies of vitamin D in COVID-19 have been observational, and the most serious problem with observational study design is that of confounding. Observational studies typically assess the relationship of 25(OH)D values with COVID-19 outcomes. Many conditions associated with low vitamin D status are also associated with worse COVID-19 outcomes. Randomized controlled trials (RCTs) overcome the problem of confounding, typically comparing outcomes between groups receiving vitamin D supplementation or placebo. However, any benefit of vitamin D in COVID-19 may be related to the dose, duration, daily vs. bolus administration, interaction with other treatments, and timing of administration prior to or during the illness. Serum 25(OH)D values >50 nmol/L have been associated with reduced infection rates, severity of COVID-19, and mortality in observational studies. Few RCTs of vitamin D supplementation have been completed, and they have shown no benefit of vitamin D in hospitalized patients. Vitamin D may benefit those with mild or asymptomatic COVID-19, and those with greater 25(OH)D values may have lower risk of acquiring infection. Because those at greatest risk of COVID-19 are also at greatest risk of vitamin D deficiency, it is reasonable to recommend vitamin D supplementation 15–20 mcg (600–800 IU) daily for the general population during the COVID-19 pandemic. Vitamin D doses greater than 100 mcg (4000 IU) daily should not be used without monitoring serum 25(OH)D and calcium.

Can vitamin D positively impact one or more postacute-COVID-19 syndrome musculoskeletal and cognitive complications?

“…56 As such, and although further well designed studies are warranted, available evidence suggests that efforts to maintain an optimal serum vitamin D status in the case of the COVID-19 patient may significantly reduce the risk of acute respiratory distress syndrome as well as its severity, with possible beneficial effects on the need for mechanical ventilation and/or intensive care unit admission. 57 As concluded by Thacher, 58 vitamin D may prove especially beneficial in those cases found to have mild or asymptomatic COVID-19. Because those at greatest risk of COVID-19 are also at greatest risk of vitamin D deficiency, Pal et al, 59 recommend that consideration be given to the administration of vitamin D supplements among the general population during the ongoing COVID-19 pandemic, and especially those who live in areas with high air pollution or where outdoor activity or sun exposure is limited.…”

Vitamin D deficiency in British South Asians, a persistent but avoidable problem associated with many health risks (including rickets, T2DM, CVD, COVID-19 and pregnancy complications): the case for correcting this deficiency

“…[61] Reduced pulmonary production of the angiotensin ll receptor [ANG2R] in ARDS is associated with poor outcomes but its secretion is increased specifically in the lungs by vitamin D while increased pulmonary ANG2R secretion is associated with reduction in the severity and a risks of ARDS experimentally. [62] The use of vitamin D 3 in Covid-19 illness has had little success in treatment, but it has usually been given in ever increasing bolus doses, [63,64] and large bolus doses are known to induce selfregulatory effects that reduce calcitriol formation and that persist for at least three months. [65] These effects include the reduction of hepatic 25 hydroxylation of vitamin-D and the stimulation of the secretion of fibroblast growth factor-23 [FGF-23] which is known to inhibit the action of the 1alpha-hydroxylase enzyme that activates 25[(OH)D to form calcitriol in both renal and non-renal target tissues.…”

COVID-19 at a Glance: An Up-to-Date Overview on Variants, Drug Design and Therapies

“…When the disease becomes severe, the new combination should prioritize targeting the cytokine storm [ 30 ]. Lastly, vitamin D supplementation has been suggested for the prevention and/or treatment of COVID-19 [ 31 ], because of its well-known immunomodulatory role. Another aspect of the current COVID-19 outbreak is the rise of germaphobes that rarely leave the house without a bottle of hand sanitizer.…”