Strengths and Limitations of Clinical Study Designs A daily dose of vitamin D may increase 25(OH)D with less diversion of 25(OH)D to 24,25(OH) 2D than bolus dosing.Ģ. A single high dose of vitamin D can induce the 24-hydroxylase enzyme (CYP24A1), resulting in greater production of 24,25(OH) 2D relative to 25(OH)D than daily supplementation. ĭaily or weekly doses of vitamin D, but not large bolus doses, were associated with a reduced risk of respiratory infection in a meta-analysis of randomized controlled trials of vitamin D supplementation, particularly in subjects with 25(OH)D values <25 nmol/L. Additionally, 1,25(OH)2D regulates ACE2 to reduce vascular sensitivity and SARS-CoV-2 attachment to ACE2 receptors. It also suppresses antigen presentation by dendritic cells and activation of T cells, thereby inhibiting proinflammatory cytokine production. Laboratory evidence demonstrates that 1,25(OH) 2D promotes the expression of antimicrobial proteins cathelicidin and β-defensin2 by pulmonary macrophages and epithelium. Specifically, vitamin D could have benefit in COVID-19 in three different ways: (1) reducing the risk of acquiring SARS-CoV-2 infection, (2) enhancing viral neutralization and clearance, and (3) reducing the severity of the inflammatory response. Vitamin D can alter the expression of genes involved in infection and inflammation and could theoretically decrease the severity of COVID-19 infection. ![]() All these cells express 1a-hydroxylase and are capable of locally producing 1,25(OH) 2D, which acts as an important immune and inflammatory modulator. There are three primary lung defenses against infection: airway epithelia, alveolar macrophages, and dendritic cells involved in cytokine production. Studies of vitamin D in COVID-19 are based on a biological rationale for the benefits of vitamin D in COVID-19. The COVID-19 pandemic continues, and current evidence for the role of vitamin D in the treatment and prevention of COVID-19 deserves regular review. The term COVID-associated acute respiratory distress syndrome (CARDS) has been used to describe the similar clinical manifestations and pathophysiology of severe COVID-19 and those of acute respiratory distress syndrome, including multisystemic effects from the release of proinflammatory cytokines. ![]() Severe COVID-19 results from an exuberant and dysregulated immune response to the SARS-CoV-2 virus. Local 1,25(OH) 2D enters the cell nucleus to influence the expression of genes, unrelated to calcium absorption or bone metabolism. Within these tissues, 1α-hydroxylase converts 25(OH)D to 1,25(OH) 2D in order to exert localized effects (paracrine effects), without altering serum 1,25(OH) 2D concentrations. Increasing interest in the non-skeletal effects of vitamin D relates to the finding of vitamin D receptors (VDR) widely distributed in most human tissues, as is the 1α-hydroxylase enzyme (CYP27B1). Vitamin D deficiency has classically been associated with the bone diseases of rickets in growing children and osteomalacia in adults. Theoretical Benefits of Vitamin D in COVID-19 Vitamin D doses greater than 100 mcg (4000 IU) daily should not be used without monitoring serum 25(OH)D and calcium.ġ. 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 may benefit those with mild or asymptomatic COVID-19, and those with greater 25(OH)D values may have lower risk of acquiring infection. Few RCTs of vitamin D supplementation have been completed, and they have shown no benefit of vitamin D in hospitalized patients. ![]() Serum 25(OH)D values >50 nmol/L have been associated with reduced infection rates, severity of COVID-19, and mortality in observational studies. bolus administration, interaction with other treatments, and timing of administration prior to or during the illness. However, any benefit of vitamin D in COVID-19 may be related to the dose, duration, daily vs. Randomized controlled trials (RCTs) overcome the problem of confounding, typically comparing outcomes between groups receiving vitamin D supplementation or placebo. Many conditions associated with low vitamin D status are also associated with worse COVID-19 outcomes. ![]() Observational studies typically assess the relationship of 25(OH)D values with COVID-19 outcomes. 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. 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.
0 Comments
Leave a Reply. |