Antioxidant/anti‐inflammatory effect of Mg²⁺ in coronavirus disease 2019 (COVID‐19)

Abstract

Severe acute respiratory syndrome coronavirus type 2 (SARS‐CoV‐2) causes coronavirus disease 2019 (COVID‐19), characterised by high levels of inflammation and oxidative stress (OS). Oxidative stress induces oxidative damage to lipids, proteins, and DNA, causing tissue damage. Both inflammation and OS contribute to multi‐organ failure in severe cases. Magnesium (Mg 2+ ) regulates many processes, including antioxidant and anti‐inflammatory responses, as well as the proper functioning of other micronutrients such as vitamin D. In addition, Mg 2+ participates as a second signalling messenger in the activation of T cells. Therefore, Mg 2+ deficiency can cause immunodeficiency, exaggerated acute inflammatory response, decreased antioxidant response, and OS. Supplementation with Mg 2+ has an anti‐inflammatory response by reducing the levels of nuclear factor kappa B (NF‐κB), interleukin (IL) ‐6, and tumor necrosis factor alpha. Furthermore, Mg 2+ supplementation improves mitochondrial function and increases the antioxidant glutathione (GSH) content, reducing OS. Therefore, Mg 2+ supplementation is a potential way to reduce inflammation and OS, strengthening the immune system to manage COVID‐19. This narrative review will address Mg 2+ deficiency associated with a worse disease prognosis, Mg 2+ supplementation as a potent antioxidant and anti‐inflammatory therapy during and after COVID‐19 disease, and suggest that randomised controlled trials are indicated.

Glutathione deficiency in the pathogenesis of SARS-CoV-2 infection and its effects upon the host immune response in severe COVID-19 disease

“…The demonstration that a combination of glycine and N-acetylcysteine supplementation rapidly improves GSH deficiency, oxidative stress and oxidant damage has implications for considering the GSH importance in combating COVID-19 infected patients warranting further investigations ( Kumar P. et al, 2022 ). Enzymes involved in GSH biosynthesis and function like γ-glutamyl-cysteine ligase and glutathione synthetase are completely dependent on ATP and require magnesium as a cofactor ( Bani Younes et al, 2020 ; Tang et al, 2020 ; Arancibia-Hernández et al, 2022 ). Additionally, γ-glutamyl-transpeptidase uses magnesium as an enzyme activator ( Arancibia-Hernández et al, 2022 ).…”

“…Enzymes involved in GSH biosynthesis and function like γ-glutamyl-cysteine ligase and glutathione synthetase are completely dependent on ATP and require magnesium as a cofactor ( Bani Younes et al, 2020 ; Tang et al, 2020 ; Arancibia-Hernández et al, 2022 ). Additionally, γ-glutamyl-transpeptidase uses magnesium as an enzyme activator ( Arancibia-Hernández et al, 2022 ). Magnesium supplementation improves mitochondrial function and increases the content of GSH in those organelles ( Liu et al, 2019 ; Mohammadi et al, 2020 ).…”

“…Magnesium supplementation improves mitochondrial function and increases the content of GSH in those organelles ( Liu et al, 2019 ; Mohammadi et al, 2020 ). Furthermore, magnesium sulfate was effective as a treatment for preeclampsia, significantly promoting GSH production and suppressing ROS generation ( Kawasaki et al, 2019 ; Arancibia-Hernández et al, 2022 ). Recent studies have suggested that serum magnesium levels of critically ill patients deserve attention ( Bani Younes et al, 2020 ; Iotti et al, 2020 ) and could not only prevent SARS CoV-2 infection, reduce severity of COVID-19 symptoms and facilitate disease recovery ( Trapani et al, 2022 ) but benefit enzymatic activity of the GSH pathway in COVID-19.…”

The Significance of Low Magnesium Levels in COVID-19 Patients

“…Endothelial dysfunction and procoagulant status may explain the high incidence of thromboembolic events in patients with COVID-19 [ 72 , 84 , 85 ]. Magnesium deficits exacerbate the inflammatory response induced by SARS-CoV-2 and maintain and propagate the so-called cytokine storm, followed by acute respiratory distress syndrome, which favors the development of endothelial lesions and coagulopathy, the consequence of which is multiple organ dysfunction syndrome [ 84 , 85 , 89 ]. In addition, other symptoms that have been reported by patients with COVID-19, such as asthenia, myalgias, anxiety, depression, and insomnia, may be related to the presence of a Mg 2+ deficiency [ 84 , 90 , 91 ].…”

“…The SHADE study [ 101 ] revealed that a higher proportion of vitamin D-deficient individuals with SARS-CoV-2 infection became SARS-CoV-2 RNA negative, with a significant decrease in the inflammatory marker (fibrinogen) on short-term, high-dose cholecalciferol supplements. Furthermore, it has been observed that concomitant supplementation with vitamin D, vitamin B12, and Mg 2+ in patients with COVID-19 may decrease the incidence of intensive care hospitalization and required oxygen therapy [ 89 , 102 ].…”