Magnesium Sulfate Supplementation in COVID-19

Magnesium, as an enzymatic activator, is essential for various physiological functions, such as the cell cycle, metabolic regulation, muscle contraction, and vasomotor tone. A growing body of evidence supports that magnesium supplementation (primarily magnesium sulfate and magnesium oxide) prevents or treats various types of disorders or diseases related to the respiratory system, reproductive system, nervous system, digestive system, and cardiovascular system, as well as kidney injury, diabetes, and cancer. In the current pandemic (COVID-19), characterized by respiratory tract symptoms with different degrees of significant organ and tissue damage, magnesium supplementation may be an interesting therapy. The possible existing mechanisms by which magnesium supplementation improves pulmonary symptoms and diseases are through anti-inflammation, antioxidation, and relaxation of bronchial smooth muscle.

Magnesium sulfate inhibits inflammatory molecules, including chemokine (macrophage inflammatory protein-2), cytokine (Interleukin-6, IL-6), prostaglandin E2, and cyclo-oxygenase-2 in lung tissue, possibly by inhibiting L-type calcium channels. In an acute lung injury model, magnesium sulfate ameliorates hydrochloric acid-induced pulmonary histopathology, including peribronchial inflammatory cell infiltration, alveolar septal infiltration, alveolar edema, and alveolar exudation. It also significantly restores oxidative stress and the inflammatory response in lipopolysaccharide-induced acute lung injury in mice. These observations demonstrate that magnesium has antioxidant and anti-inflammatory effects in lung injury. Magnesium sulfate also inhibits airway smooth muscle contraction by blocking voltage-dependent calcium channels, which is another mechanism of magnesium for the treatment of asthma. However, more detailed molecular mechanisms are still lacking.

Most patients with COVID-19 develop pneumonia accompanied by respiratory tract symptoms, including cough, sore throat, sputum production, hemoptysis, nasal congestion, dyspnea, and shortness of breath. The pathological features of COVID-19 show bilateral diffuse alveolar injury, and bilateral lung tissue exhibits inflammatory infiltration in patients with COVID-19. The elderly and people with underlying diseases are susceptible to infections and prone to severe consequences, even death, which may be associated with acute respiratory distress, potentially inducing an inflammatory response and cytokine storm, a strong release of proinflammatory cytokines IFN-γ, TNF-α, interleukin, and chemokines, which increase organ damage and accelerate the deterioration of the disease state. Magnesium sulfate, as a calcium antagonist, is commonly used to inhibit bronchial smooth muscle contraction and promote bronchodilation. It also decreases the inflammatory response and oxidative stress, as well as improves pulmonary inflammation, possibly by inhibiting the IL-6 pathway, the NF-κB pathway, and L-type calcium channels. Therefore, magnesium sulfate has good application prospects in controlling pulmonary symptoms.

Reference: Tang CF, Ding H, Jiao RQ, Wu XX, Kong LD. Possibility of magnesium supplementation for supportive treatment in patients with COVID-19. Eur J Pharmacol. 2020;886:173546. doi:10.1016/j.ejphar.2020.173546

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