Magnesium in Infectious Diseases in Older People

Abstract

Reduced magnesium (Mg) intake is a frequent cause of deficiency with age together with reduced absorption, renal wasting, and polypharmacotherapy. Chronic Mg deficiency may result in increased oxidative stress and low-grade inflammation, which may be linked to several age-related diseases, including higher predisposition to infectious diseases. Mg might play a role in the immune response being a cofactor for immunoglobulin synthesis and other processes strictly associated with the function of T and B cells. Mg is necessary for the biosynthesis, transport, and activation of vitamin D, another key factor in the pathogenesis of infectious diseases. The regulation of cytosolic free Mg in immune cells involves Mg transport systems, such as the melastatin-like transient receptor potential 7 channel, the solute carrier family, and the magnesium transporter 1 (MAGT1). The functional importance of Mg transport in immunity was unknown until the description of the primary immunodeficiency XMEN (X-linked immunodeficiency with Mg defect, Epstein-Barr virus infection, and neoplasia) due to a genetic deficiency of MAGT1 characterized by chronic Epstein-Barr virus infection. This and other research reporting associations of Mg deficit with viral and bacterial infections indicate a possible role of Mg deficit in the recent coronavirus disease 2019 (COVID-19) and its complications. In this review, we will discuss the importance of Mg for the immune system and for infectious diseases, including the recent pandemic of COVID-19.

Keywords: COVID-19; aging; infectious diseases; inflammation; magnesium; oxidative stress; vitamin D.

Figure 1

Mg and vitamin D metabolism. Vitamin D3 is produced in the skin through the action of UVB radiation reaching 7-dehydrocholesterol in the skin, followed by a thermal reaction. That vitamin D3 or oral vitamin D (D2 (ergocholecalciferol) or D3 (cholecalciferol) are converted to 25(OH)D in the liver and then to the active hormonal metabolite 1,25(OH)₂D (calcitriol) in the kidneys or other organs as needed. As shown in the graph, Mg is a cofactor that is required for the binding of vitamin D to its transport protein, for the conversion of vitamin D by hepatic 25-hydroxlation, for the transport of 25(OH)D, and for renal 1α-hydroxylation into the active hormonal form. Therefore, all these steps are Mg-dependent. DBP: vitamin D-binding protein.

Figure 2

Mg’s “calcium channel-blocking” effect, which can lead to the downstream suppression of NF-κB, IL-6 and may limit systemic inflammation. NF-kB: nuclear factor 70 kappa-light-chain-enhancer of activated B cells; IL-6: interleukin 6; CD4+: T helper cell; CD8+: cytotoxic T cell.

Figure 3

Active vitamin D (calcitriol or dihydroxycholecalciferol) helps maintain tight junctions, gap junctions, and adherens junctions in order to prevent the spread of SARS-CoV2 and induces the proliferation of macrophages and the release of cathelicidin and defensins, which are antimicrobial peptides active against a spectrum of microbes including viruses. Mg is a cofactor that is necessary for the synthesis, transport, and activation of vitamin D. ACE2: angiotensin-converting enzyme 2 receptor; DPP-4/CD26: dipeptidyl peptidase-4 receptor.

Figure 4

Proposed mechanisms by which vitamin D and Mg can exert actions against COVID-19. ACE, angiotensin-converting enzyme; ACE2: angiotensin-converting enzyme 2; Ang-(1-7), angiotensin (1-7); Ig, immunoglobulin; IFN-γ, interferon gamma; IL, interleukin; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; TNF-a, tumor necrosis factor alpha; Th, T helper cell; Treg, regulatory T cells.

Figure 5

Summary of Mg’s possible effects in COVID-19.