A potential protective role of magnesium in neuroCOVID

Several recent studies support a role of dysregulated magnesium homeostasis in COVID-19. In the present narrative review, we focus on the neurological aspects of this disease, collectively known as neuroCOVID, and we propose some mechanisms by which alterations of magnesium may contribute to the involvement of the nervous system in the context of SARS-CoV-2 infection. Further fundamental, translational, and clinical research is needed to underpin the potential relationships between altered magnesium status and neuro-COVID, with potentially novel therapeutic implications.

Essential sufficiency of zinc, ω-3 polyunsaturated fatty acids, vitamin D and magnesium for prevention and treatment of COVID-19, diabetes, cardiovascular diseases, lung diseases and cancer.

Despite the development of a number of vaccines for COVID-19, there remains a need for prevention and treatment of the virus SARS-CoV-2 and the ensuing disease COVID-19. This report discusses the key elements of SARS-CoV-2 and COVID-19 that can be readily treated: viral entry, the immune system and inflammation, and the cytokine storm. It is shown that the essential nutrients zinc, ω-3 polyunsaturated fatty acids (PUFAs), vitamin D and magnesium provide the ideal combination for prevention and treatment of COVID-19: prevention of SARS-CoV-2 entry to host cells, prevention of proliferation of SARS-CoV-2, inhibition of excessive inflammation, improved control of the regulation of the immune system, inhibition of the cytokine storm, and reduction in the effects of acute respiratory distress syndrome (ARDS) and associated non-communicable diseases. It is emphasized that the non-communicable diseases associated with COVID-19 are inherently more prevalent in the elderly than the young, and that the maintenance of sufficiency of zinc, ω-3 PUFAs, vitamin D and magnesium is essential for the elderly to prevent the occurrence of non-communicable diseases such as diabetes, cardiovascular diseases, lung diseases and cancer. Annual checking of levels of these essential nutrients is recommended for those over 65 years of age, together with appropriate adjustments in their intake, with these services and supplies being at government cost. The cost:benefit ratio would be huge as the cost of the nutrients and the testing of their levels would be very small compared with the cost savings of specialists and hospitalization.

Cohort study to evaluate the effect of vitamin D, magnesium, and vitamin B12 in combination on progression to severe outcomes in older patients with coronavirus (COVID-19).

OBJECTIVES: The aim of this study was to determine clinical outcomes of older patients with coronavirus (COVID-19) who received a combination of vitamin D, magnesium, and vitamin B12 (DMB) compared with those who did not. We hypothesized that fewer patients administered this combination would require oxygen therapy, intensive care support, or a combination of both than those who did not. METHODS: This was a cohort observational study of all consecutive hospitalized patients ≥50 y of age with COVID-19 in a tertiary academic hospital. Before April 6, 2020, no patients received the (DMB) combination. After this date, patients were administered 1000 IU/d oral vitamin D3, 150 mg/d oral magnesium, and 500 mcg/d oral vitamin B12 upon admission if they did not require oxygen therapy. Primary outcome was deterioration leading to any form of oxygen therapy, intensive care support, or both. RESULTS: Between January 15 and April 15, 2020, we identified 43 consecutive patients ≥50 y of age with COVID-19. Seventeen patients received DMB before onset of primary outcome and 26 patients did not. Baseline demographic characteristics between the two groups were significantly different by age. In univariate analysis, age and hypertension had a significant influence on outcome. After adjusting for age or hypertension separately in a multivariate analysis, the intervention group retained protective significance. Fewer treated patients than controls required initiation of oxygen therapy during hospitalization (17.6 vs 61.5%, P = 0.006). DMB exposure was associated with odds ratios of 0.13 (95% confidence interval [CI], 0.03-0.59) and 0.20 (95% CI, 0.04-0.93) for oxygen therapy, intensive care support, or both on univariate and multivariate analyses, respectively. CONCLUSIONS: A vitamin D / magnesium / vitamin B12 combination in older COVID-19 patients was associated with a significant reduction in the proportion of patients with clinical deterioration requiring oxygen support, intensive care support, or both. This study supports further larger randomized controlled trials to ascertain the full benefit of this combination in ameliorating the severity of COVID-19.

Magnesium and Vitamin D Deficiency as a Potential Cause of Immune Dysfunction, Cytokine Storm and Disseminated Intravascular Coagulation in covid-19 patients.

Magnesium and vitamin D each have the possibility of affecting the immune system and consequently the cytokine storm and coagulation cascade in COVID-19 infections. Vitamin D is important for reducing the risk of upper respiratory tract infections and plays a role in pulmonary epithelial health. While the importance of vitamin D for a healthy immune system has been known for decades, the benefits of magnesium has only recently been elucidated. Indeed, magnesium is important for activating vitamin D and has a protective role against oxidative stress. Magnesium deficiency increases endothelial cell susceptibility to oxidative stress, promotes endothelial dysfunction, reduces fibrinolysis and increases coagulation. Furthermore, magnesium deficient animals and humans have depressed immune responses, which, when supplemented with magnesium, a partial or near full reversal of the immunodeficiency occurs. Moreover, intracellular free magnesium levels in natural killer cells and CD8 killer T cells regulates their cytotoxicity. Considering that magnesium and vitamin D are important for immune function and cellular resilience, a deficiency in either may contribute to cytokine storm in the novel coronavirus 2019 (COVID-19) infection.

Possibility of magnesium supplementation for supportive treatment in patients with COVID-19.

Magnesium as an enzymatic activator is essential for various physiological functions such as cell cycle, metabolic regulation, muscle contraction, and vasomotor tone. A growing body of evidence supports that magnesium supplementation (mainly magnesium sulfate and magnesium oxide) prevents or treats various types of disorders or diseases related to respiratory system, reproductive system, nervous system, digestive system, and cardiovascular system as well as kidney injury, diabetes and cancer. The ongoing pandemic coronavirus disease 19 (COVID-19) characterized by respiratory tract symptoms with different degrees of important organ and tissue damages has attracted global attention. Particularly, effective drugs are still lacking in the COVID-19 therapy. In this review, we find and summarize the effectiveness of magnesium supplementation on the disorders or diseases, and provide a reference to the possibility of magnesium supplementation for supportive treatment in patients with COVID-19.

SARS-CoV-2: influence of phosphate and magnesium, moderated by vitamin D, on energy (ATP) metabolism and on severity of COVID-19.

The use of vitamin D to reduce the severity of COVID-19 complications is receiving considerable attention, backed by encouraging data. Its purported mode of action is as an immune modulator. Vitamin D, however, also affects the metabolism of phosphate and Mg, which may well play a critical role in SARS-CoV-2 pathogenesis. SARS-CoV-2 may induce a cytokine storm that drains ATP whose regeneration requires phosphate and Mg. These minerals, however, are often deficient in conditions that predispose people to severe COVID-19, including older age (especially males), diabetes, obesity, and usage of diuretics. Symptoms observed in severe COVID-19 also fit well with those seen in classical hypophosphatemia and hypomagnesemia, such as thrombocytopenia, coagulopathy, dysfunction of liver and kidneys, neurologic disturbances, immunodeficiency, failure of heart and lungs, delayed weaning from a respirator, cardiac arrhythmia, seizures, and, finally, multiorgan failure. Deficiencies of phosphate and Mg can be amplified by kidney problems commonly observed in patients with COVID-19 resulting in their wastage into urine. Available data show that phosphate and Mg are deficient in COVID-19, with phosphate showing a remarkable correlation with its severity. In one experiment, patients with COVID-19 were supplemented with a cocktail of vitamin D3, Mg, and vitamin B12, with very encouraging results. We, thus, argue that patients with COVID-19 should be monitored and treated for phosphate and Mg deficiencies, ideally already in the early phases of infection. Supplementation of phosphate and Mg combined with vitamin D could also be implemented as a preventative strategy in populations at risk.

Relationships between hyperinsulinaemia, magnesium, vitamin D, thrombosis and COVID-19: rationale for clinical management.

Risk factors for COVID-19 patients with poorer outcomes include pre-existing conditions: obesity, type 2 diabetes mellitus, cardiovascular disease (CVD), heart failure, hypertension, low oxygen saturation capacity, cancer, elevated: ferritin, C reactive protein (CRP) and D-dimer. A common denominator, hyperinsulinaemia, provides a plausible mechanism of action, underlying CVD, hypertension and strokes, all conditions typified with thrombi. The underlying science provides a theoretical management algorithm for the frontline practitioners.Vitamin D activation requires magnesium. Hyperinsulinaemia promotes: magnesium depletion via increased renal excretion, reduced intracellular levels, lowers vitamin D status via sequestration into adipocytes and hydroxylation activation inhibition. Hyperinsulinaemia mediates thrombi development via: fibrinolysis inhibition, anticoagulation production dysregulation, increasing reactive oxygen species, decreased antioxidant capacity via nicotinamide adenine dinucleotide depletion, haem oxidation and catabolism, producing carbon monoxide, increasing deep vein thrombosis risk and pulmonary emboli. Increased haem-synthesis demand upregulates carbon dioxide production, decreasing oxygen saturation capacity. Hyperinsulinaemia decreases cholesterol sulfurylation to cholesterol sulfate, as low vitamin D regulation due to magnesium depletion and/or vitamin D sequestration and/or diminished activation capacity decreases sulfotransferase enzyme SULT2B1b activity, consequently decreasing plasma membrane negative charge between red blood cells, platelets and endothelial cells, thus increasing agglutination and thrombosis.Patients with COVID-19 admitted with hyperglycaemia and/or hyperinsulinaemia should be placed on a restricted refined carbohydrate diet, with limited use of intravenous dextrose solutions. Degree/level of restriction is determined by serial testing of blood glucose, insulin and ketones. Supplemental magnesium, vitamin D and zinc should be administered. By implementing refined carbohydrate restriction, three primary risk factors, hyperinsulinaemia, hyperglycaemia and hypertension, that increase inflammation, coagulation and thrombosis risk are rapidly managed.

Combating COVID-19 and Building Immune Resilience: A Potential Role for Magnesium Nutrition?

Background: In December 2019, the viral pandemic of respiratory illness caused by COVID-19 began sweeping its way across the globe. Several aspects of this infectious disease mimic metabolic events shown to occur during latent subclinical magnesium deficiency. Hypomagnesemia is a relatively common clinical occurrence that often goes unrecognized since magnesium levels are rarely monitored in the clinical setting. Magnesium is the second most abundant intracellular cation after potassium. It is involved in >600 enzymatic reactions in the body, including those contributing to the exaggerated immune and inflammatory responses exhibited by COVID-19 patients.Methods: A summary of experimental findings and knowledge of the biochemical role magnesium may play in the pathogenesis of COVID-19 is presented in this perspective. The National Academy of Medicine's Standards for Systematic Reviews were independently employed to identify clinical and prospective cohort studies assessing the relationship of magnesium with interleukin-6, a prominent drug target for treating COVID-19.Results: Clinical recommendations are given for prevention and treatment of COVID-19. Constant monitoring of ionized magnesium status with subsequent repletion, when appropriate, may be an effective strategy to influence disease contraction and progression. The peer-reviewed literature supports that several aspects of magnesium nutrition warrant clinical consideration. Mechanisms include its "calcium-channel blocking" effects that lead to downstream suppression of nuclear factor-Kß, interleukin-6, c-reactive protein, and other related endocrine disrupters; its role in regulating renal potassium loss; and its ability to activate and enhance the functionality of vitamin D, among others.Conclusion: As the world awaits an effective vaccine, nutrition plays an important and safe role in helping mitigate patient morbidity and mortality. Our group is working with the Academy of Nutrition and Dietetics to collect patient-level data from intensive care units across the United States to better understand nutrition care practices that lead to better outcomes.